Neoadjuvant TN Article

FloridaLady · February 2009

This article shows shrinking tumors does not mean extending survival. In triple negatives neoadjuvant chemo caused less overall survival.

Neoadjuvant/presurgical treatments

Ian E Smith

Breast Cancer Research 2008, 10(Suppl 4):S24doi:10.1186/bcr2184

The electronic version of this article is the complete one and can be found online at: http://breast-cancer-research.com/content/10/S4/S24

Introduction

In this article the term 'neoadjuvant' is used to describe pre-operative treatment for 3 months or more for large (usually ≥ 3 cm) operable cancers before surgery. Clinical response and pathological response are important end-points. The term 'presurgical' refers to treatment of short duration (around 2 weeks) before surgery, sometimes referred to as a 'window of opportunity' study. This approach can be used for any size of cancer provided it can be core biopsied, and the endpoints are molecular markers.

Traditional goals of neoadjuvant therapy include the following:

to improve survival;
to downstage so that inoperable cancers become operable or so that conservative surgery can replace mastectomy;
to identify short-term clinical or molecular markers of response to predict long-term outcome as a prelude to (or as a substitute for) adjuvant trials;
to predict outcome and plan further treatment in the individual patient; and
to identify the molecular mechanisms that underlie response and resistance to treatment.

Short-term presurgical therapies can have similar aims with the proviso being that this treatment will not lead to downstaging and that clinical and pathological response rates are unrealistic end-points.

Current evidence suggests that there is no survival benefit from neoadjuvant chemotherapy [1]. The question has not thus far been addressed in a large neoadjuvant endocrine therapy trial. Neoadjuvant chemotherapy has been shown to downstage and reduce the need for mastectomy in some but by no means all women [1]. The same is true for neoadjuvant endocrine therapy; about 40% of mastectomies can be avoided with preoperative aromatase inhibitor therapy [2].

Short-term surrogate clinical and pathological markers for outcome

Clinical response

Clinical response is widely used as a primary or secondary end-point in current neoadjuvant chemotherapy trials. This, however, is misguided.

Table 1. End-points in current neoadjuvant chemotherapy trials

In our own series of 995 patients treated with neoadjuvant chemotherapy at the Royal Marsden Hospital, London, over the past 15 years, there was no significant correlation between clinical response (including clinical complete remission) and long-term disease-free survival or overall survival. Similar findings were reported for the National Surgical Adjuvant Breast and Bowel Project (NSABP)B-18 trial, in which 1,500 patients were randomly assigned to receive neoadjuvant or adjuvant chemotherapy [3]. In the subsequent NSABPB-27 trial, which involved almost 2,500 patients, neoadjuvant adriamycin/cyclophosphamide (AC) alone, four courses, was compared with the same treatment followed by docetaxel for four courses prior to surgery. The sequential arm achieved a significantly higher complete clinical remission rate than AC alone (64% versus 40%; P < 0.001) but there was no significant difference in survival [4,5].

In our own experience, neoadjuvant chemotherapy involving cisplatin or carboplatin achieved a significantly higher complete clinical remission rate in patients with triple negative breast cancer than in others (88% versus 51%; P < 0.005), but there was no improvement in overall survival, and indeed the triple negative group exhibited a trend toward inferior survival [6].

FloridaLady · February 2009

I don't know what I think about this article. I would like more info. Let me know if anyone see another article. I go looking also.

Flalady

FloridaLady · February 2009

Triple-Negative Invasive Breast Cancer: Adjuvant Treatment Choices After Lumpectomy

Posted 10/30/2007

Antonio C. Wolff, MD, FACP
Author Information

Question
A 68-year-old female was diagnosed with triple-negative invasive ductal breast cancer (grade 3 cells). She underwent a lumpectomy with axillar clearing that removed the original tumor (size, 1.5 cm). Another tumor with the same histology (size, 0.5 cm) was discovered and removed during the surgery. No node involvement or distant metastases were noted. What treatment should follow the surgery? What kind of chemotherapy? Radiotherapy? Both? What sequence?

Response from Antonio C. Wolff, MD, FACP
Associate Professor, Oncology Breast Cancer Program, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland

In view of the potential for false-negative results of ER/PR (up to 20%) and HER2 (up to 10%) tests when assays are performed by less experienced labs and the resulting risk of denying adjuvant therapy with antiestrogens and/or anti-HER2 therapy to patients who could be helped by them, my initial reaction when reviewing a pathology report like this is to touch base with the pathologist who performed the assays to make sure that the tumor is indeed triple-negative. In this specific patient, a description of a high-grade tumor (grade 3) makes a triple-negative diagnosis more plausible. Her staging takes into account the size of the largest tumor (1.5 cm) and the negative axillary clearing for a final diagnosis of stage 1 (pT1N0), albeit high-risk (high-grade, triple-negative).

The available data on lumpectomy alone without radiation therapy (RT) show an increased risk of locoregional recurrence (but similar overall survival) in stage 1 breast cancer but are limited to women over age 70 years with ER-positive disease who received adjuvant tamoxifen.^[1] Therefore, assuming reasonable health and resulting good life expectancy, I would encourage this patient to consider RT for completion of breast conservation, which will not only reduce the risk of locoregional recurrence but also potentially improve her overall survival.^[2] Along these lines, I would also offer some adjuvant chemotherapy. The Oxford Overview was recently updated in 2005-2006, and a preliminary oral report by Sir Richard Peto at the San Antonio Breast Cancer Symposium in December 2006 suggests an almost 6% absolute reduction in the risk of recurrence events at 15 years (~ 36% vs 42%, HR 0.78) favoring polychemotherapy vs no chemotherapy for women in the age group from 60-69 years. In fact, a survival analysis from the 2000 Oxford Overview^[3] showed a 20% reduction in the annual odds of death for women in the age group from 50-69 years who were treated with an anthracycline, which translated into a 4.4% absolute improvement in overall survival (79.4% vs 75%) after 15 years.

For this patient with a T1cN0, ER-negative, grade 3 tumor, and with an average comorbidity for age, Adjuvant! Online (http://www.adjuvantonline.com/) suggests a 65% chance of being alive at 10 years, a 19.2% risk of death from other causes, and a 15.8% risk of death due to breast cancer. In her case, Adjuvant! Online indicates a 3.7% reduction in the risk of death at 10 years with an anthracycline regimen like doxorubicin and cyclophosphamide (AC) for 4 cycles or of 4.1% with AC followed by a taxane. Therefore, my personal preference would be to proceed with RT for completion of breast conservation after several cycles of polychemotherapy. I would initially consider a regimen such as AC, but it would be reasonable also to offer an alternative regimen, such as docetaxel and cyclophosphamide^[4] if there are concerns about an increased risk of long-term cardiac toxicity (eg, history of hypertension, diabetes, etc.).

FloridaLady · February 2009

Optimizing Treatment of "Triple-Negative" Breast Cancer CME

Eric P. Winer, MD Erica L. Mayer, MD, MPH Disclosures

Introduction

The use of modern genomic techniques has significantly enhanced our understanding of breast cancer biology. Five distinct breast cancer tumor subsets have been recognized, including hormone receptor (HR)-positive luminal A and B, human epidermal growth receptor 2 (HER2)-positive, "normal"-like, and basal-like. This final group is frequently identified by conventional immunohistochemical techniques as "triple negative" because it lacks staining for estrogen receptor (ER), progesterone receptor (PR), and HER2. Triple-negative tumors, which often overexpress the epidermal growth factor receptor (EGFR) 1 and are positive for CK 5 and/or 6, are typically high grade and have a high risk of relapse within the first several years after initial diagnosis. Long-term follow-up^[1] of triple-negative cohorts has demonstrated a worse prognosis for the triple-negative subgroups than for those that are HR-positive. Given the differential outcomes for patients with this group of cancers, there is significant interest in better understanding the natural history of and best treatment for triple-negative disease; multiple presentations at the 2007 San Antonio Breast Cancer Symposium (SABCS) addressed this topic.

Classification and Prognosis

Several posters explored classification and prognosis of triple-negative disease. Conforti and colleagues^[2] attempted to characterize the use of immunohistochemical analysis in the identification of basal-like tumors. In their analysis of over 800 specimens from a single institution, triple-negative staining had positive and negative predictive values of 67% and 99%. This finding suggests that while not all triple-negative tumors are basal-like, non-triple-negative tumors are almost never basal-like.

Two posters examined outcomes in patients with small stage 1 triple-negative tumors. Kaplan and colleagues^[3] evaluated their institutional registry of over 800 patients with stage 1 disease. In general, those with triple-negative disease experienced more than 3 times the risk of recurrence compared with non-triple-negative patients, even after adjusting for tumor size and use of adjuvant chemotherapy. Similarly, a retrospective analysis^[4] of a small cohort of ≤ 1 cm triple-negative cancers demonstrated a significantly higher rate of recurrence (12.5%) compared with HR-positive or HER2-positive groups (1.3% and 7.4%, respectively, P = .007), despite increased use of adjuvant chemotherapy in the triple-negative subgroup.

Data on outcomes after metastatic recurrence were also presented. Dent and colleagues^[5] suggested triple-negative cancers not only were more likely to lead to distant recurrence and death than non-triple-negative cancers, but they also more often had visceral metastases as the first site of metastatic spread.

In general, these data supported previous observations while highlighting the need to optimize adjuvant therapies for this group of high-risk patients given the risks for recurrence and for visceral metastatic disease.

Treatment

Chemotherapy

Triple-negative tumors do not respond to endocrine agents or trastuzumab and can only be treated with chemotherapy. Fortunately, increasing evidence suggests that the triple-negative subgroup derives substantial and preferential benefit from chemotherapy. The Cancer and Leukemia Group B (CALGB)^[6] recently reviewed data from 3 randomized trials: 8541, investigating escalating dose intensity; 9344, exploring the addition of paclitaxel to the doxorubicin and cyclophosphamide (AC) backbone; and 9741, studying the impact of dose density. A combined analysis of over 6600 patients treated on these studies, stratified by HR status, demonstrated greater reductions in risk of recurrence for the HR-negative subset, translating into larger absolute benefits in both disease-free and overall survival.

The neoadjuvant setting also provides an opportunity to determine in vivo tumor responses to chemotherapy. The National Breast and Bowel Project (NSABP) B27 trial^[7] of neoadjuvant AC with neoadjuvant vs adjuvant taxane demonstrated a higher rate of pathologic complete response (pCR) in ER-negative rather than ER-positive tumors. Prospective analysis of outcomes after neoadjuvant chemotherapy stratified by molecular subtype has demonstrated that the "basal-like" group has a greater frequency of pCR compared with HR-positive/HER2-negative subgroups.^[8,9]

At the 2007 SABCS, several abstracts supported these findings. Four studies^[10-13] presented in poster format reported outcomes after exposure to neoadjuvant anthracycline ± taxane-containing regimens. In all 4 studies, pCR rates were significantly higher in the triple-negative subgroup compared with the HR-positive subgroups, with similarly high pCR rates in women with HER2-positive tumors.^[10-12] Among women with triple-negative tumors, the pCR rates were 23% to 36%. For trials with longer-term follow-up, inferior outcomes were observed among patients in the triple-negative group, especially in those with residual disease at surgery.^[13] Taken together, these outcomes demonstrate that not only is chemotherapy the primary choice of systemic therapy for triple-negative tumors, but it may also be a more efficacious choice.

With respect to the standard chemotherapy repertoire, some agents may be more effective than others in the treatment of triple-negative tumors. The newest chemotherapeutic agent available for treatment of metastatic breast cancer is ixabepilone, an epothilone analog. Epothilones bind tubulin, leading to stabilization of microtubules, cell cycle arrest, and subsequent apoptotic cell death; preclinical study has suggested activity in both taxane-sensitive and taxane-refractory tumors.^[14] In the primary phase 3 study leading to US Food and Drug Administration (FDA) approval,^[15] ixabepilone 40 mg/m² every 3 weeks plus capecitabine 2000 mg/m² were superior to capecitabine 2500 mg/m² monotherapy in 752 patients with anthracycline- and taxane-pretreated disease. A subgroup analysis was performed in the 25% of patients with triple-negative disease from the phase 3 study. In a group of 187 patients with triple-negative disease,^[16] response rate (RR) increased from 9% to 27% with the addition of ixabepilone to the capecitabine therapy, and progression-free survival (PFS) improved from 2.1 to 4.1 months (hazard ratio 0.68, 95% confidence interval 0.50-0.93). These relative improvements in RR and PFS were comparable to those seen in the study cohort as a whole, although the low RR of 9% with capecitabine monotherapy highlights the difficulty in treating this patient population. In the neoadjuvant setting, monotherapy with ixabepilone in patients with triple-negative tumors led to a pCR rate of 26%, comparable to that seen with other chemotherapeutics.^[17] Overall, ixabepilone appears to have reasonable activity in the triple-negative population.

Targeted Therapy

Bevacizumab. There has also been interest in the role of angiogenesis inhibitors in the treatment of triple-negative disease. Histologic examination of "basal-like" triple-negative tumors has demonstrated the presence of glomeruloid microvascular proliferation. These focal endothelial tufts, which portend a worse prognosis in node-positive breast cancer,^[18] may serve as targets for angiogenesis inhibitor therapy. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has a demonstrated role in the treatment of several solid malignancies. In breast cancer, bevacizumab was studied in the first-line metastatic setting in ECOG 2100, a phase 3 randomized study evaluating paclitaxel with or without bevacizumab in essentially HER2-negative patients.^[19] Overall results demonstrated a significant and persistent improvement in disease-free survival with the addition of bevacizumab. Subset analysis has demonstrated activity of the bevacizumab-containing arm in the sizeable triple-negative population, although results were statistically not different from those seen in the HR-positive subgroup. Ongoing studies with angiogenesis inhibitors will attempt to further elucidate the role of these agents in the triple-negative population.

Cetuximab. Triple-negative tumors are known to overexpress EGFR,^[20] and 2 studies presented at SABCS 2007 explored the role of cetuximab, a humanized monoclonal antibody directed against EGFR, in this tumor type. Both of the trials included a platinum agent because preclinical data suggested that triple-negative tumors may have defects in BRCA1-mediated DNA repair and thus may be sensitive to DNA-damaging agents such as platinums.^[21]

Carey and colleagues^[22] presented initial results from TBCRC 001, a phase 2 study that randomized patients with triple-negative stage IV breast cancer to either cetuximab monotherapy at 250 mg/m² or cetuximab combined with weekly carboplatin at AUC 2. This report described the results from an interim analysis of the monotherapy arm only. In the analysis, 21 patents were accrued; out of this group, 1 patient (4%) experienced a prolonged partial response, 4 patients (19%) had stable disease for at least 8 weeks, and the rest developed disease progression, some very quickly. Upon progression, 19 patients were crossed over to the combination therapy arm, wherein 4 (28%) had a partial response and 4 more had stable disease. Due to the low observed response rate with monotherapy, that arm was closed to further accrual; results from the combination arm are awaited.

O'Shaughnessy and colleagues^[23] also presented data on the use of cetuximab in a randomized phase 2 study of weekly irinotecan (90 mg/m²) and carboplatin (AUC 2), with or without cetuximab (250 mg/m²). In the overall intention-to-treat study population, response rate improved marginally from 28% to 33% with the addition of cetuximab. Approximately half of the study population (78 patients) had triple-negative tumors. In that subgroup, cetuximab was associated with a response rate of 49% compared with 30% when chemotherapy was used alone. No significant differences in PFS or overall survival were observed in any subgroup, and significant toxicity led to dose reductions in starting doses of the chemotherapy agents. Based on the available evidence, there is little reason to believe that either single-agent cetuximab or a small molecule tyrosine kinase inhibitor of EGFR will have substantial activity in the triple-negative setting. It remains unknown whether these agents will prove useful in this context when combined with chemotherapy.

Novel Approaches

Some of the newest work with triple-negative breast cancers is based on genomics. Jones and colleagues^[24] presented an evaluation of alphaVbeta6 expression, an integrin typically upregulated in processes such as wound healing, inflammation, and neoplasia, in both triple-negative and HER2-positive subgroups. Using a tissue database, the investigators demonstrated that alphaVbeta6 status proved a stronger predictor of reduced survival than ER-negative status. AlphaVbeta6-negative status was associated with a 10-year survival rate of 70% in the triple-negative group compared with 55% among those in the triple-negative group who are positive for alphaVbeta6. Multivariate analysis demonstrated this marker to be independent of traditional prognostic features such as size, grade, and lymph node status. Similar results were seen in an analysis by Osborne and colleagues^[25] that used immunohistochemistry of triple-negative tumor samples from a neoadjuvant study. Long-term evaluation for recurrence demonstrated that tumors with high levels of cyclin E pretreatment were at significantly higher risk of relapse compared with those with lower cyclin E. These results not only suggest diversity within the triple-negative subgroup but also possibly identify targets for novel therapy. It is expected that further work dissecting the category of triple-negative breast cancer will demonstrate further heterogeneity in this group and offer the opportunity for even more tailoring of therapy.

Ongoing trials are attempting to develop improved regimens for patients with triple-negative tumors. The PACS 08 study will examine the role of sequential adjuvant FEC-100 and ixabepilone specifically for triple-negative disease.^[26] An ongoing study in metastatic triple-negative breast cancer is evaluating the role of sunitinib antiangiogenesis monotherapy compared with best available chemotherapy.^[27] Other emerging targets for treatment incorporate components of cellular proliferative pathways, including the phosphoinositide 3-OH kinase pathway and the mitogen-activated protein kinase pathway, DNA repair, and growth-factor receptors such as EGFR and c-kit. Agents currently in phase 1/2 evaluation for triple-negative disease include dasatinib and PARP1 inhibitors. It is hoped that further advances in targeted treatment and optimization of chemotherapy will provide more effective treatment and improved outcomes for this aggressive subclass of breast cancer.

lemonpie · February 2009

Boy, not sure what to think either. I had neoaduvant chemo for both of my cancers..

FloridaLady · February 2009

***this says from what I understand is...TN ladies should not be using Adriamycin as first line of treatment if BRCA1 positive. Should be using Platnium drugs.

Are BRCA1 mutations a predictive factor for anthracycline-based neoadjuvant chemotherapy response in triple-negative breast cancers?

Sub-category:	Adjuvant Therapy
Category:	Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting:	2007 ASCO Annual Meeting

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Abstract No:	580
Citation:	Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 580
Author(s):	T. Petit, M. Wilt, J. Rodier, D. Muller, J. Ghnassia, P. Dufour, J. Fricker
Abstract:	Background: BRCA1 being involved in DNA repair and apoptosis, its mutations may influence response to chemotherapy. In vitro studies demonstrated that loss of BRCA1 function increased sensitivity to platinum compounds and induced resistance to anthracyclines. BRCA1-related breast cancers tend to be ductal carcinomas with high tumor grade, absence of hormonal receptors and no HER2 overexpression, so called triple-negative. We retrospectively analyzed anthracycline-based neoadjuvant chemotherapy efficacy in triple- negative tumors according to BRCA1 status. Methods: 393 breast cancer pts were treated with FEC100 neoadjuvant chemotherapy (FU 500 mg/m², epirubicine 100 mg/m², cyclophosphamide 500 mg/m²) between 1/2000 and 12/2006. Out of them, 14% had a triple-negative phenotype (55 pts). Patients with young age at diagnosis or family history of breast cancer were offered genetic testing for BRCA1 and BRCA2 mutations. Twelve of these patients had a BRCA1 deleterious mutation with a triple-negative tumor. Characteristics of these 12 pts at diagnosis were: median age = 38, tumor stage = 7 T2N0, 2 T2N1, 2 T3N0, 1 T3N1. Results: Pathological complete response was defined as absence of invasive tumor in breast and axillary nodes. After 6 cycles of FEC100, 42% of patients with triple-negative tumors (23/55) had a pathological complete response, compared to 17% (2/12) with a BRCA1 mutation. Only one of the 12 BRCA1 patients had an axillary node involvement. Conclusions: In our series, BRCA1 deleterious mutations decreased anthracycline-based chemotherapy efficacy in triple- negative breast cancers. Platinum compounds should be evaluated in these BRCA1-related tumors.

FloridaLady · February 2009

Magnetic Resonance Imaging in Predicting Pathological Response of Triple Negative Breast Cancer Following Neoadjuvant Chemotherapy

Jeon-Hor Chen

Center for Functional Onco-Imaging, University of California, Irvine, CA; Department of Radiology, China Medical University Hospital, Taichung, Taiwan

Rita S. Mehta

Department of Medicine, University of California, Irvine, CA

Philip M. Carpenter

Department of Pathology and Laboratory Medicine, University of California, Irvine, CA

Orhan Nalcioglu, Min-Ying Su

Center for Functional Onco-Imaging, University of California, Irvine, CA

To the Editor:

Triple-negative (TN) breast cancers account for approximately12% to 26% of all types of breast cancers.^1-5 TN tumors wereaggressive and were usually diagnosed at a later stage.⁵ Independentresearch data have demonstrated that TN breast cancer carriesa poor prognosis. Approximately 85% of TN phenotypic breastcancers are deemed to be basal-like and have a clinical behaviorsimilar to basal-like tumors.² Because of the lack of targetreceptors, there are still no specific chemotherapeutic agentsfor TN breast cancer until now. In June 20, 2007, issue of theJournal of Clinical Oncology, we reported on a patient withTN breast cancer, diagnosed during her pregnancy, whose diseaseshowed complete clinical response in magnetic resonance imaging(MRI) and pathological complete response (pCR) after receivingneoadjuvant chemotherapy (NAC) using anthracycline- and taxane-basedregimens.⁶ Using MRI, we have recently demonstrated that pCRin human epidermal receptor-2 (HER-2)-positive breastcancer can be predicted with a much higher accuracy rate thanfor HER-2-negative breast cancer (95% vs 50%).⁷ The roleof MRI inpredicting pCR and diagnosing residual tumor for TNbreast cancer following NAC is, however, not known.

In a full review of our breast MRI database from 2002 to 2006,29 patients with pathologically proven TN breast cancer (range,age 25 to 82 years; mean, 50 years) were found. The MRI studywas performed on a 1.5 T Phillips Eclipse MR scanner with astandard bilateral breast coil (Philips Medical Systems, Cleveland,OH). The study was approved by the institutional review boardand was compliant with the Health Insurance Portability andAccountability Act. All participants gave written informed consent.The diagnosis was made based on core biopsy (n = 27) or excisionbiopsy (n = 2). Fifteen of the 29 patients received NAC afterthe diagnosis, including four cycles of dose-dense AC (anthracycline[doxorubicin]-cyclophosphamide) followed by three cycles ofpaclitaxel (cremophor or albumin-bound paclitaxel) and carboplatin(both 3 weeks on, 1 week off; one cycle) plus or minus six dosesof bevacizumab every 2 weeks. All patients had pretreatmentbaseline breast MRI exams: at least two follow-up exams duringthe course of therapy, and a final examination after completingthe therapy protocol. Following NAC, a definitive surgery andpathologic examination of the breast specimen was performed.The residual disease post-NAC was recorded into one of threecategories: (1) no residual malignancy, no sign of cancer cells;(2) no residual invasive cancer, ductal carcinoma in situ present;(3) residual invasive cancer. Defined as no invasive cancerpresent, pCR includes categories (1) and (2). This definitionis used at The University of Texas M.D. Anderson Cancer Center(Houston, TX),⁸ and also at the National Cancer Institute meetingheld on March 26 to 27, 2007, entitled, "Preoperative Therapyin Invasive Breast Cancer." In cases with residual invasivecancer, the pathological size was determined as the longestdimension: either the longest dimension on one hematoxylin andeosin-stained slide or from the number of blocks (each5 mm) where the malignant invasive tumor was detected, whicheverwas greater.

The tumor size of each patient in all serial MRI studies (pretreatmentand all follow-up) was analyzed in one sitting by the radiologistto ensure consistent determination of the tumor boundary. Theradiologist was blind to the pathology results. If the one-dimensionalsize reduction after completing NAC was less than 30% comparedwith their pretreatment size, the case was classified as a nonresponder(NR). When residual tumor was present with greater than 30%size reduction, the case was classified as a partial response(PR). Cases in which no enhanced tissues were visible were classifiedas clinical complete response (CCR). When minimal enhancementwas found at the previous lesion site with weaker or comparableenhancement relative to normal glandular tissue (ipsilateralor contralateral), the case was classified as probable CCR.Both CCR and probable CCR were considered as CR determined onMRI (noted as MR-CR) and used to evaluate their accuracy inprediction of pCR.

For the 15 patients undergoing NAC, MRI diagnosed nine MR-CR,five PR, and one NR. Overall, the clinical response rate was93% (14 of 15 patients). Final pathology revealed pCR in ninepatients (nine of 15 patients; 60%), PR in five patients, andNR in one patient. MRI accurately predicted eight pCR (eightof nine patients; 89%) with one false-negative diagnosis. Forthe six non-pCR patients, MRI diagnosed five PR with one false-positivediagnosis. The size correlation between the MR^B and pathologyfor the five PR patients also showed highly correlated (r² =0.998).

Rouzier et al⁹ have shown that the TN tumor is more sensitiveto paclitaxel and doxorubicin-containing preoperativechemotherapy than the luminal and normal-like cancers. It wasshown that a complete pathological response rate was seen in45% of basal-like cancers and only 6% of luminal cancers. AnotherNAC study¹⁰ suggested that the clinical response rate to doxorubicinand cyclophosphamide was markedly higher in patients with TNbreast cancer than in those with non-TN subtype tumors (85%v 47%; P < .0001). Pathologic complete response to NAC wasalso higher in patients with TN tumors than in those with non-TNtumors (27% v 7%, P = .01). Using anthracycline and taxane-basedregimens, we have demonstrated even higher clinical responseand pCR rates than the other two studies previously described.

In our study, the role of MRI in predicting pCR and diagnosingresidual tumor for TN breast cancers following NAC was alsoimpressive. With more patients studied in the future, we believethat the definite role of MRI for TN tumors following NAC willbe clearer. If MRI can prove its high performance, it will helpbreast surgeons in planning conserving surgery more reliably.Since the final outcome following NAC was evaluated based onthe pathological findings and achieving pCR is considered theultimate goal for a favorable prognosis,^11-16 predicting pCRpreoperatively becomes an important issue and is associatedwith patient management and follow-up strategy. It was foundthat despite initial chemosensitivity, patients with the basal-likesubtype had worse distant disease-free survival and overallsurvival than those with the luminal subtype. However, the worseoutcome in basal-like subtype breast cancer was due to higherrelapse among those patients with residual disease after NAC.Only few patients with pCR had relapsed disease.

fightinhrd123 · February 2009

I have such bad chemo brain, these articles are way over my head I wonder if I did more damage than good now!! I had a complete response to chemo THEN surgery!! I figured chemo plays a bigger part in all this. Those that chemo works for have a better prognosis than those it doesnt, am i wrong? I am not triple neg, but my friend is, and we had the same response. Very confusing this whole BC thing, and I thought i was up on my studies Thanks for posting these though.

Laura

FloridaLady · February 2009

The last article says they can track TN cells after surgery with a MRI. Now I'm liking this.

Flalady

I'm with you Laura...I will try and go through these a point out the important parts. A lot of it just talking about TN.

FloridaLady · February 2009

FlaladyFrom what I understand this is saying...BRAC1 positve ladies should not be using Adimincyline but a Platnium chemo as first line of treatment.

Are BRCA1 mutations a predictive factor for anthracycline-based neoadjuvant chemotherapy response in triple-negative breast cancers?

Sub-category:	Adjuvant Therapy
Category:	Breast Cancer--Local-Regional and Adjuvant Therapy
Meeting:	2007 ASCO Annual Meeting




Abstract No:	580
Citation:	Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 580
Author(s):	T. Petit, M. Wilt, J. Rodier, D. Muller, J. Ghnassia, P. Dufour, J. Fricker
Abstract:	Background: BRCA1 being involved in DNA repair and apoptosis, its mutations may influence response to chemotherapy. In vitro studies demonstrated that loss of BRCA1 function increased sensitivity to platinum compounds and induced resistance to anthracyclines. BRCA1-related breast cancers tend to be ductal carcinomas with high tumor grade, absence of hormonal receptors and no HER2 overexpression, so called triple-negative. We retrospectively analyzed anthracycline-based neoadjuvant chemotherapy efficacy in triple- negative tumors according to BRCA1 status. Methods: 393 breast cancer pts were treated with FEC100 neoadjuvant chemotherapy (FU 500 mg/m², epirubicine 100 mg/m², cyclophosphamide 500 mg/m²) between 1/2000 and 12/2006. Out of them, 14% had a triple-negative phenotype (55 pts). Patients with young age at diagnosis or family history of breast cancer were offered genetic testing for BRCA1 and BRCA2 mutations. Twelve of these patients had a BRCA1 deleterious mutation with a triple-negative tumor. Characteristics of these 12 pts at diagnosis were: median age = 38, tumor stage = 7 T2N0, 2 T2N1, 2 T3N0, 1 T3N1. Results: Pathological complete response was defined as absence of invasive tumor in breast and axillary nodes. After 6 cycles of FEC100, 42% of patients with triple-negative tumors (23/55) had a pathological complete response, compared to 17% (2/12) with a BRCA1 mutation. Only one of the 12 BRCA1 patients had an axillary node involvement. Conclusions: In our series, BRCA1 deleterious mutations decreased anthracycline-based chemotherapy efficacy in triple- negative breast cancers. Platinum compounds should be evaluated in these BRCA1-related tumors.

FloridaLady · February 2009

How do you post and not get this returns? I tried to put it into Word first???

Flalady

FloridaLady · February 2009

chemotherapy may improve "triple-negative" tumor outcome By Laura Dean 11 November 2008 Ann Oncol 2008; 19: 1847-1852

MedWire News: Platinum-based chemotherapy achieves increased response rates for breast cancer patients with "triple-negative" (TN) tumors, UK researchers report.

"The term TN breast cancer describes those cancers which do not express estrogen receptor, progesterone receptor or over-express human epidermal growth factor receptor 2," explain Ian Smith and colleagues from the Royal Marsden NHS Foundation Trust in London.

"Treatment options for TN breast cancers are limited because of lack of targeted treatments."

To investigate suggestions that TN breast cancer may have increased sensitivity to platinum-based chemotherapy, Smith and team used their institution's breast unit database to identify 328 patients who had received platinum-based chemotherapy in a neoadjuvant, adjuvant, or metastatic setting.

Sixty-two (19%) of these patients had TN breast cancer. Neoadjuvant complete response rates were significantly higher for TN tumors (88%) than for other tumor types (51%). For patients with advanced breast cancer, overall response rates were 41% for TN tumors and 31% for others.

The 5-year overall survival rate for TN tumors following adjuvant or neoadjuvant chemotherapy was 64% compared with 85% for others. Five-year, disease-free survival for TN tumors was 57% compared with 72% for others.

The median progression-free survival time in patients with advanced TN tumors was significantly longer, at 6 months, than in patients with other tumor types, at 4 months, although overall survival was not significantly different between the two groups (11 vs 7 months).

Acknowledging the limitations of the study, Smith and co-authors comment: "The combination regimens in the neoadjuvant and adjuvant setting included anthracycline, another active agent; hence, it is difficult to know whether the response was to the anthracycline or the platinum salt or both."

However, they add in the Annals of Oncology: "Our results suggest that there may indeed be some clinical gain with platinum salt chemotherapy for TN tumors but if so it is likely to be modest."

Free abstract

tibet · March 2009

After reading this article, I get again scared with TN status. I don't have family history and is it likely I have BRCA1? This artcle seems to say TN has worse prognosis than ER+ or HER2 + in long term follow up and this contrictes with others saying TN having odds after 3 to 5yrs than other type.

And this article somewhere says:"The 5-year overall survival rate for TN tumors following adjuvant or neoadjuvant chemotherapy was 64% compared with 85% for others. Five-year, disease-free survival for TN tumors was 57% compared with 72% for others."

DO these figures include all stages or only early stages? So for early stage TN, is the 5 yr disease-free higher than 57%

What you gales all think?

Neoadjuvant TN Article

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