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Letters to the Editor Emad Rakha Ian Ellis Department of Histopathology, Nottingham City Hospital NHS Trust, Nottingham University, Nottingham, United Kingdom Are Triple-Negative and Basal-Like Breast Cancer Synonymous? To the Editor: In a recent issue of Clinical Cancer Research, Dent and colleagues (1) have reported on the prognostic significance of estrogen negative, progesterone negative, and HER2 negative (triple-negative) class in a large cohort of breast cancer patients. Triple-negative tumors are undeniably one of the most relevant subgroups of breast cancer from a medical oncologist’s perspective, given the lack of targeted therapies for this group and their aggressive clinical behavior. We believe, however, that equating basal-like cancers to triple-negative tumors may be misleading because the basal-like category of tumors is composed almost entirely of triple-negative breast cancers (1). If expression profiling analysis using the intrinsic gene list is considered the ‘‘gold standard’’ for the identification of basal-like cancers, intuitively, one would claim that the majority of basallike cancers would lack hormone receptors and HER2 expression. In two studies in which the expression of hormone receptors were analyzed in tumors classified according to the intrinsic gene list, however, ER expression was seen in 5% to 45% of basal-like cancers. In addition, Rouzier and coworkers (2) have shown that 14% of basal-like cancers also express HER2. On the other hand, triple-negative tumors are not necessarily basal-like cancers. In fact, a significant proportion of normal breast – like cancers as defined by expression arrays would also lack hormone receptors and HER2. Although the latter group is still poorly characterized, they are reported to have a prognosis that seems to be better than that of basal-like cancers (3, 4) and do not seem to respond to neoadjuvant chemotherapy (2, 5). In fact, in one study, 45% of patients with basal-like cancer showed pathologic complete response after anthracycline + taxanes neoadjuvant chemotherapy, whereas none of the normal breast – like cancers did so (2). We (6) and others (7) have shown that the expression of basal markers (i.e., basal cytokeratins and epidermal growth factor receptor) identifies a clinically significant subgroup within the triple-negative group. On the other hand, expression of basal cytokeratins and/or epidermal growth factor receptor (6 – 8), regardless of the expression of estrogen or progesterone status, identifies a subgroup of cancers that persistently display a poor prognosis, even at 10 years. Caution should be exercised when using definitions based on the lack of expression markers. As stressed by Nielsen and colleagues (9), ‘‘lack of staining for estrogen and HER2 alone to identify basal-like breast cancers risks misassignment based on technical failures.’’ In fact, estrogen has a documented technical false-negative rate (10) and problems with HER2 interpretation, in particular, when data are retrieved from pathology reports without a central review, may lead to biased results (11). Clinical studies addressing triple-negative cancers are undeniably required; however, large-scale studies comparing the expression of estrogen, progesterone, and HER2 in cases classified as basal-like by expression arrays are required before we can safely say that a triple-negative phenotype can be used as an accurate surrogate for basal-like cancers. Clin Cancer Res 2008;14(2) January 15, 2008 Jorge Reis-Filho The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom References 1. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13:4429 ^ 34. 2. Rouzier R, Perou CM, Symmans WF, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005;11: 5678 ^ 85. 3. Fan C, Oh DS,Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 2006;355:560 ^ 9. 4. SorlieT, Perou CM,Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869 ^ 74. 5. Rody A, KarnT, Solbach C, et al. The erbB2+ cluster of the intrinsic gene set predicts tumor response of breast cancer patients receiving neoadjuvant chemotherapy with docetaxel, doxorubicin and cyclophosphamide within the GEPARTRIO trial. Breast 2007;16:235 ^ 40. 6. Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer 2007;109:25 ^ 32. 7. Tischkowitz M, Brunet JS, Begin LR, et al. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer 2007;7:134. 8. Abd El-Rehim DM, Pinder SE, Paish CE, et al. Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 2004;203:661 ^ 71. 9. NielsenTO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004;10:5367 ^ 74. 10. Rhodes A, Jasani B, Barnes DM, Bobrow LG, Miller KD. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol 2000;53:125 ^ 30. 11.Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007;25: 118 ^ 45. F 2008 American Association for Cancer Research. doi:10.1158/1078-0432.CCR-07-1943 618 www.aacrjournals.org Downloaded from clincancerres.aacrjournals.org on April 28, 2017. © 2008 American Association for Cancer Research. Are Triple-Negative and Basal-Like Breast Cancer Synonymous? Emad Rakha, Ian Ellis and Jorge Reis-Filho Clin Cancer Res 2008;14:618. Updated version Cited articles Citing articles E-mail alerts Reprints and Subscriptions Permissions Access the most recent version of this article at: http://clincancerres.aacrjournals.org/content/14/2/618.1 This article cites 11 articles, 6 of which you can access for free at: http://clincancerres.aacrjournals.org/content/14/2/618.1.full.html#ref-list-1 This article has been cited by 2 HighWire-hosted articles. Access the articles at: /content/14/2/618.1.full.html#related-urls Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at [email protected]. To request permission to re-use all or part of this article, contact the AACR Publications Department at [email protected]. Downloaded from clincancerres.aacrjournals.org on April 28, 2017. © 2008 American Association for Cancer Research.