Subtype-specific prognostic impact of Bcl-2 in HER2-positive and HER2-negative breast cancer

Bcl-2, a key regulator of cellular apoptosis, is typically linked to adverse prognosis in solid tumors due to its inhibition of apoptotic cell death and promotion of cellular proliferation, leading to tumor progression. However, studies on Bcl-2 in breast cancer have shown inconsistent results, with some indicating favorable outcomes. This study aims to determine the subtype-specific role of Bcl-2 in breast cancer. Female breast cancer patients who completed primary treatment at Wonju Severance Hospital, Korea, from 2004 to 2018 were included. Clinicopathological characteristics, including Bcl-2 expression, were collected, and patients were classified based on Bcl-2 expression in more than or less than 10% of tumor cells. Kaplan-Meier curves compared recurrence-free interval (RFI) and overall survival (OS). The final cohort of 617 patients, with a mean age of 54.79 ± 11.2 years, showed no overall survival difference by Bcl-2 status (p = 0.616). In HER2-overexpressed patients, high Bcl-2 expression was linked to poor prognosis (p = 0.0021). This trend appeared in ER-positive (p = 0.297) and ER-negative (p = 0.029) subgroups. Conversely, in HER2-negative patients, Bcl-2 overexpression indicated better survival (p = 0.009), consistent in ER-positive (p = 0.259) and ER-negative (p = 0.010) subgroups. Bcl-2's impact on survival varies with HER2 status, showing poor prognosis in HER2-overexpressed and better prognosis in HER2-negative patients.