EPIDEMIOLOGY Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers Sharon Nofech-Mozes Maureen Trudeau Harriet K. Kahn Rebecca Dent Ellen Rawlinson Ping Sun Steven A. Narod Wedad M. Hanna Received: 20 October 2008 / Accepted: 23 December 2008 / Published online: 3 February 2009 Ó Springer Science+Business Media, LLC. 2009 Abstract Traditional prognostic markers for breast can- cer include estrogen receptor (ER), progesterone receptor (ER) and HER2/neu. Negative staining for these three markers defines the ‘triple-negative’ phenotype. By adding markers for cytokeratin 5/6 and EGFR, triple-negative breast cancers can be divided into ‘basal-like’ and ‘normal- like’ subgroups. We conducted immuno-staining on a panel of 958 patients with breast cancer, using all five markers and we followed the patients for distal recurrence and death. We compared rates of distal recurrence in the basal-like and normal-like subgroups with that of women with ER-positive breast cancer. Only 16 of 958 women had normal-like breast cancers. These cancers resembled basal-like cancers in that they had a high proliferative index, but the women with normal-like breast cancers resembled ER-positive women in terms of distant recur- rence. The addition of CK5/6 and EGFR to the standard panel (ER/PR/HER2/neu) defines a small subgroup of women with normal-like breast cancer. The prognosis of these women may be superior to that of basal-like breast cancers but firm conclusions cannot be made. Keywords Triple-negative Á Basal-like Á Normal-like Á Breast cancer Á Prognosis Á Metastases Abbreviations ER Estrogen receptor PR Progesterone receptor Introduction Data from the profiling of genes expressed in breast cancer have lead to the generation of a new classification scheme with five subgroups: luminal A, luminal B, normal-like, Her2/neu positive and basal-like [1–3]. Several cohort studies have validated the clinical utility of the different subgroups, in terms of predicting distant recurrence and mortality [4, 5]. The term ‘basal-like’ reflects the similarity of the protein expression profile of this subgroup of cancers with that of the basal epithelial cells of the normal mam- mary gland, namely high expression of cytokeratins 5/6 and 17, laminin, EGFR and fatty acid binding protein 7 [6]. Basal-like breast cancers have been defined as those that are negative for estrogen-receptor (ER), progesterone- receptor and HER2/neu, but positive for keratin 5/6 or EGFR [7]. This is a subset of the traditional ‘triple-nega- tive’ category (i.e., negative for estrogen-receptor (ER), progesterone-receptor and HER2/neu). Breast cancers which are negative for all five markers are referred to as ‘normal-like’. It is of interest to know whether or not the sub-division of the triple-negative group of cancers into basal-like and normal-like subgroups is of clinical relevance; if so, this would require adding two immuno- histochemical stains to the standard panel of three. This investment might be justified if the proportion of non-basal, triple-negative cancers was substantial, and if the natural history and/or response to treatment of the basal and S. Nofech-Mozes Á H. K. Kahn Á W. M. Hanna Department of Pathology, Sunnybrook Health Sciences Center and University of Toronto, Toronto, ON, Canada M. Trudeau Á R. Dent Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Center and University of Toronto, Toronto, ON, Canada E. Rawlinson Á P. Sun Á S. A. Narod (&) Women’s College Research Institute, Women’s College Hospital and University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON M5G 1N8, Canada e-mail: steven.narod@wchospital.ca 123 Breast Cancer Res Treat (2009) 118:131–137 DOI 10.1007/s10549-008-0295-8