Triple-Negative Breast Cancer:Distinguishing between Basal and Nonbasal Subtypes

Purpose: Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers. Experimental Design: We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE-). Results: Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival. Conclusion: TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC

The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology

International audienceAlthough invasive ductal (IDC) and lobular (ILC) breast carcinomas are well characterised in the literature, the biological and clinical significance of mixed tumours with both ductal and lobular components has not been investigated. In the current study, we have examined a well-characterised series of breast carcinoma with a long term follow-up that comprised 140 mixed tumours, 2170 IDC and 380 pure ILC. Results: Mixed tumours constituted 3.6% of all cases. The majority (59%) of the mixed tumours were grade 2 compared to 33% in IDC and 88% in ILC. Positive lymph nodes (LN) were found in 41% and definite vascular invasion (VI) in 26% of the cases. DCIS was detected in 123 (89%) and LCIS in 43 (31%) (both DCIS and LCIS were found in 39 cases). The majority of tumours were predominantly (>50 of tumour area) of ductal type (57%). When compared to pure IDC, mixed tumours showed an association with lower grade, ER positivity and lower frequency of development of distant metastases. When compared to pure ILC, mixed tumours showed an association with higher grade, positive LN metastasis, VI and development of regional metastasis. After adjustment for grade most of these differences were no longer apparent. There was an association between histologic type of carcinoma in LN metastasis and the predominant histologic type of the primary tumour. Mixed tumours showed metastatic patterns similar to that of ILC with frequent metastasis to bone. No clinically meaningful differences in survival were found between these mixed carcinomas and pure IDC or ILC of the breast or between mixed tumours with predominantly ductal or lobular phenotype