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Lee21 View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Mar 31 2012 at 11:25am
annotated highlights from review previously posted under chemo in TNBC
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Apr 02 2012 at 5:43pm
updated entry on collection of reviews on TNBC....
http://forum.tnbcfoundation.org/topic9440_post95496.html#95496
free reviews and breast cancer virtual issue
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Apr 16 2012 at 9:01pm
Posted article on page 4:
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      

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Aug 02 2012 at 8:09pm
As usual, I was looking for something and found something else. Hence, the following:

Posted the following on page 4:

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

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

International Journal on Breast Cancer.    2012.   72 articles on breast cancer.
http://www.hindawi.com/journals/ijbc/contents/    (Table of 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/
-      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/
-      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/
-      Advancements in the treatment of metastatic breast cancer.
        Massimo Cristofanilli, MD
        http://downloads.hindawi.com/journals/jo/2012/703858.pdf
-      and there are other articles on TNBC. See above table of contents link.

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

Edited by Grateful for today - Aug 02 2012 at 10:03pm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Aug 04 2012 at 12:12pm
Following posted on page 4:

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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Aug 06 2012 at 10:31pm
Following posted on page 4:

Cancer Legal Resource Center.
Contact the CLRC (Cancer Legal Resource Center)
     http://www.lls.edu/academics/candp/clrc.html
     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)

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Aug 15 2012 at 7:48am
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Originally posted by Lee21 Lee21 wrote:

Novel therapeutics and targets for Breast Cancer

Cabozantinib, an inhibitor of two tyrosine kinase receptors: c-MET and VEGFR2

http://www.newscientist.com/article/dn21516-new-cancer-drug-sabotages-tumours-escape-route.html

So far, trials in prostate cancer only but studies in mouse model for breast cancer suggests efficacy:
Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth
http://www.ncbi.nlm.nih.gov/pubmed/21926191

Cabozantinib has been shown to be effective in pre-clinical studies of several different cancers.

Another monoclonal antibody targeting c-MET onartuzumab is in clinical trials for metastatic TNBC:
http://clinicaltrials.gov/ct2/show/NCT01186991?term=onartuzumab&rank=4

From Turtle:

This paper describes the use of mTor inhibitors in breast and ovarian cancer models, and is relevant because of ongoing (or canceled?) clinical trials using an mTor inhibitor in breast cancer (not sure if TN was broken out). The paper essentially concludes that they get the best effect when they use a combination of an mTor inhibitor and a Bcl2 inhibitor.
http://www.ncbi.nlm.nih.gov/pubmed/22340595 

I brought up this paper on a previous thread about lymphovascular invasion, since it essentially claims that using pericyte coverage is an important prognostic indicator of systemic recurrence. It is also important because it suggests that use of single agent tyrosine kinase inhibitors can paradoxically shrink the primary tumor, while promoting metastasis by upregulating hypoxia in the primary tumor, thereby driving EMT by upregulating cMet expression. Again, I think there have been several clinical trials (that may be suspended) using various tyrosine kinase inhibitors for breast cancer (but maybe only in the metastatic setting?).

A related paper suggesting similarly that antiangiogenic therapies such as sunitinib (tyrosine kinase inhibitor) or bevacizumab (VEGF antibody) increase hypoxia thereby upregulating cancer stem cells comes to similar conclusions, in that drugs targeting specific kinases be used in combination therapy, rather than monotherapy.

Subtype and pathway specific responses to anticancer compounds in breast cancer (OPEN ACCESS)
http://www.pnas.org/content/109/8/2724.long

3-19-12 entry
Myc pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition
http://jem.rupress.org/content/early/2012/03/13/jem.20111512
-- results from the original ISPY trial.
33 out of 36 TNBC tumors had a high-intermediate Myc gene signature score, correlating with worse outcome : diminished disease-free survival in patients whose tumors exhibited poor response to neoadjuvant treatment.
Increased Myc expression makes tumor cells more sensitive to CDK inhibition.  CDK = cyclin dependent kinase consists of a group of kinases that function in the cell cycle.  They tested 2 CDK inhibitors, one dinaciclib is in phase 2 trial for different cancers.

3-29-12 entry

Drug candidates derailed in case of mistaken identity

PARP inhibitor that wasn't highlights widespread flaws in preclinical studies.

http://www.nature.com/news/drug-candidates-derailed-in-case-of-mistaken-identity-1.10341

Found this article on Tyrosine Kinase Inhibitors and thought it could be added to the discussion above.

New class of proteins allows breast cancer cells to evade Tyrosine Kinase Inhibitors 

Aberrant regulation of cell growth pathways is required for normal cells to become cancerous, and in many types of cancer, cell growth is driven by a group of enzymes known as receptor tyrosine kinases (RTKs). The RTK epidermal growth factor receptor (EGFR) is overexpressed in over 30% of breast cancers; however, drugs that target RTKs, known as tyrosine kinase inhibitors (TKIs) have not been effective in treating breast cancer. Researchers believe that the cancer cells escape TKIs by circumventing the RTKs and utilizing other enzymes that are not TKI-sensitive. 

In the current issue of the Journal of Clinical Investigation, two groups identify a pair of related oncogenes, FAM83A and B, which allow breast cancer cells to survive TKI treatment. Researchers led by Mina Bissell at the Lawrence Berkeley National Laboratory in Berkeley, CA performed a screen of human breast cancer cell lines to identify genes that make cancer cells resistant to EGFR TKIs. Bissell and colleagues determined that increased expression of FAM83A increases proliferation and invasion, while decreased expression delays tumor growth in mice and renders cancer cells sensitive to TKIs. At Case Western Reserve Medical School in Cleveland, OH, Mark Jackson and colleagues identified FAM83B as a gene that allows normal human mammary cells to become malignant. Further, expression of FAM83A and B in human tumors was correlated with decreased overall survival. Taken together, these studies identify two genes that may serve as novel therapeutic targets. In a companion piece, Steven Grant of the Medical College of Virginia discusses the impact of this research on the development of strategies to overcome resistance to currently available TKIs. 

TITLE: FAM83B mediates EGFR- and RAS-driven oncogenic transformation 
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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Aug 29 2012 at 7:00pm
Following posted on p.4:

Thin Red Line’ Around Breast Cancer
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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Aug 30 2012 at 8:06pm
Following posted on p. 4:

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
Ecancermedicalscience. 2011; 5: 217.
Published online 2011 July 19. doi: 10.3332/ecancer.2011.217
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223951/

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Nov 12 2012 at 12:07pm
Following posted on p.4:

Triple-negative breast cancer in focus: From biology to novel therapeutics
In "Annals of Oncology" Volume 23 suppl 6 August 2012:
http://annonc.oxfordjournals.org/content/23/suppl_6.toc
Using the above link, all below articles have   free full text.
Articles are research articles and mostly European authors.

Editorial
M.J. Piccart: Editorial
Ann Oncol (2012) 23(suppl 6): vi5-vi6 doi:10.1093/annonc/mds186

Research articles

P. Boyle
Triple-negative breast cancer: epidemiological considerations and recommendations
Ann Oncol (2012) 23(suppl 6): vi7-vi12 doi:10.1093/annonc/mds187

C. Criscitiello, H. A. Azim, Jr, P. C. Schouten, S. C. Linn, and C. Sotiriou
Understanding the biology of triple-negative breast cancer
Ann Oncol (2012) 23(suppl 6): vi13-vi18 doi:10.1093/annonc/mds188

F. Penault-Llorca and G. Viale
Pathological and molecular diagnosis of triple-negative breast cancer: a clinical perspective
Ann Oncol (2012) 23(suppl 6): vi19-vi22 doi:10.1093/annonc/mds190

B. E. Dogan and L. W. Turnbull
Imaging of triple-negative breast cancer
Ann Oncol (2012) 23(suppl 6): vi23-vi29 doi:10.1093/annonc/mds191

W. Eiermann and K. A. Vallis
Locoregional treatments for triple-negative breast cancer
Ann Oncol (2012) 23(suppl 6): vi30-vi34 doi:10.1093/annonc/mds192

G. von Minckwitz and M. Martin
Neoadjuvant treatments for triple-negative breast cancer (TNBC)
Ann Oncol (2012) 23(suppl 6): vi35-vi39 doi:10.1093/annonc/mds193

H. Joensuu and J. Gligorov
Adjuvant treatments for triple-negative breast cancers
Ann Oncol (2012) 23(suppl 6): vi40-vi45 doi:10.1093/annonc/mds194

F. André and C. C. Zielinski
Optimal strategies for the treatment of metastatic triple-negative breast cancer with currently approved agents
Ann Oncol (2012) 23(suppl 6): vi46-vi51 doi:10.1093/annonc/mds195

M. Aapro and H. Wildiers
Triple-negative breast cancer in the older population
Ann Oncol (2012) 23(suppl 6): vi52-vi55 doi:10.1093/annonc/mds189

J. Crown, J. O'Shaughnessy, and G. Gullo
Emerging targeted therapies in triple-negative breast cancer
Ann Oncol (2012) 23(suppl 6): vi56-vi65 doi:10.1093/annonc/mds196
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Nov 12 2012 at 3:04pm
Cancer survivorship -- a full issue in the Journal of Clinical Oncology:
http://jco.ascopubs.org/content/30/30.toc
Alas, not open access.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Nov 12 2012 at 3:09pm
Adjuvant chemo or not??
See following article http://jco.ascopubs.org/content/30/31/3800.abstract

Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study

  1. Dawn L. Hershman

+ Author Affiliations

  1. Alfred I. Neugut, Wei Yann Tsai, Judith S. Jacobson, and Dawn L. Hershman, College of Physicians and Surgeons, Columbia University; Alfred I. Neugut, Grace Clarke Hillyer, Nicole Leoce, Wei Yann Tsai, Judith S. Jacobson, and Dawn L. Hershman, Mailman School of Public Health, Columbia University, New York; Christine B. Ambrosone, Roswell Park Cancer Institute, Buffalo; Carol Magai, Long Island University, Brooklyn, NY; Lawrence H. Kushi, Kaiser Permanente of Northern California, Oakland, CA; Lois Lamerato and S. David Nathanson, Henry Ford Health System, Detroit, MI; Dana H. Bovbjerg, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, PA; and Jeanne S. Mandelblatt, Georgetown University Medical Center, Washington, DC.
  1. Corresponding author: Alfred I. Neugut, MD, PhD, Division of Medical Oncology, Columbia University Medical Center, 722 W 168th St, Room 725, New York, NY 10032; e-mail: ain1@columbia.edu.

Abstract

Purpose For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors.

Patients and Methods We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years.

Results Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor– and progesterone receptor–negative status) were associated with increased chemotherapy initiation.

Conclusion Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.


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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Nov 12 2012 at 9:08pm
PI3-kinase inhibitors in TNBC:

New treatment option possible for triple-negative breast cancers

11/12/2012 – The simultaneous inhibition of two separate and seemingly unrelated pathways could potentially provide an effective treatment for women with triple-negative breast cancer, according to results of two studies published in the November issue of Cancer Discovery, a journal of the American Association for Cancer Research.

Triple-negative breast cancers do not express three common targets of breast cancer treatments: the estrogen receptor, progesterone receptor and HER2/neu. As a result, women with triple-negative breast cancer have few treatment options. In early-phase clinical studies, those women with triple-negative breast cancer with BRCA1 gene mutations had some clinical benefit from treatments with poly-ADP-ribose-polymerase (PARP) inhibitors. However, the activity of the PARP inhibitors is short-lived.

“We are in desperate need of new therapies for triple-negative breast cancer, which is a type of breast cancer that is very aggressive and occurs mostly in young females,” said José Baselga, M.D., Ph.D., chief of the division of hematology and oncology at Massachusetts General Hospital Cancer Center in Boston.

In their study, Baselga; Yasir Ibrahim, Ph.D., a postdoctoral fellow at Vall D’Hebron Institute of Oncology in Barcelona, Spain; and Maurizio Scaltriti, Ph.D., faculty assistant and lab coordinator at Massachusetts General Hospital Cancer Center, hypothesized that inhibiting PI3-kinase, a key component of a signaling pathway frequently activated inappropriately in triple-negative breast cancer, would replicate the conditions present in BRCA-mutated breast cancers, thereby increasing sensitivity to PARP inhibitors.

They found that if PI3-kinase function was blocked in a BRCA-proficient triple-negative breast cancer cell line, DNA damage would occur due to BRCA protein downregulation, and that this resulted in activation of PARP to repair the damage.

“In a way, with PI3-kinase inhibitors, we are converting BRCA-proficient triple-negative breast cancer into BRCA-deficient breast cancer and, therefore, these cells become sensitive to PARP inhibition,” Baselga said.

In the second study, Lewis C. Cantley, Ph.D.; Gerburg Wulf, M.D., Ph.D.; and colleagues used an endogenous mouse model of BRCA1-deficient breast cancer. They observed that mice with a BRCA1 mutation also had molecular indicators of strong activation of the PI3-kinase pathway, suggesting that the tumors might be vulnerable to PI3-kinase inhibitors.

When the mice were treated with a PI3-kinase inhibitor, tumor doubling was delayed from five to 26 days. Given that BRCA-mutated tumors are also known to respond to PARP inhibitors, the researchers combined the two medications and found that this delayed tumor doubling to more than 70 days.

“We saw in vivo synergy that led to dramatic prolongation of progression-free survival in these mice of more than two to three months, which in the life of a mouse is very long,” said Wulf, staff physician in the division of hematology and oncology at Beth Israel Deaconess Medical Center. “This is an unusual observation that makes us hopeful that it is worthwhile to explore in an early-phase clinical trial.”

Both studies received funding from Stand Up To Cancer Dream Team Translational Research Grants.

Cantley, who conducted the research while director of the cancer center at Beth Israel Deaconess Medical Center in Boston, and his colleagues have worked with Novartis and AstraZeneca, the two companies that manufacture the PI3-kinase inhibitor (BKM120) and the PARP inhibitor (Olaparib) to initiate a clinical trial combining the two drugs in humans.

Cantley said it is extremely unusual for two unapproved drugs to be combined in a cancer clinical trial, especially when the two drugs are produced by separate companies. Yet the preclinical results were sufficiently compelling to accelerate the initiation of this trial. The trial, led by Ursula Matulonis, M.D., director of medical gynecologic oncology at the Dana-Farber Cancer Institute in Boston, is now open and starting to enroll patients with triple-negative breast or ovarian cancer.

“This is truly an amazing story where essentially the same week that the paper is coming out showing an observation, the clinical trial is starting,” Cantley said. “This type of bench-to-bedside process typically takes five to 10 years but was dramatically accelerated by the collaborative efforts of the Stand Up To Cancer-funded PI3-Kinase Dream Team.”




Edited by Lee21 - Nov 12 2012 at 9:13pm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Nov 30 2012 at 11:48pm
Posted on p.4

REVIEW ARTICLE
New Insights and Emerging Therapies for Breast Cancer Brain Metastases
By Elgene Lim, MD, PhD, Nancy U. Lin, MD | July 12, 2012
Women’s Cancers Program, Dana-Farber Cancer Institute, Boston, Massachusetts

http://www.cancernetwork.com/breast-cancer/content/article/10165/2088901?pageNumber=1
http://www.cancernetwork.com/breast-cancer/content/article/10165/2088901?pageNumber=2

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Dec 01 2012 at 2:19pm
Posted on p.4 of this thread.

"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

http://journals.lww.com/oncology-times/blog/HowDoITreat/pages/post.aspx?PostID=20
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Jan 30 2013 at 1:28pm
Emerging targeted therapies in triple-negative breast cancer

http://annonc.oxfordjournals.org/content/23/suppl_6/vi56.full


Annals of Oncology (2012) 23 (suppl 6): vi56-vi65
J. Crown, J. O'Shaughnessy and G. Gullo


For some reason, I am now unable to update previous posts.



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Post Options Post Options   Thanks (1) Thanks(1)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Jan 30 2013 at 2:07pm
Tried to update above post but got an error message.

Judy had posted the above article previously -- here to point out that it is a rare free review of some of the newest treatment options in TNBC.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Jan 30 2013 at 5:19pm
Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial

http://www.sciencedirect.com/science/article/pii/S1470204512705259

Findings

Enrollment took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90–126), disease-free survival was 62% (95% CI 58–65) for patients in the TAC group and 55% (51–59) for patients in the FAC group (hazard ratio


0·80, 95% CI 0·68–0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72–79) for patients in the TAC group and 69% (65–72) for patients in the FAC group (HR 0·74, 0·61–0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3–4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC.

Interpretation

Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation.


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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 11 2013 at 3:22pm
Metastatic TNBC: mechanism and potential new target.

http://www.jci.org/articles/view/65416

TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer.

J. Clin. Invest.  ePub Feb. 8, 2013

After an initial response to chemotherapy, many patients with triple-negative breast cancer (TNBC) have recurrence of drug-resistant metastatic disease. Studies with TNBC cells suggest that chemotherapy-resistant populations of cancer stem-like cells (CSCs) with self-renewing and tumor-initiating capacities are responsible for these relapses. TGF-β has been shown to increase stem-like properties in human breast cancer cells. We analyzed RNA expression in matched pairs of primary breast cancer biopsies before and after chemotherapy. Biopsies after chemotherapy displayed increased RNA transcripts of genes associated with CSCs and TGF-β signaling. In TNBC cell lines and mouse xenografts, the chemotherapeutic drug paclitaxel increased autocrine TGF-β signaling and IL-8 expression and enriched for CSCs, as indicated by mammosphere formation and CSC markers. The TGF-β type I receptor kinase inhibitor LY2157299, a neutralizing TGF-β type II receptor antibody, and SMAD4 siRNA all blocked paclitaxel-induced IL8 transcription and CSC expansion. Moreover, treatment of TNBC xenografts with LY2157299 prevented reestablishment of tumors after paclitaxel treatment. These data suggest that chemotherapy-induced TGF-β signaling enhances tumor recurrence through IL-8–dependent expansion of CSCs and that TGF-β pathway inhibitors prevent the development of drug-resistant CSCs. These findings support testing a combination of TGF-β inhibitors and anticancer chemotherapy in patients with TNBC.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 14 2013 at 11:45am

Further subclassification of breast cancer tumors needed to help identify new biomarkers

DURHAM, NC — Breast cancers that are typically classified as triple-negative are in fact biologically heterogeneous and should be further classified into distinct molecular subtypes, according to a comprehensive study of breast cancer datasets.

The study, which will be published in the February issue of The Oncologist, was conducted by a team of scientists from the University of North Carolina at Chapel Hill and the Vall d’Hebron Institute of Oncology in Barcelona, Spain.

Previous research had identified four main subtypes of breast cancer: luminal A, luminal B, HER2-enriched and basal-like. Basal-like cancer has become more commonly known as triple-negative breast cancer to define breast cancers that lack expression of hormone receptors and overexpression and/or amplification of HER2 – even though up to 30 percent of tumors identified as triple-negative do not actually fall into the basal-like subtype category.

The study examined more than 1,700 samples from 12 publicly available datasets, and highlighted the following findings:

  • Triple-negative and basal-like definitions should not be considered synonymous because considerable discordance exists.
  • Triple-negative disease is a heterogeneous clinical entity composed of all the intrinsic molecular subtypes, with the basal-like tumors being the most frequent (70%).
  • Triple-negative tumors that are identified as non-basal-like (such as HER2-enriched or luminal A/B) show nearly undistinguishable global gene expression patterns versus non-triple-negative tumors that are HER2-enriched or luminal A/B.
  • Basal-like tumors that are non-triple-negative show similar genomic features, and an association with young age at diagnosis, as do basal-like tumors that are triple-negative.
  • Previously described triple-negative heterogeneity in part reflects known intrinsic subtype biology and microenvironmental heterogeneity.

“Our findings have very important implications for clinical trials focused on triple-negative breast cancers,” said corresponding author Dr. Charles Perou, Ph.D., of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill. “Future clinical trials focused on triple-negative breast cancers should consider stratifying patients based on basal-like versus non-basal-like gene expression profiles, which appear to be the main biological difference seen in patients with triple-negative breast cancer. In addition, our findings argue for very rigorous hormone receptor and HER2 testing due to the known reproducibility issues associated with these pathology-based biomarkers.”

Perou and his colleagues suggest that recognizing the molecular diversity of triple-negative tumors and subclassifying them as separate entities could support efforts to identify new biomarkers, which might possibly result in tests for subtype specific responses to different treatments, and conduct more targeted research on the clinical importance of the various molecular subtypes.

"The last decade has seen an increasing emphasis on subtyping of common cancers such as breast cancer. Multiple assays have been devised that help oncologists determine prognosis of particular subsets. However, as we move into routine clinical use of these assays, the current study reminds us that there is more work to do in this complex field especially if we are to use molecular assays to help change therapy and predict outcomes," said Shelley Earp, M.D., Director of the UNC Lineberger Comprehensive Cancer Center.


Link to actual paper:

http://theoncologist.alphamedpress.org/content/early/2013/01/30/theoncologist.2012-0397.abstract

For those so inclined, you can retrieve the article for free as soon as you create an account (free).

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
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