Substantial controversy exists about the prognostic role of molecular tumor subtypes in MaBC. It is mainly classified as a luminal disease, but survival differences between Luminal A and B are not clarified. The aim of this study was to assess the molecular subtype profiles of MaBC, and subsequently the clinical outcome, using two different approaches: mmunochemistry and the gene-expression profile PAM50.
A total of 69 cases of invasive MaBC, were examined using an immunohistochemical standard staining for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR) and Ki-67. Immunohistochemical subtypes were classified according to Cheang et al. (2009). Gene-expression profiling was performed on a research-use-only (RUO) nCounter Analysis System using the RUO PAM50 assay analyzed with the Prosigna® algorithm. The Kaplan-Meier method was used to estimate Overall Survival (OS).
Patients had a median age of 63 (range 23-92). The mean and median OS were 184 and 156 months, respectively. At diagnosis, patients were mainly stage I (27.5%) and II (40.6%). When subtyping by IHQ and PAM50, the majority of samples were luminal B (49.3% and 59.7%, respectively) followed by luminal A (44.3% and 29.9%). Only 5.8% by IHQ and 10.4% by PAM50 were non-luminal (1 basal-like, 2 non-basal triple negative and 1 Her2-enriched by IHQ and 7 Her2-enriched by PAM50). We found a strong association between both IHQ and PAM50 classifications (p-value = 0.007). There were no significant differences in OS between luminal A and luminal B subtypes, neither by immunohistochemistry (p = 0.22) nor in PAM50 subtypes (p = 0.89). However, Her2-enriched patients by PAM50 showed significant worse prognosis (p = 0.009).
The most common subtypes in our MaBC cohort were luminal B followed by luminal A. No differences were found between these tumor subtypes in terms of patient outcome. However, Her2-enriched patients by PAM50 showed worse prognosis. Further research with larger cohorts is needed to unveil the real role of the different subtypes in MaBC.
Clinical trial identification
Legal entity responsible for the study
Biomedical Research Institute of Malaga (IBIMA)-Hospital Universitario Regional y Virgen de la Victoria, Malaga (Spain)
All authors have declared no conflicts of interest.