Print Page | Close Window

OPEN ACCESS links, articles, TNBC

Printed From: TNBC Foundation
Category: TNBC Forums
Forum Name: Welcome New Members
Forum Description: A place to introduce yourself to our community
URL: http://forum.tnbcfoundation.org/forum_posts.asp?TID=9440
Printed Date: Apr 23 2019 at 6:57pm
Software Version: Web Wiz Forums 12.01 - http://www.webwizforums.com


Topic: OPEN ACCESS links, articles, TNBC
Posted By: Lee21
Subject: OPEN ACCESS links, articles, TNBC
Date Posted: Dec 26 2011 at 10:02pm
New to TNBC? Start with these articles: reviews of the disease and treatment strategies.

FYI:
1) http://theoncologist.alphamedpress.org/content/16/suppl_1/1.lon - http://theoncologist.alphamedpress.org/content/16/suppl_1/1.lon g
Oncologist. 2011;16 Suppl 1:1-11.
Triple-negative breast cancer: an unmet medical need.
Hudis CA, Gianni L.

Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, Weill
Cornell Medical College, New York, New York, USA


2) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?report=abstract - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?report=abstract
Management Options in Triple-Negative Breast Cancer
Breast Cancer (Auckl). 2011; 5: 175–199.
Christina A. Minami,1 Debra U. Chung,2 and Helena R. Chang1,3
1David Geffen School of Medicine, The University of California at Los Angeles, Los Angeles, California, USA



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm



Replies:
Posted By: SagePatientAdvocates
Date Posted: Dec 27 2011 at 1:38am
Thanks Lee for posting these links...

http://%20theoncologist.alphamedpress.org/content/16/suppl_1/1.long%20Oncologist.%202011;16%20Suppl%201:1-11. - http:// theoncologist.alphamedpress.org/content/16/suppl_1/1.long Oncologist. 2011;16 Suppl 1:1-11.

Dr. Hudis was just named President of ASCO. He has a particular interest in TNBC and I think he is a very bright Breast Medical Oncologist.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?report=abstract - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?report=abstract

Dr. Helena Chang is a Surgical Breast Oncologist at UCLA and she, too, is very bright and interested in TNBC.

I will send you my contact info and can walk you through how to make the links “hot” so folks can open them..

by the way...have you seen..Dr. Lisa Newman?

http://surgery.med.umich.edu/general/contact/faculty/lanewman.shtml - http://surgery.med.umich.edu/general/contact/faculty/lanewman.shtml

all the best,

Steve






-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Dec 27 2011 at 8:02am
Steve,
Thanks for making the links hot; it might be helpful if you can lay out the steps to make the links hot in the posting so everyone knows how to in the future.  Otherwise, one can always copy and paste the link into the browser.
The UofM has already told the new patients that the docs operate as a team and that we should not try to get a second opinion from another doc within the system.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Dec 27 2011 at 8:22am
Dear Lee,

o.k. I will try...I agree that I would like everyone to know how to do it...it is just from past experience I think it is easier if I explain to someone when we are both in front of a computer..

Maybe you could call me in a couple of hours if my explanation doesn’t work now and I can expalin it to you and then you can tell folks..Smile

There is a little icon to the right of the W icon about the word Size above...if you click on it it says insert hyperlink...

so what I do is highlight the link I want to post..place the cursor where I want the link to appear on the post and then hit command C...then click on the hyperlink icon...then hit command V to put the link in the hyperlink (a little box will pop up on your screen called Hyperlink Properties) and then hit o.k. and the link will appear on the post “hot.”

hope it works and I hope everyone does it as needed in their posts...I always try to post a link when I am mentioning a study so that folks can read about it and not rely on my words to interpret it but rather see what the study says.

thanks again for posting..

all the best,

Steve




-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 08 2012 at 3:53pm

Collection of review articles on TNBC disease, diagnosis, treatment

Hi everyone,

I am uploading the links to some of the articles I have come across that you might find useful.  I think Judy, Donna and others have pointed to some of the articles already but I thought it might be useful to put them here as well … sometimes it has been hard to locate the threads.

At the comprehensive cancer center where I am a patient, the educational center will give hard copies of papers that a patient requests.  Because of copyright reasons, they do not give out electronic copies.

 

Triple negative breast cancer, Foulkes et al. N. Engl. J. Med. 363:1938

http://www.ncbi.nlm.nih.gov/pubmed/21067385 - (this is a good up-to-date review)

 

How I treat “triple negative” disease, Vaklavas and Forero-Torres. Curr. Treat. Options Oncol. 2011

http://www.ncbi.nlm.nih.gov/pubmed/22048876 - (one expert’s perspective)

 

Few positives for triple negative breast cancer” New item in JNCI

http://www.ncbi.nlm.nih.gov/pubmed?term=hede%20triple%20negative - (cautionary note: success in phase II trials may not translate to similar success in phase III)

 

Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer,  Kaufmann et al. Ann. Surg. Oncol. ePub 12/23/11

http://www.ncbi.nlm.nih.gov/pubmed/22193884 -

4-2-12
Breast cancer virtue issue from the Oncologist (free)
http://epub.theoncologist.com/issue/49427 - http://epub.theoncologist.com/issue/49427
Not all on TNBC, some relevant in a general way, some are basic science articles

Reviews in the Oncologist (free download or may need to subscribe to a free subscription)

http://theoncologist.alphamedpress.org/content/16/suppl_1 - http://theoncologist.alphamedpress.org/content/16/suppl_1
Many on TNBC (some you have seen here before)




-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: ds21
Date Posted: Jan 08 2012 at 4:34pm
For future reference, the link

http://www.ncbi.nlm.nih.gov/pmc/?term=triple+negative+breast+cancer - http://www.ncbi.nlm.nih.gov/pmc/?term=%22triple+negative%22+%22breast+cancer%22

will search the PubMedCentral (PMC) open access library of medical literature maintained at the National Library of Medicine for publications about TNBC.  All of the articles in this repository are freely available for anyone to download.

Dr. Lisa Carey, who helped to define TNBC as a clinical syndrome, has a recent review accessible by PMC

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919761/?tool=pmcentrez - Biology, Metastatic Patterns, and Treatment of Patients with Triple-Negative Breast Cancer
Carey K. Anders, Lisa A. Carey
Clin Breast Cancer. Author manuscript; available in PMC 2010 August 11.

David
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919761/?tool=pmcentrez -



-------------
Co-survivor


Posted By: Lee21
Date Posted: Jan 08 2012 at 4:43pm
You can access free podcasts from "The Oncologist" at

http://www.sto-online.org/ - http://www.sto-online.org/

Scroll down towards the bottom and there are several podcasts from the TNBC experts at UNC.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 08 2012 at 5:38pm
One more thing about the podcasts, if you select the IBCC4 series (drop down menu) -- you will see 2 other podcasts that are of interest; one by Hudis and one by Pegram that you may find of interest as well.

-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 09 2012 at 6:40pm
Article on estimate of tumor growth in breast cancer(open access)
http://breast-cancer-research.com/content/10/3/R41 - http://breast-cancer-research.com/content/10/3/R41


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 09 2012 at 6:52pm
A couple more that may be relevant:
(all reposted later under a single post)

Articles on the significance of tumor size and nodal status in TNBC:

 “Tumor size and survival in breast cancer--a reappraisal.”

http://www.ncbi.nlm.nih.gov/pubmed/20309006 - http://www.ncbi.nlm.nih.gov/pubmed/20309006

 "Nodal status and clinical outcomes in a large cohort of patients with triple-negative breast cancer"

http://www.ncbi.nlm.nih.gov/pubmed/21606433 - http://www.ncbi.nlm.nih.gov/pubmed/21606433

 


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 11 2012 at 11:40am

A number of restrospective studies seem to suggest that RT may be important:

 Evidence for:

1. J Clin Oncol. 2011 Jul 20;29(21):2852-8. Epub 2011 Jun 13.

 Increased risk of locoregional recurrence for women with T1-2N0 triple-negative

breast cancer treated with modified radical mastectomy without adjuvant radiation

therapy compared with breast-conserving therapy.

 Abdulkarim BS, Cuartero J, Hanson J, Desch√™nes J, Lesniak D, Sabri S.

 Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada.

bassam.abdulkarim@mcgill.ca

 Comment in

    J Clin Oncol. 2011 Jul 20;29(21):2841-3.

 

PURPOSE: To evaluate the risk of locoregional recurrence (LRR) associated with locoregional treatment of women with primary breast cancer tumors negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (triple-negative breast cancer [TNBC]). 

PATIENTS AND METHODS: Patients diagnosed with TNBC were identified from a cancer  registry in a single institution (n=768). LRR-free survival was estimated using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to  determine risk of LRR on the basis of locoregional management: breast-conserving  therapy (BCT; ie, lumpectomy and adjuvant radiation therapy [RT]) and modified radical mastectomy (MRM) in the TNBC population and T1-2N0 subgroup. 

RESULTS: At a median follow-up of 7.2 years, 77 patients (10%) with TNBC developed LRR. Five-year LRR-free survival was 94%, 85%, and 87% in the BCT, MRM, and MRM + RT groups, respectively (P < .001). In multivariate analysis, MRM (compared with BCT), lymphovascular invasion and lymph node positivity were associated with increased LRR. Conversely, adjuvant chemotherapy was associated with decreased risk of LRR. For patients with T1-2N0 tumors, 5-year LRR-free survival was 96% and 90% in the BCT and MRM groups, respectively (P = .027), and  MRM was the only independent prognostic factor associated with increased LRR compared with BCT (hazard ratio, 2.53; 95% CI, 1.12 to 5.75; P = .0264). 

CONCLUSION: Women with T1-2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT. Prospective studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC.

 PMID:  tel:21670451 - 21670451   [PubMed - indexed for MEDLINE]

 

2. Am J Clin Oncol. 2011 Jun;34(3):231-7.

 Locoregional recurrence in patients with triple-negative breast cancer:

preliminary results of a single institution study.

 Dragun AE, Pan J, Rai SN, Kruse B, Jain D.

 Department of Radiation Oncology, James Graham Brown Cancer Center, University of

Louisville, Louisville, KY 40202, USA. aedrag01@louisville.edu

 PURPOSE: To examine the impact of radiotherapy on breast cancer patients with triple-negative (ER-, PR-, HER2/neu-) disease. 

MATERIALS AND METHODS: A prospectively collected database of 152 triple negative  breast cancer patients was initiated in 2004. A total of 77 patients who had all  phases of their therapy (surgery, chemotherapy, and radiotherapy) at our institution with a minimum of 2-months follow-up are included. Patients with all  types of surgery (lumpectomy or mastectomy), chemotherapy (neoadjuvant or adjuvant), and radiotherapy (tangents only or comprehensive nodal irradiation) are included. Patients received radiotherapy in the setting of breast-conservation and in the postmastectomy setting for ‚â•5 cm primary tumors and/or ‚â•4 positive lymph nodes. Patients were divided into 2 groups for statistical analysis, based on whether they received radiotherapy or not. 

RESULTS: In the cohort, 53 (69%) received radiotherapy, 24 (31%) received no radiotherapy. The median follow-up was 23.2 months (range, 2.0-63.1). In the alive patients, the median follow-up time was 25.6 (range, 2.0-63.1) months. Patients who received radiotherapy were significantly more likely to be of a higher AJCC stage (P < 0.001) than patients who did not receive radiotherapy. Of  the patients who received radiotherapy, 33 (61.1%) did so for breast conservation. For the entire group, 1- and 3-year overall survivals are 90.9% and 86.3%, respectively. The 3-year actuarial locoregional relapse-free survival probability for patients who received radiation was higher than those who did not receive radiation (79.6% vs. 57.9%, P = 0.049). 

CONCLUSIONS: Despite significantly lower AJCC stage, patients with triple-negative breast cancer who do not undergo radiotherapy have a significantly higher risk of locoregional recurrence.

 PMID:  tel:20805742 - 20805742   [PubMed - indexed for MEDLINE]


3. Radiother. Oncol. 100(2):200-4, 2011

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial

Wang J, Shi M, Ling R, Xia Y, Luo S, Fu X, Xiao F, Li J, Long X, Wang J, Hou Z, Chen Y, Zhou B, Xu M

Department of Radiation Oncology, Fourth Military Medical University, Xi'an, China.

BACKGROUND AND PURPOSE: Triple-negative breast cancer (TNBC) presents a high risk
breast cancer that lacks the benefit from hormone treatment, chemotherapy is the
main strategy even though it exists in poor prognosis. Use of adjuvant radiation
therapy, which significantly decreases breast cancer mortality, has not been well
described among poor TNBC women. The aim of this study was to evaluate whether
the combination of chemotherapy and radiotherapy could significantly increase
survival outcomes in TNBC women after mastectomy.

PATIENTS AND METHODS: A prospective randomized controlled multi-center study was
performed between February 2001 and February 2006 and comprised 681 women with
triple-negative stage I-II breast cancer received mastectomy, of them, 315 cases
received systemic chemotherapy alone, 366 patients received radiation after the
course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS)
were estimated. Simultaneously local and systemic toxicity were observed.

RESULTS: After a median follow-up of 86.5 months, five-year RFS rates were 88.3%
and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy
alone, respectively, with significant difference between the two groups (HR 0.77
[95% CI 0.72, 0.98]; P=0.02). Five-year OS significantly improved in adjuvant
chemotherapy plus radiation group compared with chemotherapy alone (90.4% and
78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P=0.03). No severe toxicity was reported.

CONCLUSIONS: Patients received standard adjuvant chemotherapy plus radiation
therapy was more effective than chemotherapy alone in women with triple-negative
early-stage breast cancer after mastectomy.

Copyright © 2011. Published by Elsevier Ireland Ltd.

PMID: 21852010  [PubMed - indexed for MEDLINE]


2-7-12 new entry
Mammographic density and the risk of breast cancer recurrence after breast-conserving surgery
http://onlinelibrary.wiley.com/doi/10.1002/cncr.24638/abstract - http://onlinelibrary.wiley.com/doi/10.1002/cncr.24638/abstract

http://www.breastcancer.org/risk/new_research/20091109b.jsp - http://www.breastcancer.org/risk/new_research/20091109b.jsp


But not universal:

 1. Ann Surg Oncol. 2011 Oct;18(10):2858-65. Epub 2011 Mar 26.

 The negative effect of triple-negative breast cancer on outcome after

breast-conserving therapy.

 Zaky SS, Lund M, May KA, Godette KD, Beitler JJ, Holmes LR, O'Regan RM, Yu ES, Yu

DS, Landry JC.

 Department of Radiation Oncology, Emory University Winship Cancer Center,

Atlanta, GA, USA.

 

PURPOSE: To evaluate disease failure patterns and overall survival (OS) of women  with triple-negative (TN) breast cancer who underwent breast-conserving therapy (BCT) and to understand the relationship of TN tumors with other prognostic factors.

PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry identified 562 women diagnosed and/or treated with unilateral invasive breast cancer during 2003-2004 at three Emory hospitals. After medical record review, 193 eligible women, with all tumor types, received BCT. Primary endpoints (local, regional, and distant recurrences) and secondary endpoint (OS) were evaluated using chi-square tests and Cox proportional hazards models.

RESULTS: Of the 193 women, 33 (17.1%) had TN tumors and 160 (82.9%) had non-TN tumors. Patient characteristics were similar between the two tumor types; however, tumor grade and use of chemotherapy and hormones differed between the two groups. Median follow-up was 3.4 years; 22 patients had recurrence (12.2%), and 12 died (6.2%). Patients with TN tumors had higher local (12% versus 4% for non-TN) and distant recurrences (15% versus 4% for non-TN) rates (p = 0.01). On multivariate survival analyses, TN status [hazard ratio (HR) 1.8, 95% confidence  interval (CI) 1.13-2.93] and African American (AA) race (HR 1.9, 95%CI 1.2-3.07)  were independent predictors of inferior OS.

CONCLUSIONS: Patients with TN breast cancer showed significant increases in local and distant metastatic recurrence rates after BCT, and TN status and AA race were independent negative predictors of survival. For the future, identification of these high risk features may bring personalized medicine closer to reality.

 

PMID:  tel:21442346 - 21442346   [PubMed - in process]

 

Note in this paper, 30/33 of patients with TNBC had RT.


2. Crit. Rev. Oncol. Hematol. 2011, in press

Boutrus R, Taghian AG, on behalf of AROME

Radiation Oncology Department, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract  Patients with node negative and large primary tumors ≥5cm comprise a rare entity of breast cancer patients for which clear management guidelines are not available. Data about the rates of loco-regional failures (LRF) in this patient population are scarce and reporting widely varying observations. Post Mastectomy Radiation Therapy (PMRT) for this group of patients is controversial. In this review we examined the available literature discussing the LRF rates in this clinical setting and the value of adding PMRT in their management.

Quoting paper:

"In a subset analysis of 1078 patients who were enrolled in the Danish 82b&c [4] and [5] studies, Kyndi et al. [17] investigated the relationship between the biologic subtype and prognosis of patients with high-risk breast cancer (node positive and/or tumor > 5 cm and/or invasion of tumor in to skin or pectoralis fascia) treated with mastectomy with or without PMRT, sixty patients had N0 disease. Having a triple-negative or a receptor negative/Her-2 positive (Rec-/Her-2+) tumor was significantly associated with increased LRF (p = 0.01, 0.009 respectively).

Despite having the highest LRF rate, Rec-/HER-2+ tumors did not show a significant reduction of LRF after PMRT (p = 0.2). Furthermore, the reduction in the LRF rate after PMRT was significantly smaller for patients with triple negative or Rec-/Her-2+ disease when compared with Rec+/Her-2+ patients which could be explained by the increased radioresistance among patients with Rec- tumors. A conclusion could be made that patients with Rec+/HER-2- would likely benefit from PMRT, however, the higher than usual LRF rates observed among patients not receiving PMRT make these results not amenable to generalization."


Post-mastectomy RT:

http://www.ncbi.nlm.nih.gov/pubmed/21475999 - http://www.ncbi.nlm.nih.gov/pubmed/21475999

(this paper looked only at patients with mastectomy who had undergone post mastectomy RT.  Even in this group, TNBC patients had the highest loco-regional recurrence rate of 11.8% and suggested that TNBC patients may be radio-resistant).



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Martha
Date Posted: Jan 11 2012 at 1:24pm
I had the radical mastectomy, radiation and chemo as soon as I was diagnosed, and I still had recurrence - first time on the mastectomy surgery line, and the second time - nodes on my mediastinal and behind my right pectoral muscle (right breast is where my cancer started). Not to put a damper on anyone's parade.....I took all possible measures in the beginning, but still had recurrence. I'm fighting it now with the clinical trial parp inhibitor. I've had success so far - but the chemo regimen is really kicking my blood counts to the curb. I will have to stop the gemcitibine for my next treatment ( #12) due to my plts dropping so low this past week. So I will continue with only carboplatin + parp inhibitor (iniparib) for cycle 12. Then, the next scan is done after that to make sure it is still working. Last scan showed only the right pectoral node was still there. The others are gone. So that is helping me feel good about this treatment, and the fact that I still have my hair....that is also helping me feel good! Sounds silly, but I like having my hair and getting treatment that shows positive results! Good luck to you Lee.....I hope you get rid of your cancer the first time - for GOOD!

-------------
Dx 10/08;mastect 11/08; T2/N1/M0;TACX6;rads 5-6/09; recur 11/09;recur 3/10; xeloda + Ixempx5;recur 1/11; gem + carbo + iniparib 2/11; BRCA1/2 -; dx prog 1/12; Havalen Mar Apr 12;Abraxane, May-present.


Posted By: Lee21
Date Posted: Jan 11 2012 at 3:49pm
It is important to realize that many of the available studies on TNBC are retrospective in nature and relatively fewer in number due to TNBC being a recently recognized disease entity. Additionally the studies describe behavior of a population of women and in many instances other variables have not been accounted for. It is difficult to translate statistics to individuals.

TNBC is heterogeneous and defined by exclusion of only 3 markers. We need personalized medicine to tailor your (my) treatment to your (my) disease. Medical treatment for TNBC is in flux as more of what is known in the basic sciences and from clinical trials get incorporated into the standard of care. Unfortunately that could take a while.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 17 2012 at 7:53pm
Here is the link to a video you might like:
http://www.medpagetoday.com/webcast/ICHE02/ - http://www.medpagetoday.com/webcast/ICHE02/

A discussion of ASCO trial highlights by O'Shaughnessy and Haley.

The middle set of slides are on TNBC.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 17 2012 at 8:58pm
Cognitive defects associated with chemotherapy (chemo brain?)
http://www.ncbi.nlm.nih.gov/pubmed/20725909 - http://www.ncbi.nlm.nih.gov/pubmed/20725909
http://www.ncbi.nlm.nih.gov/pubmed/22184379 - http://www.ncbi.nlm.nih.gov/pubmed/22184379


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Grateful for today
Date Posted: Jan 17 2012 at 10:40pm

WIG=SCALP/HAIR CRANIAL PROSTHESIS and insurance coverage

http://www.wigindustry.com/102508c.htm - http://www.wigindustry.com/102508c.htm

(This reference was added to alphabetical list on page 4.)








Posted By: Lee21
Date Posted: Jan 18 2012 at 10:15am
Second opinions are important:
http://online.wsj.com/article/SB10001424052970203721704577159280778957336.html -
http://online.wsj.com/article/SB10001424052970203721704577159280778957336.html



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Jan 18 2012 at 10:50am
Dear Lee,

One of the most impressive things about this site is the intelligence and generosity of the participants. Many women, like yourself, on the eve of chemotherapy treatment would not be sharing the considerable knowledge they have garnered over the last month.

Yet, here you are helping our community with your informative links on various important topics. I applaud you and am genuinely moved by your efforts.

I have seen others here post encouraging/informative messages shortly before or after surgery, on the eve of chemo, during chemo, pre, during, and after radiation therapy. And of course, often, the spirit continues at other difficult times, as well. There is such a lovely spirit of helping and supporting others here. That is one of the reasons I love this forum.

I hope your treatments go well and wish you a pCR.

You have been, are and shall be in my prayers,

Steve




-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 18 2012 at 11:20am
Steve,
I am touched by your comments and the help you have given so generously to myself and everyone else on this forum.  I want to give back what I can, while I can, to the women and men using this forum. Many have already contributed so much with their time and thoughtfulness, importantly sharing their experiences and their knowledge.  I will continue to post information that I come across that I think will benefit our community.
Lee


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Wade
Date Posted: Jan 18 2012 at 11:46am
Hi Lee,

Thanks for these links, and the article on second opinions.

I signed up to an oncology website that asks doctors to evaluate pictures of slides and photos of people with various symptoms. It then gives three or four treatment and diagnosis options, and asks the doctors to vote on the options.

I was amazed to see the widely varying opinions of  the disease depicted. We were glad we had sought multiple opinions.

I hope your SLND goes well, and your nodes are clear!

Best regards,
Wade  


-------------
Wife DX 5/2011@52 2.5x3.1cm;6/2011 DD A/C 4x,Abraxane 4x; Lumpectomy, SN biopsy 10/2011; 10/27/2011 NED; Rads start 11-22-2011, Rads fin 1-11-2012; 10-2013 NED; 07-18-2014 NED; November 2018 NED


Posted By: Lee21
Date Posted: Jan 19 2012 at 5:05pm

Nutrition, supplements and physical activity

Body weight and breast cancer survival

http://www.ncbi.nlm.nih.gov/pubmed/22187127 -

stay tuned for this study:

http://www.ncbi.nlm.nih.gov/pubmed/21710192 -

 

Diet and breast cancer

http://www.ncbi.nlm.nih.gov/pubmed?term=fiber%20kampman%20belle -

http://www.ncbi.nlm.nih.gov/pubmed?term=thomson%20thompson%20pierce -

Open access

http://www.ncbi.nlm.nih.gov/pubmed/19114692 -

 

Lignans and breast cancer:

http://www.ncbi.nlm.nih.gov/pubmed/17374837 -

http://www.ncbi.nlm.nih.gov/pubmed/22113872 -

 

Soy

http://www.ncbi.nlm.nih.gov/pubmed/19221874 - open access

http://www.ncbi.nlm.nih.gov/pubmed/20980638 -

 

Green Tea

http://www.ncbi.nlm.nih.gov/pubmed?term=yuan%20butler%20tea -

 

Vitamin D

Open access:

http://www.ncbi.nlm.nih.gov/pubmed/20164683 -

http://www.ncbi.nlm.nih.gov/pubmed/22234628 -  

 

Multivitamins and other dietary supplements

http://www.ncbi.nlm.nih.gov/pubmed/21559824 -

http://www.ncbi.nlm.nih.gov/pubmed/21953120 -

 

Physical activity

http://www.ncbi.nlm.nih.gov/pubmed/21935600 -

http://www.ncbi.nlm.nih.gov/pubmed/21464032 - http://health.gov/PAGUIDELINES/guidelines/appendix1.aspx - http://health.gov/PAGUIDELINES/guidelines/appendix1.aspx

http://www.medpagetoday.com/HematologyOncology/OtherCancers/30980 - http://www.medpagetoday.com/HematologyOncology/OtherCancers/30980

 

Websites

Harvard School of Public Health Nutrition site:

http://www.hsph.harvard.edu/nutritionsource/index.html -

 

There is another site “The Cancer Project” that has downloadable pdfs on nutrition and cancer.  I am not including the link (just google it) because the organization recommends a strictly vegan diet and has been accused (surprise!) by the meat and dairy industries as a front for animal rights advocacy.  The organization is headed by physicians and the nutrition information is written by a physician and nutritionist.  Since my diagnosis I have changed my diet 180 degrees, using some of the recipes from this site.


2-23-12 entry
Curcumin
http://lpi.oregonstate.edu/infocenter/phytochemicals/curcumin/ - http://lpi.oregonstate.edu/infocenter/phytochemicals/curcumin/

3-26-12 entry
http://www.mskcc.org/cancer-care/integrative-medicine/about-herbs-botanicals-other-products - http://www.mskcc.org/cancer-care/integrative-medicine/about-herbs-botanicals-other-products
A really good website (MSKCC) to get information on supplements and alternative medicine


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 19 2012 at 5:16pm
Addendum:
1) The full article on the role of starch in breast cancer recurrence (the abstract was presented in SABCS) is still not in press.
2) Soy, a good protein source, is still controversial especially for ER+ cancers. Eating soy as whole soy found in soybeans used to make tofu, soy milk, soy yogurt is considered much better than taking soy supplements. Talk to your doctor and nutritionist first though.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 19 2012 at 5:26pm
Addendum 2
forgot to say that "The Oncologist" article on Vit D is open access if you register at the site (no cost involved).  Good summary and the most recent review on a somewhat confusing area.

Folks (gals and guys)  please feel free to add links here to website and articles you think will be of general interest.  I know that is a lot of good information embedded in this forum.  Just hard to find them sometimes... especially for a newbie.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 20 2012 at 1:37pm

More articles on the role of radiation therapy in TNBC:

 

http://www.ncbi.nlm.nih.gov/pubmed/21475999 - http://www.ncbi.nlm.nih.gov/pubmed/21475999

(this paper looked only at patients with mastectomy who had undergone post mastectomy RT.  Even in this group, TNBC patients had the highest loco-regional recurrence rate of 11.8% and suggested that TNBC patients may be radio-resistant).

Also posted under RT post.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Jan 20 2012 at 2:00pm
Dear Lee,

Thank you for posting this study.

I do not know if this study is en-pointe for our community..

The standard of care for TNBC at the moment is often lumpectomy not mastectomy except with BRCA+ women.

This study only looked at mastectomies if I read it correctly..

The only thing, for sure, in my opinion in all of this, is that treatment of TNBC can be very complex with uncertain results. At least that is my unprofessional take on things.

warmly,

Steve

http://www.ncbi.nlm.nih.gov/pubmed/21475999# - Breast Cancer Res Treat.  2011 Aug;128(3):899-906. Epub 2011 Apr 8.

Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation.

http://www.ncbi.nlm.nih.gov/pubmed?term=Panoff%20JE%5BAuthor%5D - Panoff JE ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Hurley%20J%5BAuthor%5D - Hurley J ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Takita%20C%5BAuthor%5D - Takita C ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Reis%20IM%5BAuthor%5D - Reis IM ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Zhao%20W%5BAuthor%5D - Zhao W ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Sujoy%20V%5BAuthor%5D - Sujoy V ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Gomez%20CR%5BAuthor%5D - Gomez CR ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Jorda%20M%5BAuthor%5D - Jorda M ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Koniaris%20L%5BAuthor%5D - Koniaris L ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Wright%20JL%5BAuthor%5D - Wright JL .

Source

Department of Radiation Oncology, University of Miami School of Medicine, Miami, FL 33136, USA.

Abstract

We assessed differences in locoregional outcome based on receptor status combinations in a cohort of stage II-III breast cancer patients treated with modern trimodality therapy. Medical records of 582 consecutively treated patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 were reviewed. Rate of local regional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Gray's test and by Fine and Gray's modeling approach. Median follow-up was 44.7 months. Five-year progression-free survival (PFS) was 73.9% and overall survival (OS) was 84%. The cumulative 5-year incidence of LRR as first site of failure was 6.2% (95% CI 4.2-8.7). Five-year cumulative incidence of LRR was 8.6 versus 4.4% for estrogen receptor (ER) negative versus ER positive (P = 0.017), 8.5 versus 3.4% for progesterone receptor (PR) negative versus PR positive (P = 0.011), and 1.7 versus 7.5% for HER2 positive (86% received trastuzamab) versus HER2 negative (P = 0.032). Five-year cumulative incidence of LRR was 11.8% for the triple negative subtype and 3.9% for other receptor combinations (P < 0.001). Among patients whose disease is ER positive, 5-year LRR rate was 7.8 versus 3.4% for PR negative versus PR positive (P = 0.130). The prognostic value of the triple negative and HER2 negative subtypes was maintained on multivariate analysis. In the era of HER-2 targeted therapy, tumors that are HER-2 over expressing and are treated with trastuzumab have a very low rate of LRR. ER negative, PR negative, and triple negative status are associated with increased risk of LRR.



-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 20 2012 at 2:39pm
Steve,
Thanks for bringing it up.  As you well know, there are many problems with studies on TNBC (1) very few prospective studies; (2) most retrospective with incomplete information on receptor status; (3) limited stratification in multivariate analysis. 

The quoted study is not an exception and does not specifically look at TNBC; it is not a prospective study comparing lumpectormy+RT vs mastectomy vs mastectomy+RT, which is the study we want. The closest we have to that is the Canadian study cited earlier (but still retrospective).  Panoff looks at all comers who had mastectomy with RT. The presenting stage has the following distribution: IIA (7.2%), IIB (23.1%), IIIA (39.1%), IIIB (21%), IIIC(9.4%).  I cannot find data on the % of patients with node positive disease but expect all III to have positive nodes. In this study, the TNBCs had the highest loco-regional recurrence rate. In multivariate analysis (n=580), TNBC vs all others for LRR, the HR (hazard ratio) is 3.58.

Consistent with the difference in clinical opinions offered by our care providers, the medical literature is variable as well and presently (as far as I can tell) there is no consensus.  I think there are women electing to have mastectomy not entirely based on staging recommendations.

With no validated targeted therapy available for TNBCs, we need to consider very carefully the available treatment options including RT.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 20 2012 at 3:07pm
One difference to point out between the Canadian study (Abdulkarim et al.) and Panoff's study is the stage of the patients included in the analysis.  The Canadian study looked at patients with T1-2N0 disease compared to the more advanced group in the Panoff study.

A critique of the Canadian study has been posted :
http://jco.ascopubs.org/content/29/35/4722.long - http://jco.ascopubs.org/content/29/35/4722.long



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 21 2012 at 10:25am
Reputable sites to get information for breast cancer:

http://www.cancer.gov/cancertopics/types/breast - http://www.cancer.gov/cancertopics/types/breast

(NCI)

 

http://www.cancer.org/Cancer/BreastCancer/index?ssSourceSiteId=null - http://www.cancer.org/Cancer/BreastCancer/index?ssSourceSiteId=null

(American Cancer Society)

 

http://www.cancer.net/patient/Cancer+Types - http://www.cancer.net/patient/Cancer+Types

(American Society of Clinical Oncology)

 

http://ww5.komen.org/IWasDiagnosed/IveBeenDiagnosedwithBreastCancer.html?itc=emoentpnt:5 - http://ww5.komen.org/IWasDiagnosed/IveBeenDiagnosedwithBreastCancer.html?itc=emoentpnt:5

(Susan G Komen for the cure)




-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 21 2012 at 12:08pm
Reposting the links to the first two articles in this thread:

http://theoncologist.alphamedpress.org/content/16/suppl_1/1.long - http://theoncologist.alphamedpress.org/content/16/suppl_1/1.long

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?report=abstract - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?report=abstract


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Jan 21 2012 at 12:15pm
Dear Lee,

thanks for all the links!!!! we all really appreciate your efforts.

I just emailed you the following study which is also not en-pointe because it is not specific to TNBC but it seems to argue for radiation therapy in the patients studied..

warmly,

Steve

http://www.ncbi.nlm.nih.gov/pubmed/21885207?dopt=Citation# - Int J Radiat Oncol Biol Phys.  2011 Nov 1;81(3):782-7. Epub 2011 Aug 30.

Local-regional recurrence with and without radiation therapy after neoadjuvant chemotherapy and mastectomy for clinically staged T3N0 breast cancer.

http://www.ncbi.nlm.nih.gov/pubmed?term=Nagar%20H%5BAuthor%5D - Nagar H ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Mittendorf%20EA%5BAuthor%5D - Mittendorf EA ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Strom%20EA%5BAuthor%5D - Strom EA ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Perkins%20GH%5BAuthor%5D - Perkins GH ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Oh%20JL%5BAuthor%5D - Oh JL ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Tereffe%20W%5BAuthor%5D - Tereffe W ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Woodward%20WA%5BAuthor%5D - Woodward WA ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Gonzalez-Angulo%20AM%5BAuthor%5D - Gonzalez-Angulo AM ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Hunt%20KK%5BAuthor%5D - Hunt KK ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Buchholz%20TA%5BAuthor%5D - Buchholz TA ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Yu%20TK%5BAuthor%5D - Yu TK .

Source

Department of Radiation Oncology, the University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract

PURPOSE:

The purpose of this study was to determine local-regional recurrence (LRR) risk according to whether postmastectomy radiation therapy (PMRT) was used to treat breast cancer patients with clinical T3N0 disease who received neoadjuvant chemotherapy (NAC) and mastectomy.

METHODS AND MATERIALS:

Clinicopathology data from 162 patients with clinical T3N0 breast cancer who received NAC and underwent mastectomy were retrospectively reviewed. A total of 119 patients received PMRT, and 43 patients did not. The median number of axillary lymph nodes (LNs) dissected was 15. Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test.

RESULTS:

At a median follow-up of 75 months, 15 of 162 patients developed LRR. For all patients, the 5-year LRR rate was 9% (95% confidence interval [CI], 4%-14%). The 5-year LRR rate for those who received PMRT was 4% (95% CI, 1%-9%) vs. 24% (95% CI, 10%-39%) for those who did not receive PMRT (p <0.001). A significantly higher proportion of irradiated patients had pathology involved LNs and were ≤40 years old. Among patients who had pathology involved LNs, the LRR rate was lower in those who received PMRT (p <0.001). A similar trend was observed for those who did not have pathology involved LN disease. Among nonirradiated patients, the appearance of pathologic LN disease after NAC was the only clinicopathologic factor examined that significantly correlated with the risk of LRR.

CONCLUSIONS:

Breast cancer patients with clinical T3N0 disease treated with NAC and mastectomy but without PMRT had a significant risk of LRR, even when there was no pathologic evidence of LN involvement present after NAC. PMRT was effective in reducing the LRR rate. We suggest PMRT should be considered for patients with clinical T3N0 disease.

Copyright © 2011. Published by Elsevier Inc.



-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 22 2012 at 3:31pm

Tumor size by radiographic measurements:

http://www.ncbi.nlm.nih.gov/pubmed/19886147 - http://www.ncbi.nlm.nih.gov/pubmed/19886147

correlation with surgical specimen (gold standard)

mammography          r=0.26

ultrasound                 r=0.57

MRI                             r=0.8

(r, correlation coefficient: r=0, no correlation, r=1, 100% concordance)

http://www.ncbi.nlm.nih.gov/pubmed/19800455 - http://www.ncbi.nlm.nih.gov/pubmed/19800455

MRI correlates with surgical specimen within 0.5 cm (overestimation in 33% and underestimation in 15%).  In cases where there was an overestimate, 65% of these cases had additional pathological findings in the surrounding tissue.

http://www.ncbi.nlm.nih.gov/pubmed/15325659 - http://www.ncbi.nlm.nih.gov/pubmed/15325659

an earlier study (2004)

mammography          r=0.66

ultrasound                 r=0.48

core biopsy                r=0.28

Note:  MRI is 3D, while US and Mammography are essentially 2D.  Mammography is also a problem with high breast tissue density.

Trying to determine growth of tumor using different radiographic means is probably not reliable.  For example, my tumor was 1.7cm by US on 12/8/11 and 3cm by MRI on 12/30/11. The difference is unlikely to be due to accelerated tumor growth, and more likely due to the US operator skill level (in getting the plane of the longest diameter of the tumor). 

In this paper:

http://www.ncbi.nlm.nih.gov/pubmed/20105090 - http://www.ncbi.nlm.nih.gov/pubmed/20105090

US   r=0.85

mammography r=0.71

The numbers are better but if you get the paper and look at the figures, there is  significant underestimation by US AND mammography for tumors that are greater than 2 cm.  Just so happens the patients included in this study have smaller tumors <2 cm. Mammography appears to overestimate smaller (<1 cm) tumors also.

New entry 2-4-12

http://www.ncbi.nlm.nih.gov/pubmed/21947592 - http://www.ncbi.nlm.nih.gov/pubmed/21947592

1. Ann Surg Oncol. 2011 Oct;18(11):3149-54. Epub 2011 Sep 27.

MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology
affect accuracy?

McGuire KP, Toro-Burguete J, Dang H, Young J, Soran A, Zuley M, Bhargava R,
Bonaventura M, Johnson R, Ahrendt G.

Department of Surgery, Magee-Womens Hospital, University of Pittsburgh, 300
Halket St., Pittsburgh, PA, USA. mcguirek2@mail.magee.edu

BACKGROUND: A discrepancy often exists between the post-neoadjuvant chemotherapy
(NAC) breast tumor size on magnetic resonance imaging (MRI) and pathologic tumor
size. We seek to quantify this MRI/pathology discrepancy and determine if the
accuracy of MRI post NAC varies with tumor subtype.
METHODS: The University of Pittsburgh Medical Center (UPMC) Cancer Registry and
radiology database were searched for patients with breast cancer who underwent
NAC and MRI staging between 2004 and 2009. We compared radiologic to pathologic
staging and stratified differences based on tumor biology using univariate,
multivariate, and receiver operating characteristic (ROC) analysis.
RESULTS: Two hundred three of 592 patients undergoing surgery after NAC for
breast cancer had MRI staging pre and post chemotherapy. All patients had intact
tumors prior to the initiation of chemotherapy. Average tumor size by MRI was 4.0
cm pre chemotherapy and 1.2 cm post chemotherapy. The average pathologic tumor
size was 1.7 cm (range 0-13 cm). The difference between MRI and pathologic tumor
size was greatest in luminal (1.1 cm) and least in triple-negative (TN) and human
epidermal growth factor receptor 2 (HER2)-positive tumors (<0.1 cm) (p = 0.015)
.
MRI was a good discriminator for pathologic complete response (pCR) [area under
the curve (AUC) 0.777]. Its predictive value for pCR was much greater in TN and
estrogen receptor(ER)-/HER2+ than in luminal tumors (73.6 vs. 27.3%).

CONCLUSIONS: MRI is an effective tool for predicting response to NAC. The
accuracy of MRI in estimating postchemotherapy tumor size varies with tumor
subtype. It is highest in ER-/HER2+ and TN and lowest in luminal tumors.
Knowledge of how tumor subtype affects MRI accuracy can guide recommendations for
surgery following NAC.





-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 23 2012 at 2:59pm
Staging and prognosis in TNBC:

Nodal status and clinical outcomes in a large cohort of patients with triple-negative breast cancer.

http://www.ncbi.nlm.nih.gov/pubmed/21606433%20 - -

http://www.ncbi.nlm.nih.gov/pubmed/21606433%20 -

http://www.ncbi.nlm.nih.gov/pubmed/21606433%20 - Clinical relevance of TNM staging system according to breast cancer subtypes

http://www.ncbi.nlm.nih.gov/pubmed/21242587 - Triple-negative breast cancers: unique clinical presentations and outcomes

http://www.ncbi.nlm.nih.gov/pubmed/20853062 - Tumor size and survival in breast cancer--a reappraisal

http://www.ncbi.nlm.nih.gov/pubmed?term=foulkes%20narod%20reappraisal%20 - http://www.ncbi.nlm.nih.gov/pubmed?term=foulkes%20narod%20reappraisal%20 - Time to disease recurrence in basal-type breast cancers: effects of tumor size and lymph node status

http://www.ncbi.nlm.nih.gov/pubmed/19691094 - Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status

http://www.ncbi.nlm.nih.gov/pubmed?term=foulkes%20ellis%20unreliable - http://www.ncbi.nlm.nih.gov/pubmed?term=foulkes%20ellis%20unreliable

Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer

http://www.ncbi.nlm.nih.gov/pubmed?term=crabb%20chia%20basal - Seems to me that the literature is still confusing with respect to the importance of tumor size and lymph node involvement.  Again all studies are retrospective in nature with minimal multivariate analysis.  Given that TNBC is a heterogeneous disease, it is a possibility that the distribution of TNBC patients varies between the different studies. 

All the more reason that TNBC tumors should be further distinguished based on molecular signatures.  Unless you are in a clinical trial, chances are not much is being done to understand your tumor on a molecular basis. 

If you are cured, great, but we don't know why.  If you have a recurrence, too bad, but we don't know why either.  We just don't have 10-20 years to wait around until definitive results are obtained from Phase III trials stratified according to molecular subtypes. 

2-11-12 entry

Nottingham Prognostic Index in triple-negative breast cancer: a reliable prognostic tool?

http://www.biomedcentral.com/1471-2407/11/299 - http://www.biomedcentral.com/1471-2407/11/299

In contrast to other studies, this paper says TNBC disseminate to the axillary lymph nodes as frequently as other subtypes.

3-5-12 entry

Favorable Prognosis in Patients With T1a/T1bN0 Triple-Negative Breast Cancers Treated With Multimodality Therapy

http://onlinelibrary.wiley.com/doi/10.1002/cncr.27480/abstract - http://onlinelibrary.wiley.com/doi/10.1002/cncr.27480/abstract

194 patients in retrospective study.  If you are in the lucky minority of having tumors <=1 cm, node negative, and no lymphovascular invasion this study says you'll do great.

http://www.ncbi.nlm.nih.gov/pubmed?term=crabb%20chia%20basal -



Posted By: SagePatientAdvocates
Date Posted: Jan 23 2012 at 3:11pm
Dear Lee,

again, thank you for all the links..

The first paper you mentioned above came to the conclusion that breast MRIs are more accurate in finding cancer masses than mammography or ultrasounds. 

So in this age of deteriorating health care how do many women get a Breast MR when many insurance companies give the patients a hard time getting the exam covered?

I agree with the conclusion at the bottom of your post and wondered, in the present economic environment, whether you had any suggestions to accelerate the research efforts we, as a community, so desperately need?

warmly with my thanks, again,

Steve


-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 23 2012 at 3:50pm
Very good points Steve.  I am very frustrated with what's happening in the medical field: on the one hand we have made enormous progress in understanding tumor biology at the molecular level; on the other hand, that progress has not crossed over to the clinical arena, and certainly not over to the standard of care.  The problems are fundamental as you have pointed out: escalating medical costs to the paitent that are not entirely covered by health insurance, even for the best of insurance plans (as I am finding out).  The stressed out economy doesn't help -- at all levels, including funding for basic and translational research.  The only thing I think we as citizens, cancer survivors and cancer co-survivors can do is to keep constant pressure on our representatives in state and congress (write to them and talk to your doctors -- give them an earful).  I can tell you that there is a strong sentiment that the money that has been invested in basic sciences has not paid off and that the money has been and will continue to be diverted into fields such as electronic medical records, where the goal is, as always, to find cost containment measures, not necessarily to the benefit of the patient, but might help to contain medical costs.  I personally think this is incredibly short sighted as many of the blockbuster targeted drugs have come from an understanding of the basic biology of tumor cells : Herceptin, Imatinib, Parp inhibitors .....

The ISPY-2 trial has a different design than the usual Phase1-2-3 design and may eventually be the model to test future drugs.  It is analogous to the BATTLE trial for lung cancer at MDA
http://pharmastrategyblog.com/2011/04/update-on-the-battle-trial-in-lung-cancer.html/ - http://pharmastrategyblog.com/2011/04/update-on-the-battle-trial-in-lung-cancer.html/
except that in that trial, treatment is modulated depending on outcome whereas the ISPY2 is not, for what reason I do not know.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 23 2012 at 11:36pm
Order of chemo:

http://www.ncbi.nlm.nih.gov/pubmed?term=antolin%20garcia-mata - http://www.ncbi.nlm.nih.gov/pubmed?term=antolin%20garcia-mata

Not the study referenced elsewhere.  This is a small study from Spain evaluating DD T followed by DD AC for locally advanced BC in the neoadjuvant setting.  Not TNBC and not comparing it to any other regimen.  Endpoint was toxicity.


Weekly taxol:
See the Hudis paper from the Oncologist that I posted already.
On page 5 is a graph comparing AC->T and AT-> weekly T showing a significant improvement with the latter. This is in the adjuvant setting.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 24 2012 at 9:42pm
Another review (pretty comprehensive as of 2010) on treatment options in TNBC:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882502/?tool=pubmed - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882502/?tool=pubmed

This is open access.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 25 2012 at 11:09am
Androgen receptors in TNBC:

1) Hudis review posted already has some discussion about AR

2) http://www.ncbi.nlm.nih.gov/pubmed/20164692 - http://www.ncbi.nlm.nih.gov/pubmed/20164692

Triple-negative breast cancer: role of the androgen receptor by Gucalp and Traina

3-30-12 entry

Some Triple-Negative Breast Cancers Express Androgen Receptor

By: NEIL OSTERWEIL,  Oncology Report Digital Network

03/29/12 

ORLANDO  – Triple-negative breast tumors are notorious for their ability to evade hormonal agents and targeted therapies. But a subset of these intractable tumors expresses androgen receptors, and may be vulnerable to antiandrogen drugs, investigators suggested at the symposium of the Society of Surgical Oncology.

An evaluation of cancerous and normal breast tissues from 94 patients with triple-negative breast tumors (lacking estrogen-, progesterone-, and HER2-receptor expression), showed that the androgen receptor (AR) was expressed in 23% of tumors, reported Dr. Barbara Pockaj of the Mayo Clinic in Scottsdale, Ariz., and colleagues.

AR–positive cancers occurred more frequently in older patients and were significantly associated with lymph node metastases, compared with AR-negative, triple-negative breast cancers in this small study, she said.

There was a trend toward higher tumor stage at diagnosis among patients with AR-positive tumors, but AR-positive and AR-negative patients did not differ significantly in overall or recurrence-free survival, said Dr. Pockaj.

Previous studies have suggested that 10%-43% of triple-negative breast cancers bear the androgen receptor, but the antibodies and methods used for characterizing the presence of the receptor varied significantly, making it difficult to nail down actual numbers, Dr. Pockaj said.

The investigators examined 177 tissue biopsy cores from 94 patients with triple-negative breast cancer to see whether AR-receptor expression correlated with patient and tumor factors and survival, and where expression of the receptors in different tissues from the same patients correlated with tumor progression.

The receptor was expressed in 88% of normal breast tissues in the samples, a proportion identical to that of the estrogen receptor in normal tissues from the same patients.

AR expression was detected in all 6 of 6 adjacent DCIS (ductal carcinoma in situ) samples from AR-positive patients, and in 9 of 15 DCIS samples from patients with AR-negative cancer.

All lymph node metastases from AR-positive patients were also positive, whereas no lymph node metastases from AR-negative patients were found to express the androgen receptor.

There were no significant differences between AR-positive and -negative patients in tumor grade, angiolymphatic invasion, TNM (tumor, node, metastasis) stage, or tumor size. In contrast, 16 of the 72 (22%) of the AR-negative patients had lymph node metastases, compared with 10 of 22 (46%) AR-positive patients (P = .033).

There were no significant differences in locoregional recurrences, overall survival, or disease-specific survival between positive and negative patients.

Among all 94 patients, however, the presence of lymph node metastases was associated with a significantly worse recurrence-free survival (hazard ratio, 5.502; P = .017). Chemotherapy significantly reduced that risk (HR, 0.099; P = .0004).

In multivariate analysis, the investigators found that AR expression was associated with older age (63 years vs. 57 years; P = .051) and with the presence of lymph nodes metastases (P = .033).

Although larger studies are needed, the data suggest that AR-positive, triple-negative breast cancer "has unique clinical behavior and may need different treatment," Dr. Pockaj said.

A phase II, open-label http://clinicaltrials.gov/ct2/show/NCT00468715 - trial of the antiandrogen bicalutamide (Casodex) in patients with AR-positive, estrogen- and progesterone-receptor–negative, metastatic breast cancer is currently underway in eight U.S. cancer centers.

The current study was supported by the Translational Genomics Research Institute, Phoenix, and the Mayo Clinic, Scottsdale, Ariz. Dr. Pockaj is an employee of the Mayo Clinic.


Copyright © 2012 International Medical News Group, LLC. All rights reserved.
This page was printed from www.imngoncology.com . For reprint inquires, call 877-652-5295, ext. 102.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 25 2012 at 5:54pm
Molecular subtypes of triple negative BC:

Molecular stratification of triple-negative breast cancers (open access)
http://theoncologist.alphamedpress.org/content/16/suppl_1/61.long%28open%20access%29 - http://theoncologist.alphamedpress.org/content/16/suppl_1/61.long

and associated podcast
http://theoncologistcommunity.com/breastcancer_podcasts/player.php?assets=perou/application/assets/ - http://theoncologistcommunity.com/breastcancer_podcasts/player.php?assets=perou/application/assets/

Gene expression profiling in breast cancer: classification, prognostication, and prediction (not open access)
http://www.ncbi.nlm.nih.gov/pubmed/22098854 - http://www.ncbi.nlm.nih.gov/pubmed/22098854





-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 25 2012 at 7:57pm

Definition of luminal B:

http://www.ncbi.nlm.nih.gov/pubmed/21865043 - http://www.ncbi.nlm.nih.gov/pubmed/21865043

luminal B: ER+ and/or PR+, HER2-, Ki67 >=14% or ER+ and/or PR+, HER2+

http://www.ncbi.nlm.nih.gov/pubmed/22098854 - http://www.ncbi.nlm.nih.gov/pubmed/22098854

luminal B: ER+ 90-100%, PR+ 41-53%, HER2+, 15-24%, Ki67 high, basal markers -

basal like: ER+, 0-19%, PR+, 6-13%, HER2+, 9-13%, Ki67 high, basal markers+

This paper argues for different treatment strategies in the adjuvant setting for different subtypes:

http://www.ncbi.nlm.nih.gov/pubmed/22015282 - http://www.ncbi.nlm.nih.gov/pubmed/22015282

There is a difference in local recurrence between luminal type B vs TNBC

http://www.ncbi.nlm.nih.gov/pubmed/21900114 - http://www.ncbi.nlm.nih.gov/pubmed/21900114




-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 26 2012 at 7:16pm

Timeline for Subtyping in TNBC:

Many of the cited articles are open access so you can download from the link.

Highlights

·         6 intrinsic subtypes of BC:

o   luminal A, luminal B, Her2-enriched, basal-like, normal-like, claudin-low

·       TNBC defined by IHC: the absence/low expression of ER, PR, HER2

·       Basal-like defined by gene microarray profiling (Perou, 2000, Sorliet 2001)

·       “core basal phenotype” use of IHC markers suggested:

o   http://www.ncbi.nlm.nih.gov/pubmed/15328174 - o   http://www.ncbi.nlm.nih.gov/pubmed/17650314 - o   http://www.ncbi.nlm.nih.gov/pubmed/18316557 - o   ER-, HER2-, CK5/6+ and/or EGFR+

·       70-80% of TNBCs are also basal-like and the majority of basal (but not all) are also TNBCs.

·       >75% patients with BRCA1 mutations have TNBC subtype

·       From Foulkes New Engl J Med 2010, volume 363, pg 1938:

o   TNBC, often EGFR+, often cytokeratin 5 or 17+, often cyclin E+, TP53 mutation sometimes present, often truncating

o   Basal-like, usually EGFR+, almost always CK5/17+, usually cyclin E+, TP53 mutation usually present, often truncating

o   BRCA1-related, usually EGFR+, usually CK5/17+, usually cyclin E+, TP53 mutation, nearly always present, nearly always truncating

 

Timeline of molecular subtyping :

 

Perou’s original 2000 paper (predates TNBC entity)

http://www.nature.com/nature/journal/v406/n6797/full/406747a0.html - ·            Microarray study based on 42 patients of which 36 had IDC

·     I     Identified groups ER+/luminal-like, basal-like, ErbB2 (Her2)+, normal breast

        Basal group also further characterized by IHC: cytokeratins 5/6 or 17 or both

 

Expansion of original 4 subsets to 6 (luminal A, B, C, Basal, Her2-enriched, normal), 2001

http://www.ncbi.nlm.nih.gov/pubmed/11553815 - It also should be noted that the ER+ protein category cases based on ligand binding were highly heterogeneous with respect to their gene expression profiles (18/19 were in luminal A, 5/5 in luminal B, 9/10 in luminal C, 2/7 in basal-like, 4/5 in ERBB2+, and 3/5 in normal breast-like tumors). The luminal subtype B + C tumors might represent a clinically distinct group with a different and worse disease course, in particular with respect to relapse (Fig. http://www.pnas.org.ezproxyhost.library.tmc.edu/content/98/19/10869.long#F3 - - 3 C). The potential clinical significance of this molecular subtype is highlighted by the similarities in expression of some of the genes that are characteristic of the ER-negative tumors in the basal-like and ERBB2+ subtypes (Fig. http://www.pnas.org.ezproxyhost.library.tmc.edu/content/98/19/10869.long#F1 -

 

Comparison includes BRCA1 mutation carriers, 2003

http://www.ncbi.nlm.nih.gov/pubmed/12829800 - Concludes that BRCA1 mutations are strongly associated with a basal tumor phenotype

 

Perou (2004) found that a panel of 4 antibodies to ER, HER1 (EGFR), HER2 and CK5/6 can accurately identify basal like tumors

http://www.ncbi.nlm.nih.gov/pubmed/15328174 -  

First use of Her2-enriched instead of Her2+ in gene expression subtypes

http://clincancerres.aacrjournals.org/content/14/24/8010.short - Not much discussion here about Her2-enriched – I think to include tumors that behave like Her2+ tumors that might not overexpress Her2 but may overexpress Her2 regulated genes. A small % of the TNBCs belong to the Her2-enriched subtype without overexpression of Her2.

 

Description of the claudin-low subtype, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19435916 - http://www.ncbi.nlm.nih.gov/pubmed/20813035 - http://www.ncbi.nlm.nih.gov/pubmed/20813035

 

The metaplastic tumors gene signature most closely resembles the claudin-low tumors. Metaplastic BCs are aggressive and chemo-resistant.  More stem-cell like defined by CD44+/CD24-, enriched in genes involved in epithelial-to-mesenchymal transformation (breast cells are epithelial normally and they are transformed to a more motile, more metastatic form).

 

These tumors express low levels of hormone receptors and Her2, express some basal epithelial markers but microarray analysis shows them to be distinct from the basal like tumors.

 

Other issues of interest

 

Distinguishing between luminal A and B based on Ki67, 2009

http://jnci.oxfordjournals.org/content/101/10/736.long - http://jnci.oxfordjournals.org/content/101/10/736.long

The distinction between A and B has a false positive and false negative rate of 25%

 

A recent assessment of agreement in molecular subtyping between different studies:

http://jnci.oxfordjournals.org/content/101/10/736.long - “None of the classification systems tested produced almost perfect agreement (Kappa ≥ 0.81) among observers. However, substantial interobserver agreement (70.8% to 76.1% of the samples and free-marginal Kappa scores from 0.635 to 0.701) was consistently observed in all datasets for four molecular subtypes (luminal, basal-like, HER2, and normal breast-like). When luminal cancers were subdivided (luminal A, B, and C), none of the classification systems produced substantial agreement (Kappa ≥ 0.61) in all the datasets analyzed. Analysis of each subtype separately revealed that only two (basal-like and HER2) could be reproducibly identified by independent observers (Kappa ≥ 0.81).”

 

Supervised risk predictor of breast cancer based on intrinsic subtypes, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19204204 - - http://www.ncbi.nlm.nih.gov/pubmed/19204204

 

Practical implications of gene-expression-based assays for breast oncologists

http://www.ncbi.nlm.nih.gov/pubmed/22143140 - 2-14-12 entry

Transcriptomic landscape of breast cancers through mRNA sequencing

http://www.nature.com/srep/2012/120214/srep00264/full/srep00264.html - http://www.nature.com/srep/2012/120214/srep00264/full/srep00264.html

Breast cancer is a heterogeneous disease with a poorly defined genetic landscape, which poses a major challenge in diagnosis and treatment. By massively parallel mRNA sequencing, we obtained 1.2 billion reads from 17 individual human tissues belonging to TNBC, Non-TNBC, and HER2-positive breast cancers and defined their comprehensive digital transcriptome for the first time. Surprisingly, we identified a high number of novel and unannotated transcripts, revealing the global breast cancer transcriptomic adaptations. Comparative transcriptomic analyses elucidated differentially expressed transcripts between the three breast cancer groups, identifying several new modulators of breast cancer. Our study also identified common transcriptional regulatory elements, such as highly abundant primary transcripts, including osteonectin, RACK1, calnexin, calreticulin, FTL, and B2M, and “genomic hotspots” enriched in primary transcripts between the three groups. Thus, our study opens previously unexplored niches that could enable a better understanding of the disease and the development of potential intervention strategies.

OPEN ACCESS

2-15-12 entry

Stratifying triple-negative breast cancer: which definition(s) to use?

Adamo and Anders

http://breast-cancer-research.com/content/13/2/105 - http://breast-cancer-research.com/content/13/2/105

2-16-12 entry

Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies (OPEN ACCESS)

http://www.jci.org/articles/view/45014 - http://www.jci.org/articles/view/45014

Used gene expression microarray data to classify TNBC into 6 subtypes, which only overlap to a limited extent with the intrinsic subtypes identified by Perou. The 6 subtypes identified in this study are:

Basal (BL1, BL2), immunomodulatory (IM) (which could correspond to the medullary type), mesenchymal (M), mesenchymal stem-like (MSL)(most likely the metaplastic, claudin-low), luminal androgen receptor (LAR).

Only 49% of the TNBC belong to the intrinsic basal subtype whereas 88% of the TNBC have the core basal phenotype (EGFR, cytokeratin 5/6).

Found that the LAR subtype had decreased relapse free survival compared to the other subtypes whereas the M subtype had a higher risk for distant mets.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Jan 26 2012 at 10:04pm
Dear Lee,

The amount and quality of work you have been doing for us is absolutely breathtaking, especially on the eveof your treatment program. We all wish you successful chemotherapy and our prayers are with you.

There is one important thing that I would like to add to your important summary-

You summarized “TNBC defined by IHC:the absence/low expression of ER, PR, HER2” and that is exactly the case throughout most of the country BUT Dr. Michael Press, a wonderful pathologist at USC, did a study and found that around 15% of the time IHC showed HER2neu to be negative when in fact it was positive. This is extremely important because if HER2neu+ Herceptin can be used.

The standard of care at many major cancer centers across the country is to utilize FISH tecnology in addition to IHC to measure HER2neu.

I think it is extremely important for the women in our marvelous family to ask for FISH to be done on their tumors.

http://www.medicalnewstoday.com/releases/171736.php - http://www.medicalnewstoday.com/releases/171736.php

Lee, please do not take my words as criticism in anyway...Just something that I feel, strongly, should be mentioned in your excellent overview.

again, my prayers are with you and shall be..good luck next week.

warmly,

Steve


-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 26 2012 at 11:48pm
Steve, you are absolutely correct about using FISH to test for Her2.  The current recommendation is if Her2 is 3+ and above it should be verified by FISH.

American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer
Arch Pathol Lab Med, 131:8-43, 2007

The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3 + (uniform, intense membrane staining of 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1 +, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Jan 27 2012 at 7:49am
Dear Lee,

There are several major cancer centers who use the FISH test, for all women with breast cancer, regarding HER2neu, no matter the IHC HER2 level and no matter that the guidelines are as you indicate.

I think the philosophy behind this is simple according to a pathologist who explained the rationale to me. “The implications of using Herceptin may be so important to a patient’s survival, that we just want to be as sure as possible that the HER2neu level is truly negative. FISH is back-up insurance, even in tissue samples that have been graded 3+ by IHC. We want to make sure that a mistake is not made by just relying on IHC."

all the best,

Steve




-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 27 2012 at 9:50am
Steve, I have been able to find these additional references:

Her2 testing 


How do you tell whether a breast cancer is HER2 positive? Ongoing studies keep debate in high gear

http://jnci.oxfordjournals.org/content/103/2/87.long - http://jnci.oxfordjournals.org/content/103/2/87.long


Clinical Notice for American Society of Clinical Oncology-College of American Pathologists Guideline Recommendations on ER/PgR and HER2 Testing in Breast Cancer

http://jco.ascopubs.org/content/29/15/e458.long - http://jco.ascopubs.org/content/29/15/e458.long

 

Laboratory compliance with the American Society of Clinical Oncology/college of American Pathologists guidelines for human epidermal growth factor receptor 2 testing: a College of American Pathologists survey of 757 laboratories

http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.5.728 - http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.5.728

 

Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines

http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-133.4.611 - http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-133.4.611

http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-133.4.611 -

Current NCCN guidelines:

http://www.nccn.com/about-us/61-symptoms-category.html - http://www.nccn.com/about-us/61-symptoms-category.html


On false positives and false negatives by the different methods:

Comprehensive immunohistochemical analysis of Her-2/neu oncoprotein overexpression in breast cancer: HercepTest (Dako) for manual testing and Her-2/neuTest 4B5 (Ventana) for Ventana BenchMark automatic staining system with correlation to results of fluorescence in situ hybridization (FISH)

http://www.ncbi.nlm.nih.gov/pubmed/19169706 - http://www.ncbi.nlm.nih.gov/pubmed/19169706

Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations

http://www.ncbi.nlm.nih.gov/pubmed/19204209 - http://www.ncbi.nlm.nih.gov/pubmed/19204209

HER2 gene amplification in patients with breast cancer with equivocal IHC results

http://www.ncbi.nlm.nih.gov/pubmed/21836036 - http://www.ncbi.nlm.nih.gov/pubmed/21836036

http://www.ncbi.nlm.nih.gov/pubmed/19169706 -

The last official ASCO issued guidelines was what was published in 2007.  I suspect that there are  inter-institution variations in how good their IHC and FISH assays are.


It seems to me the ASCO guidelines are mainly concerned with false positive IHC results.  I do not know the false positive and false negative thresholds nationwide.

As indicated in the first article, it is not a closed issue, certainly more will be forthcoming.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: ds21
Date Posted: Jan 27 2012 at 10:26am
Herceptin has significant side effects, notably toxicity for the heart.  This is particularly common when herceptin is used with adriamycin or other anthracyclin drugs.  The anthracyclins are first line agents for TNBC so this is a significant issue.  It is not just that you want to be sure to avoid false negatives, but also that you have a true positive before acting on it clinically.

David


-------------
Co-survivor


Posted By: SagePatientAdvocates
Date Posted: Jan 27 2012 at 11:20am
Dear Lee,

First of all, please understand I am trying to help clarify not be confrontational on this topic. My main source on this topic is Dr. Michael Press who is one of the country’s leading pathologists. I attended a presentation he made a few years ago and have had the opportunity to speak to him several times. As an aside, besides being an outstanding pathologist he is co-director of USC’s Women’s Cancer Program and in my personal opinion a caring physician and a lovely man.

http://uscnorriscancer.usc.edu/about/programleaders/press.html - http://uscnorriscancer.usc.edu/about/programleaders/press.html

The following paper, I feel, is one of the best explanations as to why FISH is important regarding HER2 testing-

http://clincancerres.aacrjournals.org/content/11/18/6598.full - http://clincancerres.aacrjournals.org/content/11/18/6598.full

from this paper-

Conclusions: Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.

This paper was written in 2005. At that time Dr. Press’s lab at USC was one of the few in the country, along with Mayo Clinic that was doing FISH. Now, it is my understanding, several more major cancer centers do FISH testing and as I mentioned in my original post several of them do it, no matter the IHC results.

As recently as a few months ago, an oncologist I know well told me he was sending the patient’s tissue out to Mike Press’s lab at USC because “I think he is the best.” 

Lee, I am not saying that any of your references are incorrect; just that there are different perspectives on this. I personally feel the major cancer centers who are doing FISH testing on all breast tumors are correct.

........

David, I agree with you entirely. It is clear that, for some women, there can be serious cardio-toxicity issues with Herceptin. At the same time, Herceptin, it seems, in many cases, helps women with HER2+ breast cancer survive. One of the key topics discussed at SABCS a few months ago was Herceptin and also the use of other experimental drugs with Herceptin in clinical trials, sometimes with superior results, at least preliminarily. 

..............................

Perhaps to better understand my views I would also like to express them on Memorial Sloan-Kettering Cancer Center’s (MSKCC) recent policy (about two years ago) of recommending that ALL women who have had surgery, at MSKCC, for ovarian cancer be recommended to meet with a Certified Genetic Counselor to discuss testing for the BRCA mutation, even absent any family history of breast/ovarian cancer. Certainly their program is not currently endorsed by the major medical bodies and can be quite expensive to administer but I know they have found women with the BRCA mutation which would not normally have been found, and that knowledge may affect the treatment these women are having, and also this knowledge is important regarding the breast cancer risk these women have, as a separate risk to ovarian cancer.

The numbers may be relatively small, to some, in the case of FISH testing and in the genetic testing at MSKCC but I believe lives are potentially being saved because of it and I still feel, as is written, “to save one life is to save mankind.” Perhaps some feel I am being overly-dramatic but I think that is what is involved in both cases. I personally don’t think that 5, 10 or 15% is an insignificant number.

warmly,

Steve




-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: ds21
Date Posted: Jan 27 2012 at 11:40am
From a purely technical perspective, the fluorescent dyes have many attractive features.  Beginning with the assumption that computers are intrinsically dumb (I know, I work with them ;), it is much easier to write. A program to automatically score fluorescently labeled slides than it is to score immunohistochemistry.  To be honest, I am surprised that FISH has not replaced IHC in most applications.  But that is only technical issue.  Really need the clinical data to make clinical decisions.

David


-------------
Co-survivor


Posted By: SagePatientAdvocates
Date Posted: Jan 27 2012 at 11:54am
http://www.breastcancer.org/symptoms/testing/types/fish.jsp - http://www.breastcancer.org/symptoms/testing/types/fish.jsp

not surprisingly, I think breastcancer.org says it much better than I. Smile

Steve


-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Jan 27 2012 at 12:08pm
Steve,

No offense taken at all.  I post these article links for a number of reasons:
1) share what I have learned with the community
2) stimulate discussion
3) promote our advocacy with our docs in areas that we may not have been paying attention to.

I think you brought up a good question regarding Her2 testing, one that affects all of us. In my case I will be asking my oncologist on Monday about retesting using FISH.
You might want to look at the first article from JNCI -- it cites Drs Press and Perez on the Her2 testing issue. As mentioned, IHC is more subjective and operator dependent -- this applies to both hormone receptor testing, Her2 testing and all other IHC based assays.

It is always good to remember that although test results come back in black and white so to speak, in reality, these are biological assays with their attendant technical considerations.

Lee


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Jan 27 2012 at 5:36pm

New molecular target in TNBC

A recent basic science study showed that PTPn12 is inactivated in some TNBCs (see Donna's post).  Consequently, multiple kinase targets are activated. The authors suggested that using a multiple kinase targeting approach with sunitinib and lapatinib would be helpful. I looked for what is known about these drugs in clinical trials. 

Conclusion:

1) these two drugs have not been used in combination in any subtype

2) most studies involving either of these drugs have not focused specifically on TNBC

3) sunitinib has not be shown to have efficacy in the settings tested

4) lapatinib is efficacious in Her2+ disease in the metastatic setting and in combination with herceptin in Her2+ early BC


Sunitinib, a multi-target tyrosine kinase inhibitor

mostly in advanced BC

Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial (2011) http://www.ncbi.nlm.nih.gov/pubmed/21569994 -

http://www.ncbi.nlm.nih.gov/pubmed/21569994 - http://www.ncbi.nlm.nih.gov/pubmed/21569994

Conclusion: sunitinib-paclitaxel was clinically inerior to bevacizumab-paclitaxel

 

Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated Her2 negative advanced breast cancer (2010)

http://www.ncbi.nlm.nih.gov/pubmed/20339913 - http://www.ncbi.nlm.nih.gov/pubmed/20339913

Conclusion: sunitinib should not be used as monotherapy for advanced Her2- BC

 

The oral tyrosine kinase inhibitors lapatinib and sunitinib: new opportunities for the treatment of brain metastases from breast cancer?

http://www.expert-reviews.com/doi/abs/10.1586/era.10.190 - http://www.expert-reviews.com/doi/abs/10.1586/era.10.190

 

No progression benefit with sunitinib in advanced breast cancer

http://www.medpagetoday.com/HematologyOncology/BreastCancer/13602 - http://www.medpagetoday.com/HematologyOncology/BreastCancer/13602

 

Previous studies targeting EGFR have used a monoclonal antibody (analogous to Herceptin) called cetuximab, which has not shown efficicay.

 

Lapatinib, kinase inhibitor of Her2 and EGFR

Lapatinib with trastuzumab for Her2 positive early breast cancer (NeoALTTO) a randomized open-label multicenter phase 3 trial (2012)

http://www.ncbi.nlm.nih.gov/pubmed/22257673 -

Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 4): a randomized phase 3 trial (2012)

http://www.ncbi.nlm.nih.gov/pubmed/22257523 -

Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial (2011)

http://www.ncbi.nlm.nih.gov/pubmed?term=lapatinib%20breast%20cancer%20trial%20triple%20negative - no benefit in TNBC


Lapatinib Fails as Breast Cancer Monotherapy

http://www.medpagetoday.com/HematologyOncology/BreastCancer/28430 - http://www.medpagetoday.com/HematologyOncology/BreastCancer/28430

(Her2 + disease)


Dual Her2 blockade better than one as neoadjuvant Tx

http://www.medpagetoday.com/HematologyOncology/BreastCancer/30699 - http://www.medpagetoday.com/HematologyOncology/BreastCancer/30699

 

Lapatinib boosts survival in breast cancer with brain mets

http://www.medpagetoday.com/MeetingCoverage/ASCO/26984 - http://www.medpagetoday.com/MeetingCoverage/ASCO/26984

(Her2+ disease, retrospective study)



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: cheeks
Date Posted: Jan 27 2012 at 6:03pm
Hi all, 

I don't really understand all that you are talking about but i know my post surgical pathology (mastectomy before chemo) report states that my tumor had the IHC analysis done and was sent for FISH analysis too. I just assumed this was a normal thing to do - my surgery was done at a local hospital connected with Moffitt - although my surgeon received a lot of his education from the University of Miami. 

Blair


-------------
Lump found 11/08
DX: 2/09 @52 TNBC
L. Mast. 3/26/09, SN-, BRCA-,
4.5 cm (post surgical)T2NOMO
Chemo: 4/09-10/09 Taxol x 12,
A/C x 4, No rad.No recon. NED 1/17. New Primary right breast TN, 2/2018.


Posted By: Lee21
Date Posted: Jan 27 2012 at 7:17pm
Blair
If your results from the two tests agree, and I assume they agree since you haven't heard anything to the contrary, then there is nothing to worry about.
It's just that there are false positives and false negatives with all the tests and one would like to be sure about the results.
Lee


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: cheeks
Date Posted: Jan 27 2012 at 8:46pm
Lee, 

Thanks for the information - i'm assuming they are both tests to confirm Her2+ or - status? Is that correct?

Thanks, 

Blair


-------------
Lump found 11/08
DX: 2/09 @52 TNBC
L. Mast. 3/26/09, SN-, BRCA-,
4.5 cm (post surgical)T2NOMO
Chemo: 4/09-10/09 Taxol x 12,
A/C x 4, No rad.No recon. NED 1/17. New Primary right breast TN, 2/2018.


Posted By: Lee21
Date Posted: Jan 28 2012 at 6:32pm
Results from two new trials on Bevacizumab (Avastin) in early stage breast cancer in the neoadjuvant setting
(first covered in thread by Donna)

German trial:
http://www.ncbi.nlm.nih.gov/pubmed/22276820 - http://www.ncbi.nlm.nih.gov/pubmed/22276820
specifically looked at TNBC pts:
663 TNBC, pCR, 27.9% no Bevacizumab, 39.3% with Beva

US trial:
http://www.ncbi.nlm.nih.gov/pubmed/22276821 - http://www.ncbi.nlm.nih.gov/pubmed/22276821
did not break out TNBC
Effect of Beva seen mainly in Hormone receptor + patients

Both studies reported increase in Grade 3/4 toxicity associated with Beva treatment

Pending study (closed)
BEATRICE:
http://clinicaltrials.gov/ct2/show/study/NCT00528567?show_locs=Y#locn - http://clinicaltrials.gov/ct2/show/study/NCT00528567?show_locs=Y#locn
looks at Beva in the adjuvant setting in TNBC

2-16-12 entry for biomarkers in Avastin

http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid%2BTumors&d_id=148&i=February+2012&i_id=815&a_id=20183 - http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid%2BTumors&d_id=148&i=February+2012&i_id=815&a_id=20183
Trials: AVADO (Her2- locally advanced/metastatic) and AVEREL (Her2+ disease locally advanced/metastatic)
Ongoing trial E5103: aim to recruit 5000 patients to test the addition of Avastin to AC->T in an adjuvant setting
Article also talks about reimbursement for Avastin


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 01 2012 at 9:17am
Radiation therapy and coronary stenosis:

1. New study from Sweden:

http://www.ncbi.nlm.nih.gov/pubmed/22203772 - http://www.ncbi.nlm.nih.gov/pubmed/22203772

J Clin Oncol. 2011 Dec 27. [Epub ahead of print]

Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer.

Nilsson G, Holmberg L, Garmo H, Duvernoy O, Sjögren I, Lagerqvist B, Blomqvist C.

Greger Nilsson, Lars Holmberg, Hans Garmo, Olov Duvernoy, Bo Lagerqvist, and Carl
Blomqvist, Uppsala University, University Hospital, Uppsala; Iwar Sjögren, Falun
Hospital, Falun, Sweden; and Lars Holmberg and Hans Garmo, King's College London,
School of Medicine, London, United Kingdom.

PURPOSE  To study distribution of coronary artery stenosis among patients with
breast cancer (BC) and to assess correlation between radiotherapy (RT) and
location of stenosis.
PATIENTS AND METHODS  A Swedish BC cohort diagnosed from 1970
to 2003 was linked to registers of coronary angiography from 1990 to 2004, which
yielded 199 patients. Stenoses of the coronary arteries were graded from 0 to 5,
where 0 indicated a normal vessel and 5 indicated occlusion. Two hotspot areas
for radiation were defined: proximal right coronary artery (prox RCA), mid and
distal left anterior descending artery and distal diagonal (mdLAD + dD). RT
regimens were categorized as high or low risk of irradiating the hotspot areas.
Left breast/chest wall was considered high risk for mdLAD + dD; left internal
mammary chain (IMC), high risk for prox RCA and mdLAD + dD from 1970 to 1995 and
thereafter solely for mdLAD + dD; and right IMC, high risk for prox RCA. Other RT
targets and no RT were considered low risk. Results were expressed in odds ratios
(ORs) and 95% CIs.
Results  For irradiated left- versus right-sided BC, the OR for
grade 3 to 5 stenosis in mdLAD + dD was 4.38 (95% CI, 1.64 to 11.7), and for
grade 4 to 5 stenosis, the OR was 7.22 (95% CI, 1.64 to 31.8). For high-risk RT
versus low-risk or no RT, the OR for grade 3 to 5 stenosis in hotspot areas was
1.90 (95% CI, 1.11 to 3.24).
CONCLUSION  An increase of stenosis in mdLAD + dD in
irradiated left-sided BC and an association between high-risk RT and stenosis in
hotspot areas for radiation indicate a direct link between radiation and location
of coronary stenoses.

PMID: 22203772  [PubMed - as supplied by publisher]

2. An older study  (open access)

http://jco.ascopubs.org/content/25/21/3031.long - http://jco.ascopubs.org/content/25/21/3031.long

3.  More studies from the UPenn/UMICH group

http://www.ncbi.nlm.nih.gov/pubmed?term=harris%20ee%20radiation%20coronary - http://www.ncbi.nlm.nih.gov/pubmed?term=%22harris%20ee%22%20radiation%20coronary

http://www.ncbi.nlm.nih.gov/pubmed?term=correa%20cr%20radiation%20coronary - http://www.ncbi.nlm.nih.gov/pubmed?term=%22correa%20cr%22%20radiation%20coronary



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Feb 01 2012 at 9:34am
< ="text/" ="" ="/B1D671CF-E532-4481-99AA-19F420D90332etdefender/huidhui.js?0=0&0=0&0=0">


1.  Dosimetric research on intensity-modulated arc radiotherapy planning for left breastcancer after breast-preservation surgery.
http://www.ncbi.nlm.nih.gov/pubmed/22284640 - http://www.ncbi.nlm.nih.gov/pubmed/22284640

2.  Rational use of intensity-modulated radiation therapy: the importance of clinical outcome.

Abstract

During the last 2 decades, intensity-modulated radiation therapy (IMRT) became a standard technique despite its drawbacks of volume delineation, planning, robustness of delivery, challenging quality assurance, and cost as compared with non-IMRT. The theoretic advantages of IMRT dose distributions are generally accepted, but the clinical advantages remain debatable because of the lack of clinical assessment of the effort that is required to overshadow the disadvantages. Rational IMRT use requires a positive advantage/drawback balance. Only 5 randomized clinical trials (RCTs), 3 in the breast and 2 in the head and neck, which compare IMRT with non-IMRT (2-dimensional technique in four fifths of the trials), have been published (as of March 2011), and all had toxicity as the primary endpoint. More than 50 clinical trials compared results of IMRT-treated patients with a non-IMRT group, mostly historical controls. RCTs systematically showed a lower toxicity in IMRT-treated patients, and the non-RCTs confirmed these findings. Toxicity reduction, counterbalancing the drawbacks of IMRT, was convincing for breast and head and neck IMRT. For other tumor sites, the arguments favoring IMRT are weaker because of the inability to control bias outside the randomized setting. For anticancer efficacy endpoints, like survival, disease-specific survival, or locoregional control, the balance between advantages and drawbacks is fraught with uncertainties because of the absence of robust clinical data.

http://www.ncbi.nlm.nih.gov/pubmed/22177877 - http://www.ncbi.nlm.nih.gov/pubmed/22177877


3.Adaptive radiation therapy for breast IMRT-simultaneously integrated boost: Three-year clinical experience.

http://www.ncbi.nlm.nih.gov/pubmed/22280808 - http://www.ncbi.nlm.nih.gov/pubmed/22280808

4.  Dosimetric comparison of three different external beam whole breast irradiation techniques.
http://www.ncbi.nlm.nih.gov/pubmed/22076811 - http://www.ncbi.nlm.nih.gov/pubmed/22076811


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Lee21
Date Posted: Feb 01 2012 at 10:08am
Thank you Donna, for posting these links.

I noticed these IMRT studies are from overseas --- do you know if IMRT is less used in the US?


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: ds21
Date Posted: Feb 01 2012 at 1:56pm
Repost - chemotherapy generations

There may be some variation in the definitions of first, second and third generation regimens from site to site, and the details matter.  For example, adriamycin/cyclophosphamide followed by a taxane is second generation, but if given on a shorter cycle with more intensive growth factor support ("Dose Dense") it is considered a third generation.  NCI has a qucik summary

http://cisnet.cancer.gov/breast/comparative.html - http://cisnet.cancer.gov/breast/comparative.html

Also a set of slides (2008) reviewing chemotherapy and the impact of newer regimens for breast cancer are available on line at

http://www.slideshare.net/fovak/advances-in-adjuvant-systemic-therapy-of-breast-cancer - http://www.slideshare.net/fovak/advances-in-adjuvant-systemic-therapy-of-breast-cancer

The slides are technical, but that is the nature of the business when you get down to the details.

David


-------------
Co-survivor


Posted By: 123Donna
Date Posted: Feb 01 2012 at 4:34pm
Lee,

Last year when I was getting several opinions regarding radiation treatment, IMRT was recommended for my situation.  I believe the machine I had was called Tomotherapy IMRT.   Because of the wide area being treated, they thought IMRT would be the best choice for me with mabye less side effects and damage?  I guess only time will tell.  I do know that it was about 2-3 times more expensive than  normal radiation.  However, I had no problem with insurance coverage.  Where I was treated in St. Louis, the cancer facility had 2 machines out of the total 4 in the whole area (two other hospitals had one machine each).  So I think because the technology is newer and the expense of the machines, not all facilities will have them.

Here are some links on IMRT:
http://www.mayoclinic.org/imrt/ - http://www.mayoclinic.org/imrt/

http:///en.wikipedia.org/wiki/Radiation_therapy#Virtual_simulation.2C_3-dimensional_conformal_radiation_therapy.2C_and_intensity-modulated_radiation_therapy - http:///en.wikipedia.org/wiki/Radiation_therapy#Virtual_simulation.2C_3-dimensional_conformal_radiation_therapy.2C_and_intensity-modulated_radiation_therapy

http://www.medicalnewstoday.com/releases/100158.php - http://www.medicalnewstoday.com/releases/100158.php

http://www.fccc.edu/cancer/types/breast/treatment/radiation/index.html - http://www.fccc.edu/cancer/types/breast/treatment/radiation/index.html

The following is from the Clinical Cancer Research of Siteman Cancer Center where I received IMRT therapy.
http://www.siteman.wustl.edu/ContentPage.aspx?id=585 - http://www.siteman.wustl.edu/ContentPage.aspx?id=585

New radiation therapy technique
Patients with head and neck cancers are benefiting from a cutting-edge radiation technique called intensity modulated radiation therapy (IMRT). K.S. Clifford Chao, M.D., and other radiologists at Siteman Cancer Center are among the few researchers nationwide who are studying the use of IMRT. As an emerging technique, IMRT precisely targets tumor cells while sparing surrounding normal tissue. This means, for example, nerves to the eyes and brain are less likely to receive unintended radiation during treatment of cancer of the nasal passages. IMRT also means the tumor gets a higher concentration of radiation than it would with conventional techniques. Chao showed that IMRT minimizes damage to salivary glands, sparing patients the long-term discomfort of dry mouth. Patients receiving conventional radiation for head and neck cancers often suffer from this side effect, which causes constant thirst and inability to speak or eat normally. Chao is assistant professor of radiology at the medical school's Department of Radiation Oncology.





-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Lee21
Date Posted: Feb 01 2012 at 8:22pm
Originally posted by 123Donna 123Donna wrote:

Michelle,

Also check out this thread:

radiation-rni_topic8602.html?KW=wbi - http://forum.tnbcfoundation.org/radiation-rni_topic8602.html?KW=wbi

Donna


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 03 2012 at 10:58am
Breast conserving surgery

Latest controversy surrounding lumpectomies:


http://www.medpagetoday.com/HematologyOncology/BreastCancer/30948 - http://www.medpagetoday.com/HematologyOncology/BreastCancer/30948

http://www.ncbi.nlm.nih.gov/pubmed/22298678 - http://www.ncbi.nlm.nih.gov/pubmed/22298678

Editorial:
http://jama.ama-assn.org/content/307/5/509.short - http://jama.ama-assn.org/content/307/5/509.short


1. JAMA. 2012 Feb 1;307(5):467-75.

Variability in reexcision following breast conservation surgery.

McCahill LE, Single RM, Aiello Bowles EJ, Feigelson HS, James TA, Barney T, Engel
JM, Onitilo AA.

Richard J. Lacks Cancer Center, Van Andel Research Institute, and Department of
Surgery, Michigan State University, Grand Rapids, MI 49503, USA.
mccahill@trinity-health.org

Comment in
    JAMA. 2012 Feb 1;307(5):509-10.

CONTEXT: Health care reform calls for increasing physician accountability and
transparency of outcomes. Partial mastectomy is the most commonly performed
procedure for invasive breast cancer and often requires reexcision. Variability
in reexcision might be reflective of the quality of care.
OBJECTIVE: To assess hospital and surgeon-specific variation in reexcision rates
following partial mastectomy.
DESIGN, SETTING, AND PATIENTS: An observational study of breast surgery performed
between 2003 and 2008 intended to evaluate variability in breast cancer surgical
care outcomes and evaluate potential quality measures of breast cancer surgery.
Women with invasive breast cancer undergoing partial mastectomy from 4
institutions were studied (1 university hospital [University of Vermont] and 3
large health plans [Kaiser Permanente Colorado, Group Health, and Marshfield
Clinic]). Data were obtained from electronic medical records and chart
abstraction of surgical, pathology, radiology, and outpatient records, including
detailed surgical margin status. Logistic regression including surgeon-level
random effects was used to identify predictors of reexcision.
MAIN OUTCOME MEASURE: Incidence of reexcision.
RESULTS: A total of 2206 women with 2220 invasive breast cancers underwent
partial mastectomy and 509 patients (22.9%; 95% CI, 21.2%-24.7%) underwent
reexcision (454 patients [89.2%; 95% CI, 86.5%-91.9%] had 1 reexcision, 48 [9.4%;
95% CI, 6.9%-12.0%] had 2 reexcisions, and 7 [1.4%; 95% CI, 0.4%-2.4%] had 3
reexcisions). Among all patients undergoing initial partial mastectomy, total
mastectomy was performed in 190 patients (8.5%; 95% CI, 7.2%-9.5%). Reexcision
rates for margin status following initial surgery were 85.9% (95% CI,
82.0%-89.8%) for initial positive margins, 47.9% (95% CI, 42.0%-53.9%) for less
than 1.0 mm margins, 20.2% (95% CI, 15.3%-25.0%) for 1.0 to 1.9 mm margins, and
6.3% (95% CI, 3.2%-9.3%) for 2.0 to 2.9 mm margins. For patients with negative
margins, reexcision rates varied widely among surgeons (range, 0%-70%; P = .003)
and institutions (range, 1.7%-20.9%; P < .001). Reexcision rates were not
associated with surgeon procedure volume after adjusting for case mix (P = .92).
CONCLUSION: Substantial surgeon and institutional variation were observed in
reexcision following partial mastectomy in women with invasive breast cancer.

PMID: 22298678  [PubMed - in process]

2-18-12 entry

Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy
http://www.ncbi.nlm.nih.gov/pubmed/21900114 - http://www.ncbi.nlm.nih.gov/pubmed/21900114
The 5-year cumulative incidence of LR was 0.8% (95% CI, 0.4% to 1.8%) for luminal A; 2.3% (95% CI, 0.8% to 5.9%) for luminal B; 1.1% (95% CI, 0.2% 7.4%) for luminal HER2; 10.8% (95% CI, 4.6% to 24.4%) for HER2; and 6.7% (95% CI, 3.6% to 12.2%) for triple negative.

2-28-12 entry

Fewer women need repeat breast cancer surgeries with new service at University of Michigan

http://www.sciencecodex.com/fewer_women_need_repeat_breast_cancer_surgeries_with_new_service_at_university_of_michigan-86867 - http://www.sciencecodex.com/fewer_women_need_repeat_breast_cancer_surgeries_with_new_service_at_university_of_michigan-86867


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 03 2012 at 4:48pm
New from Cancer journal Feb 3 2012

DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node-negative breast cancer
http://onlinelibrary.wiley.com/doi/10.1002/cncr.26352/abstract - http://onlinelibrary.wiley.com/doi/10.1002/cncr.26352/abstract
DDX1 is low in TNBC and DDX1 expression is correlated with good outcome.

The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers
http://onlinelibrary.wiley.com/doi/10.1002/cncr.26351/abstract - http://onlinelibrary.wiley.com/doi/10.1002/cncr.26351/abstract
BRCA mutation carriers were less sensitive to Taxanes than sporadic cases.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: ds21
Date Posted: Feb 03 2012 at 8:37pm
Another view of DDX1 is that it is a marker of  TNBC vs other forms of BC.  All of the TNBC markers are going to be associated with worse prognosis because TNBC itself has a worse prognosis than other BCs.  But each marker is one step closer to drugable targets and specific therapies for TNBC.

David


-------------
Co-survivor


Posted By: SagePatientAdvocates
Date Posted: Feb 03 2012 at 8:49pm
Dear Lee,

Re: latest controversies re: lumpectomies you posted above.

first of all, thank you for posting it but I have a question-

How many of the cases were TNBC? If we don’t know how many were I am not certain that this information is pertinent for our community. 

I don’t have the time to look at the data..do you know if the large number of cases were broken down as to subtypes of breast cancer or for this study all invasive breast cancer is considered one cancer?

thanks if you can illuminate.

warmly,

Steve


-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Lee21
Date Posted: Feb 03 2012 at 8:56pm
No breakdown at all into different types of BC.  It's a look at how often re-excision has to be done.  The point of the paper is to highlight the lack of an industry standard for determining when lumpectomies should be done (anywhere from 1cm to 4cm tumor size), and how much of a negative margin there should be.
Obviously these decisions have bearing on recurrence rates, irrespective of BC types.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Feb 03 2012 at 10:02pm
Dear Lee,

A friend of mine called the McCahill study to my attention. I watched this the other night.

http://www.youtube.com/watch?v=LmOqMOQDqsY - http://www.youtube.com/watch?v=LmOqMOQDqsY

I don’t mean to be a pain...My point is that I feel TNBC is a separate beast with six heads....Ideally I would like to see research done on all the TNBC subtypes but that is years away, I would imagine but in the meantime, whenever I see a study, I want to try to make sure whatever studies mentioned in this thread is pertinent to our community. Studies looking at ‘all’ breast cancer include TNBC but again I don’t know how pertinent this is for us because we are dealing with TNBC, not all breast cancer.

The bottom line question being addressed here I think are the disparities in margins across the country..This doc, from what I understand, wants to have national standards. That is a tough project, in my opinion because different surgeons seem to have different philosophies and they want their independence.

TNBC is particularly troublesome from what I understand because there is often microscopic components so it makes it difficult to know, with any certainty, whether the surgeon had clean margins. And with Invasive Ductal Carcinoma which categorizes most TNBC we have seen lots of recurrences in our TNBC family. So should there be separate guidelines for ‘margins’ for TNBC? and how can that be addressed if the McCahill cohort does not differentiate between various subtypes of breast cancer, especially, for our perspective, TNBC?

warmly,

Steve


-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: ds21
Date Posted: Feb 04 2012 at 9:27am
Agreed that the biology of TNBC is distinct from other breast cancers with primary tumor size and node status being less predictive of long term outcome in TNBC.  So there is an argument that the optimal surgical approach for TNBC might be different from other BCs, and at the very least TNBC should be split out in studies.   But where we are today, many surgeons and much of the surgical literature seems to approach all BC generically.  Still relevant to TNBC, and if we want to stay on top of surgical issues, we are going to have to look at the broader literature.

Standardization of surgical approach is an important first step.  If the surgeons cannot even agree among themselves about what constitutes "clean margins" and the necessity of re-op if there is residual tumor, how are we even going to begin to look at how TNBC should be approached vs. other tumor types?

David


-------------
Co-survivor


Posted By: Lee21
Date Posted: Feb 04 2012 at 10:45am
updated entry for tumor size by radiography

-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 05 2012 at 4:20pm
Dense breasts and the risk for BC

Clinical and epidemiological issues in mammographic density
http://www.nature.com/nrclinonc/journal/v9/n1/full/nrclinonc.2011.173.html - http://www.nature.com/nrclinonc/journal/v9/n1/full/nrclinonc.2011.173.html

Mammographic density and breast cancer risk: current understanding and future prospects
http://breast-cancer-research.com/content/13/6/223 - http://breast-cancer-research.com/content/13/6/223
(open access)

2-7-12 new entry
Mammographic density and the risk of breast cancer recurrence after breast-conserving surgery
http://onlinelibrary.wiley.com/doi/10.1002/cncr.24638/abstract - http://onlinelibrary.wiley.com/doi/10.1002/cncr.24638/abstract

http://www.breastcancer.org/risk/new_research/20091109b.jsp - http://www.breastcancer.org/risk/new_research/20091109b.jsp

Dense breasts have been a forum topic and I found these articles that may be of help.
In my own case, my 2009 mammogram said I had dense breasts and mammogram quality was poor but otherwise normal.  Neither the radiologist or the primary doc (at a major medical center) I was seeing thought to follow up with me about the risk associated with dense breasts.

I wonder how many similar situations are out there.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: SagePatientAdvocates
Date Posted: Feb 05 2012 at 4:37pm
Dear Lee and all,

thanks for this wonderful resource-I don’t have the time to look back..hopefully not a duplicate

warmly,

Steve

I think this is a very good article-

http://www.onclive.com/publications/contemporary-oncology/2010/fall-2010/Triple-Receptor-Negative-Breast-Cancer-Current-and-Future-Treatments

Triple Receptor-Negative Breast Cancer: Current and Future Treatments
Erika N. Brown, BS, MS, PharmD, and Ana M. Gonzalez-Angulo, MD
Published Online: Friday, March 4th, 2011

http://Abstract%20%20Breast%20cancer%20is%20the%20most%20frequently%20diagnosed%20malignancy%20in%20women%20in%20the%20United%20States.%20Triple%20receptor-negative%20breast%20cancer%20%28TNBC%29%20represents%20a%20small%20percentage%20of%20all%20breast%20cancers,%20but%20it%20constitutes%20the%20majority%20of%20breast%20cancers%20of%20the%20basal-like%20subtype.%20TNBC%20is%20characterized%20by%20the%20lack%20of%20expression%20of%20estrogen%20and%20progesterone%20receptors%20and%20by%20the%20lack%20of%20overexpression%20of%20human%20epidermal%20growth%20factor%20receptor-2%20%28HER2%29.%20Published%20studies%20have%20shown%20that%20TNBC%20is%20highly%20sensitive%20to%20chemotherapy%20in%20the%20neoadjuvant,%20adjuvant,%20and%20metastatic%20settings.%20Even%20with%20TNBC’s%20high%20sensitivity%20to%20chemotherapy,%20patients%20with%20TNBC%20have%20high%20recurrence%20and%20relapse%20rates.%20Many%20of%20the%20ongoing%20clinical%20trials%20available%20for%20patients%20with%20TNBC%20focus%20on%20the%20safety%20and/or%20efficacy%20of%20new,%20targeted%20agents%20given%20alone%20or%20in%20combination%20with%20standard%20or%20alternative%20chemotherapy. - http://Abstract Breast cancer is the most frequently diagnosed malignancy in women in the United States. Triple receptor-negative breast cancer (TNBC) represents a small percentage of all breast cancers, but it constitutes the majority of breast cancers of the basal-like subtype. TNBC is characterized by the lack of expression of estrogen and progesterone receptors and by the lack of overexpression of human epidermal growth factor receptor-2 (HER2). Published studies have shown that TNBC is highly sensitive to chemotherapy in the neoadjuvant, adjuvant, and metastatic settings. Even with TNBC’s high sensitivity to chemotherapy, patients with TNBC have high recurrence and relapse rates. Many of the ongoing clinical trials available for patients with TNBC focus on the safety and/or efficacy of new, targeted agents given alone or in combination with standard or alternative chemotherapy.


-------------
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates


Posted By: Grateful for today
Date Posted: Feb 06 2012 at 12:09am
BREAST CANCER

*Breast Cancer heterogeneity. One term-many entities*                         (posted 3/1/12)
http://m.jci.org/articles/view/57100" rel="nofollow - http://m.jci.org/articles/view/57100

-----------------------------------------------------------------------------

CHEMOBRAIN

*Long term effects of chemobrain. LBBC podcast*                           (posted 2/26/12
LBBC has a podcast form 5/25/11: Long term effects of chembrain uncovered.
If one goes to:    http://www.lbbc.org/" rel="nofollow - http://www.lbbc.org/
                             Put in the search box:   chemobrain   (not chemo brain)

*chemobrain info from American Cancer Society*                           (posted 2/26/12)
http://www.cancer.org/" rel="nofollow - http://www.cancer.org/        
using search: type in chemo brain.    Choose chemo brain.     (not chemobrain)

*chemo brain info from Mayo clinic site*                                           (posted 2/26/12)
http://www.mayoclinic.com/" rel="nofollow - http://www.mayoclinic.com/
using search: type in chemo brain.   Choose chemo brain.      (not chemobrain)

*chemo brain info from cancercare*                                                  (posted 2/26/12)
http://www.cancercare.org/" rel="nofollow - http://www.cancercare.org/
Click on Help by Diagnosis or topic. Under Topics: Click on chemo brain.
Click on pod cast or publication one wants.

* Some books on chemo brain*                                                         (posted 2/26/12)
Chemo brain How Cancer Therapies Can Affect Your Mind   by Ellen Clegg. 2009
Your Brain After Chemo .   by Dan Silverman, MD   Idelle Davidson. 2009


-------------------------------------------------------------------------





CHEMOTHERAPY



*Chemotherapy: Preoperative therapy.   2007 Meeting. Multiple pdf and slides by experts.*

     Presentations also on surgery/radiation/imaging research.                            (posted 3/11/12)

CTEP Meeting:     (CTEP=Cancer Therapy Evaluation Program of NCI)

“Preoperative Therapy in Invasive Breast Cancer: Reviewing the State of the Science and Exploring New Research Directions”    March 26-27, 2007

NOTE: Info from 2007.   One needs to read knowing that one will have to confirm if there is

             new info on the subjects addressed.

http://ctep.cancer.gov/highlights/20070326_meeting.htm" rel="nofollow - http://ctep.cancer.gov/highlights/20070326_meeting.htm

Info on CTEP: http://ctep.cancer.gov/default.htm" rel="nofollow - http://ctep.cancer.gov/default.htm

Maybe some one else can find more recent similar program of the CTEP on breast cancer.





*Chemotherapy: side effects, long term*

Article on Incidence of AML (acute myeloid leukemia) after breast cancer

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248346/?tool=pubmed" rel="nofollow - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248346/?tool=pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22220266" rel="nofollow - http://www.ncbi.nlm.nih.gov/pubmed/22220266              (posted 2/7/12)



*Chemotherapy: side effects: nausea and vomiting*                                    (posted 12/1/12)

"How Do I Treat a Patient with Chemotherapy-Induced Nausea and Vomiting?"

By RUDOLPH M. NAVARI, MD, PHD, FACP

Indiana University School of Medicine South Bend; Clinical Director, Harper Cancer Research Institute

Five distinct but related chemotherapy-induced nausea and vomiting syndromes: acute, delayed, anticipatory, breakthrough, and refractory.

http://journals.lww.com/oncology-times/blog/HowDoITreat/pages/post.aspx?PostID=20" rel="nofollow - http://journals.lww.com/oncology-times/blog/HowDoITreat/pages/post.aspx?PostID=20



*Chemotherapy: chemotherapy and biologics*

From U of Penn.   Stage 1 and 2 Breast Cancer.

? date of slides.

(addendum: info from ds21/David:

                           date- appears to be from October 2009 (PDF document properties)

http://www.penncancer.com/pdf/TWEED.pdf" rel="nofollow - http://www.penncancer.com/pdf/TWEED.pdf                          (posted 2/16/12)



*Chemotherapy: BCIRG-005 Trial.    AC docetaxel*

Phase III Study of Doxorubicin/cyclophosphamide with concomitant versus sequential

Docetaxel as adjuvant treatment in patients with HER2-normal, node positive breast

Cancer. BCIRG-005 Trial.   Study had every 3 week dosing. Published 2011.

http://jco.ascopubs.org/content/29/29/3877.abstract" rel="nofollow - http://jco.ascopubs.org/content/29/29/3877.abstract         (posted 2/16/12)

      

*Chemotherapy: editorial on dose dense chemo*

Meta-analysis: Should it be more than the sum of its parts?

Editorial preceeding: the following article:

Dose-Dense chemotherapy in nonmetastatic breast cancer: a systematic review and

Meta-analysis of randomized controlled trials.

http://jnci.oxfordjournals.org/content/early/2010/11/23/jnci.djq469.full.pdf" rel="nofollow - http://jnci.oxfordjournals.org/content/early/2010/11/23/jnci.djq469.full.pdf

                                                                                                                               (posted 2/16/12)



*Chemotherapy: dose dense: review and meta-analysis*

Dose-Dense chemotherapy in nonmetastatic breast cancer: a systematic review and

Meta-analysis of randomized controlled trials. 2010.

http://jnci.oxfordjournals.org/content/early/2010/11/23/jnci.djq409.full#ref-28" rel="nofollow - http://jnci.oxfordjournals.org/content/early/2010/11/23/jnci.djq409.full#ref-28

                                                                                                                                  (posted 2/16/12)

*Chemotherapy: Genetic predictors and biologic therapies*

Includes info on TAC. From SABCS2011.

Dr. Schneider. IU Simon Cancer Center    (Indianna University)                             (posted 2/16/12)

http://cme.medicine.iu.edu/iucme/conferences/sabcs2011/SCHNEIDER-SABCS.pdf" rel="nofollow - http://cme.medicine.iu.edu/iucme/conferences/sabcs2011/SCHNEIDER-SABCS.pdf



*Chemotherapy: Dose dense adjuvant chemotherapy for primary breast cancer*

2005 article by Larry Norton MD. Sloane-Kettering

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064124/" rel="nofollow - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064124/       (posted 2/12/12)



*Chemotherapy: TNBC: Adjuvant therapeutic options*

Tiffany Traina, MD   Sloane-Kettering       2011 article.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265248/?tool=pubmed" rel="nofollow - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265248/?tool=pubmed    (posted 2/16/12)



*Chemotherapy: Benefit of dose dense AC-T in ER negative, node positive breast cancer*

Authors include: Craig Henderson, MD. Edith Perez, MD, Larry Norton, MD.    2006 article.

Clifford Hudis, MD. Eric Winer, MD and others.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459540/?tool=pubmed" rel="nofollow - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459540/?tool=pubmed    (posted 2/16/12)



----------------------------------------------------------------------------------


GENE REVIEWS

Gene Reviews.
Expert-authored summaries about diagnosis, management and genetic counseling for specific inherited conditions, University of Washington.
http://www.ncbi.nlm.nih.gov/books/NBK1116/" rel="nofollow - http://www.ncbi.nlm.nih.gov/books/NBK1116/

Among some of the topics covered:
BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer
http://www.ncbi.nlm.nih.gov/books/NBK1247/" rel="nofollow - http://www.ncbi.nlm.nih.gov/books/NBK1247/
Li-Fraumeni Syndrome
http://www.ncbi.nlm.nih.gov/books/NBK1311/" rel="nofollow - http://www.ncbi.nlm.nih.gov/books/NBK1311/

-------------------------------------------------------------------------


IBC (Inflammatory Breast Cancer)

*IBC: Identifying factors that impact survival among women with inflammatory breast cancer.
Dawood S, Ueno NT, Valero V, Woodward WA, Buchholz TA, Hortobagyi GN, Gonzalez-Angulo AM, Cristofanilli M.    (2012 article)

http://www.ncbi.nlm.nih.gov/pubmed/21765048" rel="nofollow - http://www.ncbi.nlm.nih.gov/pubmed/21765048                            (posted 4/16/12)


_______________________________________________________________________________________________________



LEGAL RESOURCES



Cancer Legal Resource Center.                                                             (posted 8/6/12)

Contact the CLRC (Cancer Legal Resource Center)

      http://www.lls.edu/academics/candp/clrc.html" rel="nofollow - http://www.lls.edu/academics/candp/clrc.html

      https://www.disabilityrightslegalcenter.org/about/cancerlegalresource.cfm" rel="nofollow - https://www.disabilityrightslegalcenter.org/about/cancerlegalresource.cfm

The CLRC has a national, toll-free Telephone Assistance Line (866-THE-CLRC) where callers can receive free and confidential information about relevant laws and resources for their particular situation. Members of the CLRC's Professional Panel of attorneys, insurance agents, and accountants can provide additional assistance.    That phone number is 866-843-2572)



----------------------------------------------------------------------------------



METASTATIC BREAST CANCER



*Metastatic breast cancer: research-oligometastases treated with stereotactic body radiotherapy*

2/2012 article on research on metastatic cancer (including breast cancer regarding

treatment. Full article to be published in an upcoming print edition of the International

Jouranl of Radiation Oncology, Biology, Physics. Will need full article to tell if TNBC was

included in breast cancers in research study.

    http://news.ufl.edu/2012/02/02/tumor/" rel="nofollow - http://news.ufl.edu/2012/02/02/tumor/                (posted 2/6/12)

Addendum: from below post, thanks to Lee, here’s the link to the PubMed entry for the article:       

    http://www.ncbi.nlm.nih.gov/pubmed/22172903" rel="nofollow - http://www.ncbi.nlm.nih.gov/pubmed/22172903



*Brain metastasis.                                                                                                   (posted 11/30/12)

New Insights and Emerging Therapies for Breast Cancer Brain Metastases

By Elgene Lim, MD, PhD, Nancy U. Lin, MD | July 12, 2012    Journal Oncology.

http://www.cancernetwork.com/breast-cancer/content/article/10165/2088901?pageNumber=1" rel="nofollow - http://www.cancernetwork.com/breast-cancer/content/article/10165/2088901?pageNumber=1

http://www.cancernetwork.com/breast-cancer/content/article/10165/2088901?pageNumber=2" rel="nofollow - http://www.cancernetwork.com/breast-cancer/content/article/10165/2088901?pageNumber=2



---------------------------------------------------------------------------

PAIN                                                                                                                   



*cancer pain: 2009 audio recording of CancerCare workshop*                            (posted 2/27/12)

http://www.cancercare.org/connect_workshops/107-cancer_pain_2009-03-05" rel="nofollow - http://www.cancercare.org/connect_workshops/107-cancer_pain_2009-03-05





------------------------------------------------------------------------------


RADIOLOGY


Patient Safety: Radiation Dose in X-Ray and CT Exams                                 (posted 8/4/13)
http://www.radiologyinfo.org/en/safety/index.cfm?pg=sfty_xray" rel="nofollow - http://www.radiologyinfo.org/en/safety/index.cfm?pg=sfty_xray
My Medical Imaging History
http://www.radiologyinfo.org/en/safety/ImageWisely/7678_Medical%20Imaging%20History.pdf" rel="nofollow - http://www.radiologyinfo.org/en/safety/ImageWisely/7678_Medical%20Imaging%20History.pdf



___________________________________________________________________________________________________



RESEARCH



Thin Red Line’ Around Breast Cancer                                                                          posted 8/29/12

*UCSF Visualization Shows Why Immune System Fails to Kill Tumors in Mice

http://www.ucsf.edu/news/2012/05/11966/thin-red-line-around-breast-cancer" rel="nofollow - http://www.ucsf.edu/news/2012/05/11966/thin-red-line-around-breast-cancer



___________________________________________________________________________________________________



RESIDUAL CANCER BURDEN



*Residiual cancer burden: The MD Anderson calculator for RCB (residual cancer burden)*. (posted 3/1/12)

THE RCB calculator is used to determine risk of recurrence after breast cancer surgery that was

preceeded by neoadjuvant chemotherapy.

Find at: http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3" rel="nofollow - http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3



*Residual cancer burden: Article on RCB by W.F. Symmans and all:                                       (posted 3/1/12)

http://jco.ascopubs.org/content/25/28/4414.full" rel="nofollow - http://jco.ascopubs.org/content/25/28/4414.full



*Residual cancer burden: slides from W.F. Symmans 2007 CTEP presentation *               (posted 3/1/12)

CTEP: Cancer Therapy Evaluation Program)

http://ctep.cancer.gov/highlights/docs/symmans.pdf" rel="nofollow - http://ctep.cancer.gov/highlights/docs/symmans.pdf



--------------------------------------------------------------------------



ST.GALLEN BREAST CANCER CONFERENCE

Internatlonal Breast Cancer Conference held every 2 years in St. Gallen, Switzerland.

Here's the link with the program for the St Gallen (Switzerland) conference for 2013;

    http://www.oncoconferences.ch/dynasite.cfm?dsmid=111795" rel="nofollow - http://www.oncoconferences.ch/dynasite.cfm?dsmid=111795

A summary of the consensus from the 2011 St Gallen Breast Cancer Conference at:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100376/" rel="nofollow - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100376/

   Note: There may have been some changes in consensus since 2011.

              As usual, discuss with your physician if your plan is/was different than conference

              consensus and you have questions.



----------------------------------------------------------------------------



SURGERY



*AWS: Axillary web syndrome (cording).   Infrequent postop complication.*               (posted 2/24/12)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724805/" rel="nofollow - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724805/



-----------------------------------------------------------------------



TNBC-Triple Negative Breast Cancer



Slides from a presentation: Update on TNBC by Lisa Carey MD, UNC on TNBC.

Not sure of the date. One of her slides had a reference of 2011, so it was from 2011 or 2012.

http://whcenter.org/documents/cme/4-Carey.pdf" rel="nofollow - http://whcenter.org/documents/cme/4-Carey.pdf                                            (posted 8/2/12)



Article in "The Oncologist" 2011 on Directed Therapies on Subtypes of TNBC by Lisa Carey, MD

http://theoncologist.alphamedpress.org/content/16/suppl_1/71.full" rel="nofollow - http://theoncologist.alphamedpress.org/content/16/suppl_1/71.full           (posted 8/2/12)



International Journal on Breast Cancer.    2012.   72 articles on breast cancer.                   (posted 8/2/12)

http://www.hindawi.com/journals/ijbc/contents/" rel="nofollow - http://www.hindawi.com/journals/ijbc/contents/

Articles specific to TNBC:

-      Triple-Negative Breast Cancer: An Update on Neoadjuvant Clinical Trials

        Keith D. Amos, Barbara Adamo, and Carey K. Anders

        http://www.hindawi.com/journals/ijbc/2012/385978/" rel="nofollow - http://www.hindawi.com/journals/ijbc/2012/385978/

-      Molecular Basis of Triple Negative Breast Cancer and Implications for Therapy

        Parvin F. Peddi, Matthew J. Ellis, and Cynthia Ma

        http://www.hindawi.com/journals/ijbc/2012/217185/" rel="nofollow - http://www.hindawi.com/journals/ijbc/2012/217185/

-      Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm

        Andrew A. Davis and Virginia G. Kaklamani

        http://www.hindawi.com/journals/ijbc/2012/809291/" rel="nofollow - http://www.hindawi.com/journals/ijbc/2012/809291/

-      Advancements in the treatment of metastatic breast cancer.

        Massimo Cristofanilli, MD

        http://downloads.hindawi.com/journals/jo/2012/703858.pdf" rel="nofollow - http://downloads.hindawi.com/journals/jo/2012/703858.pdf

-      and other articles.



*Tips and tricks in triple-negative breast cancer: how to manage patients in real-life practice?

M Piccart, G Viale, P Ellis, M Abramowicz, and L Carey                                              (posted 8/30/12)

Ecancermedicalscience. 2011; 5: 217.

Published online 2011 July 19. doi: 10.3332/ecancer.2011.217

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223951/" rel="nofollow - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223951/





*Triple-negative breast cancer in focus: From biology to novel therapeutics              (posted 11/12/12)

In "Annals of Oncology" Volume 23 suppl 6 August 2012:

http://annonc.oxfordjournals.org/content/23/suppl_6.toc" rel="nofollow - http://annonc.oxfordjournals.org/content/23/suppl_6.toc

Using the above link, all articles have   free full text.

Articles are research articles and mostly European authors.

(To view specific articles titles and authors, see post on 11/12/12   12:07pm on p. 8 of this thread

   using the annonc.oxfordjournals link to access the articles.

      http://forum.tnbcfoundation.org/topic9440_post107510.html#107510" rel="nofollow - http://forum.tnbcfoundation.org/topic9440_post107510.html#107510        )



-----------------------------------------------------------------------



WIGS/SCARVES/HATS etc



*Wigs, scalp prosthesis, insurance coverage*

http://www.wigindustry.com/102508c.htm" rel="nofollow - http://www.wigindustry.com/102508c.htm









Grateful for today...............Judy











Posted By: Lee21
Date Posted: Feb 06 2012 at 8:55am
Here is the PubMed entry for Judy's paper:

http://www.ncbi.nlm.nih.gov/pubmed/22172903 - http://www.ncbi.nlm.nih.gov/pubmed/22172903

1. Int J Radiat Oncol Biol Phys. 2011 Dec 13. [Epub ahead of print]

Oligometastases Treated With Stereotactic Body Radiotherapy: Long-Term Follow-Up
of Prospective Study.

Milano MT, Katz AW, Zhang H, Okunieff P.

Department of Radiation Oncology, University of Rochester Medical Center,
Rochester, NY.

PURPOSE: To analyze the long-term survival and tumor control outcomes after
stereotactic body radiotherapy (SBRT) for metastases limited in number and
extent. METHODS AND MATERIALS: We prospectively analyzed the long-term overall
survival (OS) and cancer control outcomes of 121 patients with five or fewer
clinically detectable metastases, from any primary site, metastatic to one to
three organ sites, and treated with SBRT. Freedom from widespread distant
metastasis (FFDM) was defined as metastatic disease not amenable to local therapy
(i.e., resection or SBRT). Prognostic variables were assessed using log-rank and
Cox regression analyses. RESULTS: For breast cancer patients, the median
follow-up was 4.5 years (7.1 years for 16 of 39 patients alive at the last
follow-up visit). The 2-year OS, FFDM, and local control (LC) rate was 74%, 52%,
and 87%, respectively. The 6-year OS, FFDM, and LC rate was 47%, 36%, and 87%,
respectively. From the multivariate analyses, the variables of bone metastases (p
= .057) and one vs. more than one metastasis (p = .055) were associated with a
fourfold and threefold reduced hazard of death, respectively. None of the 17 bone
lesions from breast cancer recurred after SBRT vs. 10 of 68 lesions from other
organs that recurred (p = .095). For patients with nonbreast cancers, the median
follow-up was 1.7 years (7.3 years for 7 of 82 patients alive at the last
follow-up visit). The 2-year OS, FFDM, and LC rate was 39%, 28%, and 74%,
respectively. The 6-year OS, FFDM, and LC rate was 9%, 13%, and 65%,
respectively. For nonbreast cancers, a greater SBRT target volume was
significantly adverse for OS (p = .012) and lesion LC (p < .0001). Patients whose
metastatic lesions, before SBRT, demonstrated radiographic progression after
systemic therapy experienced significantly worse OS compared with patients with
stable or regressing disease. CONCLUSIONS: Select patients with limited
metastases treated with SBRT are long-term survivors. Future research should
address the therapeutic benefit of SBRT for these patients.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID: 22172903  [PubMed - as supplied by publisher]




-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 06 2012 at 2:49pm
Chemotherapy in TNBC

See earlier post on studies looking at Avastin in TNBC.

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer
http://www.springerlink.com/content/4x84586uvp476v01/ - http://www.springerlink.com/content/4x84586uvp476v01/
(small prospective study from Spain. Treatment: randomize to 4 cycles of doxorubicin or docetaxel followed by surgery to determine pCR and the cross-over to the other arm for chemo).

Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs.
Experimental design: Four cycles of doxorubicin (75 mg/m²) or docetaxel (100 mg/m²) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate - PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.

2-8-12 entry

Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 (open access)
http://annonc.oxfordjournals.org/content/22/8/1736.short - http://annonc.oxfordjournals.org/content/22/8/1736.short

Re-post previous listings


Triple negative breast cancer: adjuvant therapeutic options 2011
Gucalp and Traina
http://www.hindawi.com/journals/chrp/2011/696208/ - http://www.hindawi.com/journals/chrp/2011/696208/

Triple negative breast cancer: role of specific chemotherapy agents 2010
Isakoff
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882502/?tool=pubmed - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882502/?tool=pubmed

Management options in triple negative breast cancer 2011
Minami, Chung, Chang
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?tool=pubmed - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153117/?tool=pubmed

Adjuvant Capecitabine, Docetaxel, Cyclophosphamide, and Epirubicin for Early Breast Cancer: Final Analysis of the Randomized FinXX Trial
http://www.ncbi.nlm.nih.gov/pubmed/22105826 - -

http://www.ncbi.nlm.nih.gov/pubmed/22105826 - - http://www.ncbi.nlm.nih.gov/pubmed/22105826 - http://www.ncbi.nlm.nih.gov/pubmed/22105826

http://www.ncbi.nlm.nih.gov/pubmed/22105826 - -

2-11-12 entry

PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer--results at the time of surgery
http://www.ncbi.nlm.nih.gov/pubmed/21385882 - http://www.ncbi.nlm.nih.gov/pubmed/21385882
TNBC group: pCR 44.6% with the dose dense E->T->CMF and 30.4% with EC->T (but not statistically significant)

2-14-12 entry

Weekly paclitaxel in the adjuvant treatment of breast cancer (open access)
Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW, Wood WC, Davidson NE
http://www.nejm.org/doi/full/10.1056/NEJMoa0707056 - http://www.nejm.org/doi/full/10.1056/NEJMoa0707056
doses tested: 175 mg of paclitaxel/m2 x 4 every 3 weeks versus 80 mg of paclitaxel/m2 weekly x12 doses; all patients received AC x4 every 3 weeks
CONCLUSIONS: Weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with breast cancer. (ClinicalTrials.gov number, NCT00004125 [ClinicalTrials.gov].)

2-15-12 entry

Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study (2010)
http://www.ncbi.nlm.nih.gov/pubmed/20697801 - http://www.ncbi.nlm.nih.gov/pubmed/20697801
The highest pCR rate (57%) was for TNBC patients, < 40 years, grade 3 tumors.
Neoadjuvant regimen:
TAC x 2 (every 3 weeks) a) if response then proceed with 4 or 6 cycles of TAC; b) no response then randomized to either continue with TAC x 4 or to 4 cycles of vinorelbine and capecitabine) -- all every 3 week regimen.

2-16-12 entry

http://clinicaltrials.gov/ct2/show/NCT00093795?term=nct00093795&rank=1 - http://clinicaltrials.gov/ct2/show/NCT00093795?term=nct00093795&rank=1
B-38 trial closed but active, for node+ disease
compares ACT (every 3 weeks) x 6 to DD AC -> T to DD AC -> T+gemcitabine

2-17-12 entry

Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935316/?tool=pubmed - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935316/?tool=pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20519679?dopt=Abstract# - N Engl J Med.  2010 Jun 3;362(22):2053-65.

http://www.ncbi.nlm.nih.gov/pubmed?term=Swain%20SM%5BAuthor%5D - Swain SM ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Jeong%20JH%5BAuthor%5D - Jeong JH ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Geyer%20CE%20Jr%5BAuthor%5D - Geyer CE Jr ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Costantino%20JP%5BAuthor%5D - Costantino JP ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Pajon%20ER%5BAuthor%5D - Pajon ER ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Fehrenbacher%20L%5BAuthor%5D - Fehrenbacher L ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Atkins%20JN%5BAuthor%5D - Atkins JN ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Polikoff%20J%5BAuthor%5D - Polikoff J ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Vogel%20VG%5BAuthor%5D - Vogel VG ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Erban%20JK%5BAuthor%5D - Erban JK ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Rastogi%20P%5BAuthor%5D - Rastogi P ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Livingston%20RB%5BAuthor%5D - Livingston RB , http://www.ncbi.nlm.nih.gov/pubmed?term=Perez%20EA%5BAuthor%5D - Perez EA ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Mamounas%20EP%5BAuthor%5D - Mamounas EP ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Land%20SR%5BAuthor%5D - Land SR ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Ganz%20PA%5BAuthor%5D - Ganz PA ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Wolmark%20N%5BAuthor%5D - Wolmark N .


The paper by Swain et al. is noteworthy for the fact that with the original concurrent ACT dosing (A 60 mg/m2, C 600 mg/m2 and docetaxel 60 mg/m2 q3 weeks) there were 5 deaths and the protocol had to be amended to A 50 mg/m2, C 500 mg/m2 and docetaxel 75 mg/m2 q3 weeks while the sequential ACT continued with A 60 C 600 and docetaxel 100 mg/m2 q3 weeks. G-CSF was also added to the concurrent regimen (there is a 3rd arm testing A and docetaxel that also got G-CSF). The fact that they had to back down on the doses for the concurrent protocol might have contributed to the lower performance of this regimen.

The Swain paper is on the B-30 trial (National Surgical Adjuvant Breast and Bowel project NCT00003782) - the ongoing one that is closed that is closer to the DD schedule is the B-38 trial (NCT00093795).

Update 2-20-12
Patients are node-positive and have early stage operable BC. TNBC was not separated out.  Receptor stratification according to ER status only. Interestingly there was no mention of Her2 anywhere in the article.

The B-30 trial and its European counterpart
Originally posted by turtle turtle wrote:

Here's an article and link sent to me by Carey Anders, the hem/onc I saw at UNC. Until we see the results of the B38 trial, this is the best info we have for now:

http://www.medpagetoday.com/MeetingCoverage/SABCS/12193

SABCS: Mixed Results for Sequential Versus Concurrent Therapy for Breast Cancer

By Charles Bankhead, Staff Writer, MedPage Today

Published: December 16, 2008

Reviewed by  http://www.medpagetoday.com/reviewer.cfm?reviewerid=55 - Robert Jasmer, MD ; Associate Clinical Professor of Medicine, University of California, San Francisco .

SAN ANTONIO, Dec. 16 -- The debate over the superiority of sequential versus concurrent adjuvant chemotherapy for breast cancer failed to get a resolution in two large studies reported here.

Investigators in a North American trial found improved overall survival and disease-free survival with sequential therapy for patients with early-stage, node-positive breast cancer.

In contrast, a European-led study with the same types of patients and sequential and concurrent chemotherapy showed equivalent overall survival and disease-free survival.

The mixed results, reported at the San Antonio Breast Cancer Symposium, added data but no closure to an issue that has been examined in several studies on both sides of the Atlantic.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-30 trial involved 5,351 patients with node-positive breast cancer. The patients were randomized to three treatment schedules:

  • Concurrent docetaxel (Taxotere), doxorubicin (Adriamycin), and cyclophosphamide (Cytoxan) (TAC) for four cycles
  • Concurrent doxorubicin and docetaxel for four cycles (AT)
  • Doxorubicin and cyclophosphamide for four cycles, followed by four cycles of docetaxel (AC-T)

The trial was designed to answer two questions, said Sandra Swain, M.D., of Washington (D.C.) Hospital Center: Will concurrent therapy with TAC improve overall and disease-free survival versus AC-T? Is concurrent therapy with AT at least as efficacious as TAC and AC-T?

The patients had stage T1-3 on clinical examination and one or more positive lymph nodes by pathology. Patients with hormone receptor-positive tumors also received adjuvant tamoxifen.

After a median follow-up of 73 months, the AC-T had a 14% improvement in overall survival versus TAC (HR 0.86, P=0.086) and a 17% improvement versus AT (HR 0.83, P=0.034). AT demonstrated noninferiority to TAC, reflected in a TAC hazard ratio of 0.96.

Sequential AC-T demonstrated a significant advantage for disease-free survival, reflected in a 17% improvement versus TAC (HR 0.83, P=0.006) and a 20% improvement versus AT (HR 0.80, P=0.001). AT demonstrated noninferiority to TAC (HR 0.96).

Analysis of site of first recurrence showed that patients in the TAC arm had significantly more regional recurrences (35 versus 22 for AT and 16 for AC-T, P=0.02). The AT regimen was associated with significantly more distance recurrences (280 versus 257 with TAC and 218 with AC-T, P=0.009).

Subgroup analysis revealed a consistent advantage for sequential therapy, regardless of age, hormone receptor status, number of involved nodes, primary tumor size, and menopausal status.

A prespecified secondary objective of the study was to determine whether amenorrhea (≥6 months without menses) was associated with overall survival or DFS in premenopausal women.

Dr. Swain reported that amenorrheic women had a 24% improvement in overall survival (P=0.038) and a 30% improvement in DFS (P=0.00041). The association existed in all three treatment arms and was unaffected by patient age or hormone receptor status.

Grade 3-4 toxicity tended to occur more often with sequential therapy, which was associated with more vomiting, stomatitis, febrile neutropenia, and infections compared with the other two regimens.

Wolfgang Eiermann, M.D., of the Red Cross Women's Hospital in Munich, Germany, reported findings from the Breast Cancer International Research Group 005 study of adjuvant chemotherapy in 3,300 HER2-normal women.

All patients had stage T1-3, histologically-proven node-positive breast cancer. They were all 70 or younger, and all had definitive surgery and axillary lymph node dissection.

The patients were randomized to six cycles of TAC or to four cycles of AC-T. Hormone receptor-positive patients also received adjuvant tamoxifen or aromatase inhibitors for five years.

The primary endpoint was DFS, and secondary endpoints included overall survival, safety, and quality of life.

After a median follow-up of 65 months, patients randomized to TAC had a DFS of 78.9% versus 78.6% for the AC-T arm. Overall survival also was similar, 88.9% with AC-T and 88.1% with TAC. The results did not differ significantly with respect to number of positive nodes, hormone receptor status, and triple-negative receptor status.

Sequential therapy was associated with a significantly lower rates of febrile neutropenia (8.3% versus 17.9%, P<0.0001) and grade 3-4 thrombocytopenia (1.3% versus 2.5%, P=0.01).

In contrast, the AC-T regimen led to higher rates of neuropathy (42.8% versus 27.5%, P<0.0001), nail changes (44.5% versus 22.1%, P<0.0001), and myalgia (50.9% versus 35.8%, P<0.0001). The sequential regimen also was associated with higher rates of grade 3-4 arthralgia, neuropathy, fluid retention, hand-foot syndrome, and myalgia. 



Updated 2-20-12

Here's the European trial cited in the above article:
Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial
http://jco.ascopubs.org/content/29/29/3877.abstract - http://jco.ascopubs.org/content/29/29/3877.abstract
Doses tested:
TAC (75/50/500 mg/m2 q3 wks)
AC (60/600 mg/m2 q3 wks) -> Docetaxel (100 mg/m2 q3 wks)
Patients are node positive and have Her2 non amplified operable BC.
** same conclusions applied to the TNBC subset but the 5 year disease free survival is 81% in the ER+ group vs. 68.6% in the TNBC group.

2-19-12 entry
A phase II pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group.

http://www.ncbi.nlm.nih.gov/pubmed?term=Miller%20KD%5BAuthor%5D - - O'Neill A , http://www.ncbi.nlm.nih.gov/pubmed?term=Perez%20EA%5BAuthor%5D - - Seidman AD , http://www.ncbi.nlm.nih.gov/pubmed?term=Sledge%20GW%5BAuthor%5D - Preoperative Systemic Therapy in Breast Cancer (Medscape article from 2010)
http://www.medscape.org/viewarticle/717868 - http://www.medscape.org/viewarticle/717868
Pay attention to the CALGB 40603 trial for TNBC - just checked clinicaltrials.gov =>study suspended. No reasons given.
The GeparQuinto study is closed and the results were published earlier this year in NEJM

2-25-12 entry

Clinical correlates of 'BRCAness' in triple-negative breast cancer of patients receiving adjuvant chemotherapy

http://www.ncbi.nlm.nih.gov/pubmed/22357256 - http://www.ncbi.nlm.nih.gov/pubmed/22357256
Smallish study from the Netherlands, 157 TNBC patients of which 65% found to have BRCAness in their tumor profile. BRCAness defined by an assay developed by the same group.  Although patient characteristics differ between those with BRCAness vs non-BRCAness, based on this study, there is no difference in 5-year recurrence free survival.

More details:

  1. patients were treated with AC (DD or standard), FEC, TAC or CMF.
  2. Tumors that are BRCA-like had (1) BRCA1 mutations or (2) low levels of BRCA1 messenger RNA or (3) BRCA1 promoter methylation (modification of the DNA sequence that controls transcription of the gene).
  3. Patients with a T3 or T4 tumor had almost 3x the risk for relapse or metastatic disease than patients with a smaller tumor
  4. Patients with BRCA1-like tumors had significantly fewer node+ disease compared to patients with non-BRCA1 like tumor
2-29-12 entry

The pathologic complete response open question in primary therapy (2011)
http://www.ncbi.nlm.nih.gov/pubmed/22043049 - http://www.ncbi.nlm.nih.gov/pubmed/22043049
good article but not OPEN ACCESS

3-1-12 entry

GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer
http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2012.02231.x/abstract - http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2012.02231.x/abstract

3-2-12 entry
Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs
http://www.ncbi.nlm.nih.gov/pubmed/22264790 - http://www.ncbi.nlm.nih.gov/pubmed/22264790
Study in lung cancer but makes the point of the importance of dose scheduling

3-7-12 note
I've added a new post on Taxanes, too long to append here.

3-14-12 entry

Cancer immunotherapy--revisited
http://www.ncbi.nlm.nih.gov/pubmed/21804596 - http://www.ncbi.nlm.nih.gov/pubmed/21804596
Reason for this entry is the discussion that chemo agents (A, C, T, F, M, platinum) have effects in addition to direct killing of tumor cells.  Specifically, effects on the immune system that assist in tumor killing.  These are not findings that are readily apparent in in vitro cell line assays, which do not take into account the tumor microenvironment where a lot is happening (interactions between tumor cells and immune cells, vascular endothelium....)

Mitosis is not a key target of microtubule agents in patient tumors

http://www.nature.com/nrclinonc/journal/v8/n4/abs/nrclinonc.2010.228.html - http://www.nature.com/nrclinonc/journal/v8/n4/abs/nrclinonc.2010.228.html
An article that looks at why microtubule targeting agents (e.g. taxanes and epothilones) are effective and why mitosis-specific drugs are not.  MTAs are effective because they target not only dividing cells but also non dividing cells by interfering with the microtubule structures and affecting cellular processes such as intracellular trafficking.

3-18-12 entry

Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer
http://www.springerlink.com/content/l88k6453022t1528/ - http://www.springerlink.com/content/l88k6453022t1528/
(not open access but would recommend that you get the entire article if you are on/had neoadjuvant treatment)

3-26-12 entry
Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 (open access)
http://annonc.oxfordjournals.org/content/22/8/1736.full - http://annonc.oxfordjournals.org/content/22/8/1736.full
recommend that you take a look - current thinking

3-31-12 entry
Dissecting the Heterogeneity of Triple-Negative Breast Cancer (not open access)
http://jco.ascopubs.org/content/early/2012/03/21/JCO.2011.38.2010.abstract - http://jco.ascopubs.org/content/early/2012/03/21/JCO.2011.38.2010.abstract
Highlights from the paper:
  • While 80-90% of BRCA1-associated tumors are TNBC, no such association is present for BRCA2
  • MA.5 phase 3 trial: superiority of CMF over CEF in a subset of patients with basal phenotype (small patient size --> not statistically significant)
  • meta analysis of 5 trials suggests that  anthracycline-containing regimens more active than CMF in the TNBC subgroup
  • Rocca et al.  JCO 29:87s, 2011 abstract -  E+CMF is more active than CMF (randomized phase) in terms of 5 year disease free survival and overall survival
  • Lack of convincing evidence supporting a role for EGFR as a driver of BC oncogenesis
  • striking pCR rates for BRCA1 associated tumors with single agent cisplatin; role for platinums in non BRCA mutated tumors still not clear
  • good review of current status of PARPi (if you are interested in PARPi, consider obtaining the article from your cancer center): onl veliparib and olaparib are able to inhibit PARP1/2. Iniparib was able to suppress genes involved in telomere function.
  • although the rationale for the use of PARPi is clear in the cases of BRCA associated tumors, there could still be a benefit for PARPi in non-BRCA associated tumors because many chemo agents cause DNA damage that PARP is needed for repair, hence inhibiting PARPs could act to sensitize chemo agents
  • BiPar phase 3 study -- although the trial did not meet pre-specificed stats, there is a signal for the Gem/Cisplatin/Iniparib arm, what is not clear is where the signal is coming from.
Two trials relevant to TNBC

Paclitaxel With or Without Carboplatin and/or Bevacizumab Followed By Doxorubicin and Cyclophosphamide in Treating Patients With Breast Cancer That Can Be Removed by Surgery

http://clinicaltrials.gov/ct2/show/NCT00861705?term=NCT00861705&rank=1 - http://clinicaltrials.gov/ct2/show/NCT00861705?term=NCT00861705&rank=1
Active, 373 sites -- sounds like a whopper of a regimen (T +/- carboplatin or Avastin + DD AC )

Triple Negative Breast Cancer Trial (TNT)
http://clinicaltrials.gov/ct2/show/NCT00532727?term=NCT00532727&rank=1 - http://clinicaltrials.gov/ct2/show/NCT00532727?term=NCT00532727&rank=1
UK only




-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 06 2012 at 10:27pm
Imaging in breast cancer

There has been a lot of discussion on this forum about the value of different imaging modalities in breast cancer, including metastatic staging at the time of diagnosis. I found this review (open access) that discusses the pros and cons of radiotracer imaging techniques, including SNLBs. One thing I thought interesting is that unless peri-lesional injections (i.e. injections around the tumor) of the tracer/dye are done, depending on tumor location, internal mammary nodes may not be picked up.  Even if there is no plan to go after the IM nodes, the review thought it still useful to know the drainage pattern of the tumor because it may have prognostic value.

I will add others to this post as I find more.

The role of radiotracer imaging in the diagnosis and management of patients with breast cancer: part 1--overview, detection, and staging
http://jnm.snmjournals.org/content/50/4/569.short - http://jnm.snmjournals.org/content/50/4/569.short

2-10-12 entry
Lymphatic drainage patterns from the breast
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356216/?tool=pubmed - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356216/?tool=pubmed
open access
(peri-lesional injection of tracer: a look at lymphatic drainage pattern according to location of breast tumor and may explain why mets to internal mammary chain occur even in the face of a negative axilla)

Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan
http://www.redjournal.org/article/S0360-3016%2804%2900655-8/abstract - http://www.redjournal.org/article/S0360-3016%2804%2900655-8/abstract
(
peri-lesional injection of tracer: 14% of all patients found to have drainage to IM nodes with mets.  Incidence ranges from a low of 4% in axillary node-negative tumors with tumor in the upper outer quadrant to a high of 72% in axillary node-positive tumors with tumor in the lower medial quadrant)

3-1-12 entry
New imaging modality in BC - breast tomosynthesis
http://www.ncbi.nlm.nih.gov/pubmed?term=breast%20tomosynthesis - http://www.ncbi.nlm.nih.gov/pubmed?term=%22breast%20tomosynthesis%22
Caveat: one article says this new modality may significantly underestimate breast density, a risk factor for breast cancer



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Grateful for today
Date Posted: Feb 07 2012 at 7:43pm
Added: Article on Incidence of AML (acute myeloid leukemia) after breast cancer
to prior above post of 2/6/12 12:09      
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248346/?tool=pubmed - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248346/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/22220266 - http://www.ncbi.nlm.nih.gov/pubmed/22220266
        Judy


Posted By: turtle
Date Posted: Feb 08 2012 at 10:14am
Lee,

I'd also like to weigh in on this issue with my own spin. As someone who actually (ironically) does basic science research on vascular development in the context of normal and pathological angiogenesis (such as occurs in tumors), when I saw the large blood vessel light up on my diagnostic ultrasound even before my tumor biopsy, I knew things weren't looking good. I asked my oncologist if they would be doing CD31 (PECAM, blood vessel marker) IHC on my tumor sections and she said it wasn't performed, and wouldn't in any case change the course of treatment. However, given that TNBC is thought to disseminate through the vasculature as well as lymphatics, I wonder if this analysis would be a useful prognostic indicator of metastasis (see articles referenced below). I do agree with her however, in that ultimately, what we really want to know is how to kill those cells that have escaped the original tumor. Right now, we can only determine that empirically, which is not very satisfying from a scientific standpoint or from the veiw of the patient.

http://www.ncbi.nlm.nih.gov/pubmed/22180017# - Cancer.  2011 Dec 16. doi: 10.1002/cncr.26711. [Epub ahead of print]

The prognostic significance of lymphovascular invasion in invasive breast carcinoma.

http://www.ncbi.nlm.nih.gov/pubmed?term=Rakha%20EA%5BAuthor%5D -

Source

Department of Histopathology, Nottingham University Hospitals National Health Service Trust, Nottingham, United Kingdom. emadrakha@yahoo.com


http://www.ncbi.nlm.nih.gov/pubmed/22180017 - http://www.ncbi.nlm.nih.gov/pubmed/22180017


http://www.ncbi.nlm.nih.gov/pubmed?term=lymphangiogenesis%20and%20TNBC# - Int J Surg Pathol.  2009 Dec;17(6):426-31. Epub 2009 Jun 3.

Lymphangiogenic characteristics of triple negativity in node-negative breast cancer.

http://www.ncbi.nlm.nih.gov/pubmed?term=Liu%20HT%5BAuthor%5D - Liu HT ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Ma%20R%5BAuthor%5D - Ma R ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Yang%20QF%5BAuthor%5D - Yang QF ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Du%20G%5BAuthor%5D - Du G ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Zhang%20CJ%5BAuthor%5D - Zhang CJ .

Source

Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, China. htliu09@163.com


http://www.ncbi.nlm.nih.gov/pubmed?term=lymphangiogenesis%20and%20TNBC - http://www.ncbi.nlm.nih.gov/pubmed?term=lymphangiogenesis%20and%20TNBC


And here is a good review which addresses the VEGF inhibitor Avastin:


http://www.ncbi.nlm.nih.gov/pubmed/21779425# - Genes Cancer.  2010 Jan;1(1):12-25.

Mechanisms of resistance to anti-angiogenic therapy and development of third-generation anti-angiogenic drug candidates.

http://www.ncbi.nlm.nih.gov/pubmed?term=Loges%20S%5BAuthor%5D - Loges S ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Schmidt%20T%5BAuthor%5D - Schmidt T ,  http://www.ncbi.nlm.nih.gov/pubmed?term=Carmeliet%20P%5BAuthor%5D -

Source

Vesalius Research Center (VRC), Leuven, Belgium.


http://www.ncbi.nlm.nih.gov/pubmed/21779425 - http://www.ncbi.nlm.nih.gov/pubmed/21779425



-------------
DX IDC TNBC 1/15/12 @ 46; MRI 2.4cm gr3 BRCA2+ 6174delT; LMX 1/31/12 2.5cm, pT2pNO(i)pMX, lymphovascular invasion present; 2/20/12 TAC X 6; 7/2/12 Rad X 25; 9/27/2012 2nd mastectomy & BSO surgery


Posted By: cheeks
Date Posted: Feb 08 2012 at 10:42am
Lee, 

Is this the type of stuff i was injected with a little while before they took me to surgery for my mastectomy? I was a little doped up and don't remember clearly what they told me. 

Blair


-------------
Lump found 11/08
DX: 2/09 @52 TNBC
L. Mast. 3/26/09, SN-, BRCA-,
4.5 cm (post surgical)T2NOMO
Chemo: 4/09-10/09 Taxol x 12,
A/C x 4, No rad.No recon. NED 1/17. New Primary right breast TN, 2/2018.


Posted By: Lee21
Date Posted: Feb 08 2012 at 10:43am
Turtle, I welcome you to post on the OPEN ACCESS thread.  Neovascularization is a critical turning point in a tumor's path to increasing malignancy and metastatic potential, along with epithelial-to-mesenchymal transition (EMT) - both features are prominent in subtypes of TNBC.  I had posted a timeline of molecular subtyping of TNBC earlier here that may be of interest to you. Charles Perou in your neck of the woods is the leading authority of molecular subtypes in TNBC.

On the doppler portion of my ultrasound, they noted "mild internal vascularity" and I wondered about neovascularization as well.

As I have discovered since starting down this path 2 months ago, there is a huge gap between what is known in the laboratory and what is the standard of care in clinical practice.  Even if one knows everything that is to know in mice (not that we do) making that knowledge transferrable to humans is a tall order.  Lots of good basic science groups are doing research in TNBC (the last frontier so to speak in BC) so I am hopeful that something groundbreaking (i.e. targeted therapy) will happen soon.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 08 2012 at 2:18pm

Proposed new staging system (2009,2011)

Novel staging system for predicting disease-specific survival in patients with breast cancer treated with surgery as the first intervention: time to modify the current American Joint Committee on Cancer staging system http://www.ncbi.nlm.nih.gov/pubmed/22084362 -

http://www.ncbi.nlm.nih.gov/pubmed/22084362 - http://www.ncbi.nlm.nih.gov/pubmed/22084362

TNBC is broken out as are a number of known prognostic factors: lymphovascular invasion and tumor grade.  

Results based on a retrospective study from 1997 to 2006 at MDA and include patients who had surgery as the first intervention.  Caveat on outcome: dates of inclusion largely predate the use of Herceptin for HER2+ disease.

Related articles:

Breast cancer prognostic classification in the molecular era: the role of histological grade

http://breast-cancer-research.com/content/12/4/207 - http://breast-cancer-research.com/content/12/4/207

Triple negative breast cancer: Proposals for a pragmatic definition and implications for patient management and trial design

http://www.thebreastonline.com/article/S0960-9776%2811%2900330-4/abstract - http://www.thebreastonline.com/article/S0960-9776%2811%2900330-4/abstract


http://www.ncbi.nlm.nih.gov/pubmed/22084362 -



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Charlene
Date Posted: Feb 08 2012 at 3:07pm

Lee,

Very interesting.  I remember that the Adjuvant Online stats that my oncologist showed me did include ER status, grade and lymph node status.  Nothing about EGFR--I'm not sure that that is a standard test yet.  But, at least there's progress, right?
Thanks,
Charlene


-------------
DX 3/10 @59 ILC/TNBC
Stage 1, Grade 2, Multifocal; Lumpectomy/re-excision
SNB 0/4 nodes, BRCA-; Taxotere/Cytoxan X4, 30 rads
3/14:NED


Posted By: Lee21
Date Posted: Feb 08 2012 at 4:11pm
Charlene, I apologize -- see correction above.  I was in a hurry and didn't see the "2" wrapped around in the next row. Sorry to disappoint.  Epidermal growth factor receptor (EGFR) is one of the core basal markers but since this is a retrospective study predating many things, including the importance of molecular subtypes in TNBC.

-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 08 2012 at 6:09pm
Note to everyone who checks the OPEN ACCESS listings:
Probably figured out what I am trying to do.  Rather than have a new post every time I see something of interest, I will update a previous post on the same topic.  I will include a date to signify the new entry. Otherwise it will get too big very quickly.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 08 2012 at 6:17pm
Metastatic TNBC and metastasis

Metastatic behavior of breast cancer subtypes (open access)

http://jco.ascopubs.org/content/28/20/3271.full - http://jco.ascopubs.org/content/28/20/3271.full

Disseminated tumor cells in biologic subtypes of stage I-III breast cancer patients (open access)
http://www.springerlink.com/content/r5262346j0n40m01/ - http://www.springerlink.com/content/r5262346j0n40m01/
(open access article, good news for TNBC?  After pCR, disseminated tumor cells (in bone marrow) were eradicated)

2-19-12 entry

Heading in a new direction: drug permeability in breast cancer brain metastasis (OPEN ACCESS)
http://clincancerres.aacrjournals.org/content/16/23/5605.long - http://clincancerres.aacrjournals.org/content/16/23/5605.long

2-23-12 entry

Researchers Reveal How Cancer Cells Change Once They Spread to Distant Organs

Cornell Center on the Microenvironment and Metastasis and Neuberger Berman Lung Cancer Research Center Findings Suggest Targeting a Single Protein May Help Stop Cancer Spread


http://weill.cornell.edu/news/releases/wcmc/wcmc_2012/02_22-12.shtml - http://weill.cornell.edu/news/releases/wcmc/wcmc_2012/02_22-12.shtml

Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition

http://cancerres.aacrjournals.org/content/early/2012/01/24/0008-5472.CAN-11-2905.abstract - http://cancerres.aacrjournals.org/content/early/2012/01/24/0008-5472.CAN-11-2905.abstract

2-24-12 entry

A monoclonal antibody targeting c-MET onartuzumab is in clinical trials for metastatic TNBC:
http://clinicaltrials.gov/ct2/show/NCT01186991?term=onartuzumab&rank=4 - http://clinicaltrials.gov/ct2/show/NCT01186991?term=onartuzumab&rank=4

2-25-12 entry

Should a Routine Metastatic Workup Be Performed for all Patients with Pathologic N2/N3 Breast Cancer?
http://www.ncbi.nlm.nih.gov/pubmed/22342788 - http://www.ncbi.nlm.nih.gov/pubmed/22342788
158 patients total, retrospective analysis, no breakout into TNBC.
CONCLUSIONS: A metastatic workup is only indicated for N2/N3 patients with T3 or T4 primary lesions.

2-28-12 entry

Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer
http://onlinelibrary.wiley.com/doi/10.1002/cncr.27434/abstract - http://onlinelibrary.wiley.com/doi/10.1002/cncr.27434/abstract
Retrospective study from MDA. Depressing conclusions.
CONCLUSIONS: Patients with nonmetastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort in which to research preventive strategies.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: ds21
Date Posted: Feb 09 2012 at 3:11pm
Open Access Publication bill introduced in Congress

If you are frustrated by not being able to read the full text of articles relevant to your care, write to your congressmen and tell them to support a newly introduced open access publication bill

http://doyle.house.gov/FRPA112FINAL.pdf - http://doyle.house.gov/FRPA112FINAL.pdf

David
http://doyle.house.gov/FRPA112FINAL.pdf -


-------------
Co-survivor


Posted By: Lee21
Date Posted: Feb 09 2012 at 5:15pm

Micrometastases and isolated tumor cells in the lymph nodes (and elsewhere)

Haven’t been able to find a lot of information specific to TNBC – in my opinion, the current data/views should apply at the very minimum to TNBC.

One study reports that almost a third of patients with T1 and T2 tumors already have dissemination to the bone marrow at the time of diagnosis (not subtyped) and another study pointed out that the presence of tumor cells in the bone marrow is not correlated with tumor cells in the lymph nodes.

Reviews:

Clinical significance of sentinel lymph node isolated tumor cells in breast cancer

http://www.ncbi.nlm.nih.gov/pubmed/21455668 - http://www.ncbi.nlm.nih.gov/pubmed/21455668

The role of micrometastatic disease in sentinel lymph node in breast cancer

http://onlinelibrary.wiley.com/doi/10.1111/j.1524-4741.2010.00999.x/abstract - http://onlinelibrary.wiley.com/doi/10.1111/j.1524-4741.2010.00999.x/abstract

Identification and biologic significance of micrometastases in axillary lymph nodes in patients with invasive breast cancer

http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-133.6.869 - http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-133.6.869

 

Evidence for prognostic importance of micromets in lymph nodes :

Micrometastases or isolated tumor cells and the outcome of breast cancer

http://www.nejm.org/doi/full/10.1056/NEJMoa0904832#t=articleTop - http://www.nejm.org/doi/full/10.1056/NEJMoa0904832#t=articleTop

(large Dutch study but patient makeup only 5% with grade 3 histology and 5.9% who were hormone receptor negative – no further breakdown, tumor size T1 mainly)

Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells

http://www.ncbi.nlm.nih.gov/pubmed/22183034 - http://www.ncbi.nlm.nih.gov/pubmed/22183034

(same Dutch group and same patient makeup)

 

Against:

Prognostic value of lymph node micrometastases in breast cancer: a multicenter cohort study

http://www.ncbi.nlm.nih.gov/pubmed/21153885 - http://www.ncbi.nlm.nih.gov/pubmed/21153885

(a different Dutch group, patients mostly T1-2 N0, 26.5% grade 3 tumors, no breakout into TNBC)

Impact of micrometastases in the sentinel node of patients with invasive breast cancer

http://jco.ascopubs.org/content/27/28/4679.long - http://jco.ascopubs.org/content/27/28/4679.long

(small study from Santa Monica, little stratification of patient population)

and rebuttal:

Micrometastases and isolated tumor cells in breast cancer are indeed associated with poorer outcome

http://jco.ascopubs.org/content/28/9/e140.long - http://jco.ascopubs.org/content/28/9/e140.long

Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer

http://jama.ama-assn.org/content/306/4/385.short - http://jama.ama-assn.org/content/306/4/385.short

(retrospective study, no breakout into TNBC, T1-2N0M0 invasive BC, results showed no survival association with occult mets in sentinel node but adverse association with occult mets in bone marrow)

 

Circulating tumor cells or tumor cells in bone marrow

See JAMA paper above

The influence of removal of primary tumor on incidence and phenotype of circulating tumor cells in primary breast cancer

http://www.springerlink.com/content/l473884m67218585/ - http://www.springerlink.com/content/l473884m67218585/

(prospective study of 209 patients pT1-4,pN0-2, M0, no neoadjuvant, 7% patients were TNBC, blood assayed 2-3 days post surgery.  Conclude 1) removal of primary tumor did not significantly influence tumor load in the blood stream; 2) most circulating tumor cells did not change phenotype before and after surgery)

Prognostic value of hematogenous dissemination and biological profile of the tumor in early breast cancer patients: a prospective observational study

http://www.biomedcentral.com/1471-2407/11/252 - http://www.biomedcentral.com/1471-2407/11/252

(small prospective study from Spain, 104 patients.  22% of patients had bone marrow tumor cells; 28% had axillary lymph node tumor cells and only 5 patients had tumor cells at both sites. TNBC patients (how many?) as expected had poorer disease-free survival but no statistical correlation found between bone marrow tumor cells and TNBC – maybe numbers too small)

Disseminated tumor cells predict survival after neoadjuvant therapy in primary breast cancer

http://onlinelibrary.wiley.com/doi/10.1002/cncr.26202/full - http://onlinelibrary.wiley.com/doi/10.1002/cncr.26202/full

(prospective study of 95 patients from MDA, 25% TNBC – 33% of T1 tumors and 27% of T2 tumors had bone marrow tumor cells detected after neoadjuvant. 26% patients had pCR but 25% of these patients still had bone marrow tumor cells.  These numbers were not associated with BC subtype.  Presence of BM tumor cells was a poor prognostic factor)

Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse--a European pooled analysis

http://clincancerres.aacrjournals.org/content/17/9/2967.short - http://clincancerres.aacrjournals.org/content/17/9/2967.short

(retrospective study of 676 women in Norway and Germany who had bone marrow aspirates during clinical followup after treatment when the patients were in remission. Patients were stage I-III. 122/676 patients were TNBC but findings were not broken out by subtypes. Takehome:  having tumor cells in bone marrow during remission is a sign of bad prognosis, particularly for those patients who received adjuvant therapy.)

2-29-12 entry

These results come from an update of the Phase III International Breast Cancer Study Group (IBCSG) trial 23-01. The study was reported at the San Antonio Breast Cancer Symposium (SABCS; abstract S3-1).

http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid+Tumors&d_id=148&i=February+2012&i_id=815&a_id=20214&c=Breast - http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid+Tumors&d_id=148&i=February+2012&i_id=815&a_id=20214&c=Breast

In patients with clinically node negative disease or minimally positive SNs, ALND may not be indicated.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: turtle
Date Posted: Feb 10 2012 at 10:48am
Lee, thanks for the recent posts, although they are a bit depressing. I agree with you about the need to see TNBC broken apart as its own beast. 

Part of the reason I brought up the issue about staging of TN tumors is because my onc initially told me that my node status would determine the number of cycles of chemo, but not necessarily change the actual drugs used. As I've become more informed about TNBC, I am less convinced that node status is of the same prognostic value for TN as it is for other subtypes of BC. Many of the articles you've sited bear this out, and it is an issue I will bring up with her when we meet on 2/13.

Here is a recent basic science article that may be of interest. It is essentially using pericyte (the smooth muscle cells that surround the endothelial cells of the vasculature, both normal and tumor-associated) coverage as an indicator of vessel integrity, and the lack thereof being an indicator of propensity for metastasis/decrease in OS:

http://www.ncbi.nlm.nih.gov/pubmed/22264789 - http://www.ncbi.nlm.nih.gov/pubmed/22264789
http://www.ncbi.nlm.nih.gov/pubmed/22264789# - Cancer Cell.  2012 Jan 17;21(1):66-81.

Pericyte Depletion Results in Hypoxia-Associated Epithelial-to-Mesenchymal Transition and Metastasis Mediated by Met Signaling Pathway.

http://www.ncbi.nlm.nih.gov/pubmed?term=Cooke%20VG%5BAuthor%5D -

Source

Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.



-------------
DX IDC TNBC 1/15/12 @ 46; MRI 2.4cm gr3 BRCA2+ 6174delT; LMX 1/31/12 2.5cm, pT2pNO(i)pMX, lymphovascular invasion present; 2/20/12 TAC X 6; 7/2/12 Rad X 25; 9/27/2012 2nd mastectomy & BSO surgery


Posted By: Charlene
Date Posted: Feb 10 2012 at 1:57pm

The discussion of prognosis reminds me of a series of columns that I read in the NYTimes, written by a doctor whose wife had been diagnosed with breast cancer.  At the end of treatment, they asked her doctor about her prognosis.  The doctor answered something like, "What percentage would make you change your life?"  For each of us, our chance of recurrence will either be 0% or 100%.  I was given about an 80% chance of being alive and without cancer in ten years.  Will I be part of that 80% or in the other 20%?  Who knows?  No one can answer that queston for me or for anyone else.  Statistics are only a small part of the story.  The best to all.

Charlene


-------------
DX 3/10 @59 ILC/TNBC
Stage 1, Grade 2, Multifocal; Lumpectomy/re-excision
SNB 0/4 nodes, BRCA-; Taxotere/Cytoxan X4, 30 rads
3/14:NED


Posted By: turtle
Date Posted: Feb 10 2012 at 2:26pm
Charlene,

Thank you for keeping it real. I think we all are just looking for reassurance that we'll be part of the 80%, and it's just my nature to over-analyze.


-------------
DX IDC TNBC 1/15/12 @ 46; MRI 2.4cm gr3 BRCA2+ 6174delT; LMX 1/31/12 2.5cm, pT2pNO(i)pMX, lymphovascular invasion present; 2/20/12 TAC X 6; 7/2/12 Rad X 25; 9/27/2012 2nd mastectomy & BSO surgery


Posted By: Charlene
Date Posted: Feb 10 2012 at 5:06pm

Turtle,

Actually, I was the exact same way for a long while.  I kept demanding answers from my doctors and wanted them to pronounce me "CURED."  I gradually learned to accept that that was never going to happen.  I do wish you the best!
 
Charlene 
 


-------------
DX 3/10 @59 ILC/TNBC
Stage 1, Grade 2, Multifocal; Lumpectomy/re-excision
SNB 0/4 nodes, BRCA-; Taxotere/Cytoxan X4, 30 rads
3/14:NED


Posted By: Lee21
Date Posted: Feb 10 2012 at 7:31pm
updated entry for imaging
Lymphatic drainage patterns from the breast
(trying to understand how local mets occur, particularly to the internal mammary nodes and other non-axilla nodes) -- how much is getting missed by focusing on just the axilla.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 11 2012 at 7:57pm
Low (1-9%) Hormone receptor expression

Estrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1% to 10% ER-Positive by Immunohistochemistry
http://www.ncbi.nlm.nih.gov/pubmed/22291085 - http://www.ncbi.nlm.nih.gov/pubmed/22291085
CONCLUSIONS: minority of the 1% to 9% IHC ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine-sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.
NOTE: The overall survival rate of 1%-9% ER+ patients was between those of patients in the >=10% ER+ and ER- (<1%) groups.

Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers
http://onlinelibrary.wiley.com/doi/10.1002/cncr.26431/abstract - http://onlinelibrary.wiley.com/doi/10.1002/cncr.26431/abstract
CONCLUSIONS: In this cohort, a low ER/PR level (1%-5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6% to 10% is seen. Benefit of endocrine therapy in these patients is unclear.

4-1-12 entry
Recommendations for ER positivity cutoff to be 1% (OPEN ACCESS)

http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.7.e48 - http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.7.e48
Scroll down to "What Are the Clinically Validated Methods That Can Be Used in This Assessment?" where the article discusses the basis for the recommendation (survival data)



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 14 2012 at 5:14pm
new entry under chemo in TNBC - weekly taxol

-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 14 2012 at 6:27pm
updated entry under timeline of TNBC subtypes - a repost from genome sequencing.

I think this will be a very important paper in terms of understanding the differences at the molecular level (mRNA expression) how TNBC is different from other subtypes


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 15 2012 at 12:16pm
Breast cancer associated genetic risks

19p13.1 is a triple negative-specific breast cancer susceptibility locus

http://cancerres.aacrjournals.org.ezproxyhost.library.tmc.edu/content/early/2012/02/11/0008-5472.CAN-11-3364.abstract - http://cancerres.aacrjournals.org.ezproxyhost.library.tmc.edu/content/early/2012/02/11/0008-5472.CAN-11-3364.abstract

The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.

Note this study only includes white women of European ancestry

Breast Cancer–Associated Abraxas Mutation Disrupts Nuclear Localization and DNA Damage Response Functions

http://stm.sciencemag.org/content/4/122/122ra23.abstract - http://stm.sciencemag.org/content/4/122/122ra23.abstract

http://health.usnews.com/health-news/news/articles/2012/02/22/researchers-spot-new-gene-mutation-linked-to-breast-cancer - http://health.usnews.com/health-news/news/articles/2012/02/22/researchers-spot-new-gene-mutation-linked-to-breast-cancer

Abraxas is part of the BRCA1 protein complex.
Only 4 cases (Finland) but the tumors are ER+ PR+ HER2-.  Mentioned that even with BRCA2 mutated tumors frequently show hormone receptor positivity.  So need more cases to see if TNBC is part of the spectrum.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Wade
Date Posted: Feb 15 2012 at 12:24pm
Wow - great find. It is nice to see research specifically tied to TN disease.

Wade


-------------
Wife DX 5/2011@52 2.5x3.1cm;6/2011 DD A/C 4x,Abraxane 4x; Lumpectomy, SN biopsy 10/2011; 10/27/2011 NED; Rads start 11-22-2011, Rads fin 1-11-2012; 10-2013 NED; 07-18-2014 NED; November 2018 NED


Posted By: Lee21
Date Posted: Feb 15 2012 at 6:20pm
new entry under TNBC chemo (GeparTrio trial)

-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Grateful for today
Date Posted: Feb 16 2012 at 1:09am
Additional articles on chemotherapy added to post of 2/6/12

Grateful for today........Judy


Posted By: Lee21
Date Posted: Feb 16 2012 at 9:11am
Judy
Thank you for the papers on DD - they look very pertinent.
Lee


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 16 2012 at 2:46pm
new entry under Avastin (biomarkers for patients who could benefit from Avastin)

-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 18 2012 at 9:10am
2-18-12 entry under breast conserving surgery

-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm



Print Page | Close Window

Forum Software by Web Wiz Forums® version 12.01 - http://www.webwizforums.com
Copyright ©2001-2018 Web Wiz Ltd. - https://www.webwiz.net