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.
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.
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.
(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).
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.
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
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.
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.
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..
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.
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
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.
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).
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.
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.
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?
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.
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
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/ except that in that trial, treatment is modulated depending on outcome whereas the ISPY2 is not, for what reason I do not know.
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.
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 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.
“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.
3 A
and B). Luminal subtype C was associated with the worst outcome of the three
presumed subtypes when a six-subtype classification formed the basis for the
survival analysis (Fig. 3C).
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. 1D),
which suggests that the high level of expression of this set of genes is
associated with poor disease outcomes.”
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.
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
“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
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?
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.
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