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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: 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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

Disseminated tumor cells in biologic subtypes of stage I-III breast cancer patients (open access)
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

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

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

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

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
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
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.


Edited by Lee21 - Feb 28 2012 at 11:54am
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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Post Options Post Options   Thanks (0) Thanks(0)   Quote ds21 Quote  Post ReplyReply Direct Link To This Post 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

David

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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: 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

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

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

 

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

(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

(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

(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

(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

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

(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/

(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

(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

(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

(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

In patients with clinically node negative disease or minimally positive SNs, ALND may not be indicated.



Edited by Lee21 - Feb 29 2012 at 2:27pm
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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Post Options Post Options   Thanks (0) Thanks(0)   Quote turtle Quote  Post ReplyReply Direct Link To This Post 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:

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.

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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Charlene Quote  Post ReplyReply Direct Link To This Post 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote turtle Quote  Post ReplyReply Direct Link To This Post 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Charlene Quote  Post ReplyReply Direct Link To This Post 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 
 
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Stage 1, Grade 2, Multifocal; Lumpectomy/re-excision
SNB 0/4 nodes, BRCA-; Taxotere/Cytoxan X4, 30 rads
3/14:NED
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
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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 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
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
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
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)



Edited by Lee21 - Apr 01 2012 at 5:21pm
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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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
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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 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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

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://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.



Edited by Lee21 - Feb 25 2012 at 10:04am
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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Post Options Post Options   Thanks (0) Thanks(0)   Quote Wade Quote  Post ReplyReply Direct Link To This Post 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
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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: Feb 16 2012 at 1:09am
Additional articles on chemotherapy added to post of 2/6/12

Grateful for today........Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 16 2012 at 9:11am
Judy
Thank you for the papers on DD - they look very pertinent.
Lee
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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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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
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