Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

Abstract

PurposeWe aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer.MethodsWe analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67.ResultsRegarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(–) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(–)/HER2(+) and HR(–)/HER2(–) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(–) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(–), HR(+)/HER2(+), and HR(–)/HER2(–) subtypes, but not in HR(–)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression.ConclusionThe prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(–) or luminal A and luminal B/HER2(–) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2.

ABT-737 ameliorates docetaxel resistance in triple negative breast cancer cell line

“…Since then, its association with a variety of neoplasms including breast cancer has been reported. We have previously reported that Bcl-2 expression is positive in 68.2% of unselected breast cancer patients [ 6 ] and 39.8% of TNBC patients [ 7 ]. Although many studies have reported the prognostic role of Bcl-2 in breast cancer [ 8 9 ], the mechanism of action involved remains unclear.…”

DNA fragmentation factors 40 and 45 (DFF40/DFF45) and B-cell lymphoma 2 (Bcl-2) protein are underexpressed in uterine leiomyosarcomas and may predict survival

“…This methodology is widely accepted and has been employed by many other studies for investigating the expression of DFF45 and Bcl-2. 25 – 29 , 32 As complete inter-rater agreement was achieved, the intra-rater disparity was the only potential bias in our sample assessment. However, as this disparity showed an almost-perfect correlation, intra-rater bias can safely be excluded.…”

“…According to Hwang et al, Bcl-2 expression was a strong favorable prognostic factor in the HR(+)/HER2(−) subtype of breast cancer and a marginally significant favorable prognosticator in the HR(+)/HER2(+), but had no prognostic impact on other subtypes. 29 In contrast, no significant correlation was seen between Bcl-2 expression and clinicopathological parameters of colorectal cancer. 26 Lack of Bcl-2 expression was also shown to be an independent predictor of poor prognosis in endometrial cancers.…”

Correlation of BCL-2 and ERα mRNA Expression with the Clinical Chemotherapeutic Response in Breast Cancer

“…The BCL-2 expression differs according to the molecular subtype and is only a useful prognostic marker for luminal A breast cancer 24 . The prognostic influence of BCL-2 was also different across molecular subtypes of breast cancer and was dependent on HR, HER2 and Ki-67expression as well as tumor stage 25 .…”