BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received

BACKGROUND: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker. METHODS: Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2. RESULTS: In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66-0.88, P<0.001). BCL2 was a powerful prognostic marker in ER- (HR 0.63, 95% CI 0.54-0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48-0.65, P<0.001), and in HER2- (HR 0.55, 95% CI 0.49-0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57-0.85, P