BCL2 is a key factor for the regulation of cellular apoptosis and its overexpression inhibits apoptotic cell death and activates cellular proliferation, resulting tumor progression. BCL2 are expected to be associated with an adverse prognosis in solid tumor. However, studies have reported inconsistent results and some showed even favorable features in breast cancer, which can be analyzed according to the subtype. The aim of this study is to investigate characteristics of BCL2 by subtype and to find possible confounding factor leading to conflicting results in breast cancer.
Female patients with breast cancer who completed primary treatment against breast cancer between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. Clinocopathological characteristics including BCL2 expression were collected. Patients were categorized into two groups, BCL2 expression in more or less than 10% of tumor cells. Kaplan-Meier curves were generated to compare recurrence-free interval (RFI) and overall survival (OS).
The final cohort included 617 patients with a mean age of 54.79±11.2 (25-86) years. Patients did not show survival difference by BCL2 status(p=0.616). Patients showed opposite result of survival when they were divided by HER2 status. In patients with HER2-overexpressed disease, patients with high BCL2 expression showed poor prognosis with statistically significant difference(p=0.0021). This difference showed tendency in patients with ER-positive disease (p=0.297) and ER-negative disease (p=0.029). However, patients with HER2-negative disease, BCL2 overexpression showed discrepant result, better survival than patients with low BCL2 expression(p=0.009). This difference also maintained in patients with ER-positive (p=0.259) and negative disease(p=0.010).
BCL2 overexpression showed different contribution to the patients’ survival based on HER2 status. High BCL2 was poor prognostic factor in patients with HER2 overexpression, which was consistent with expected role of BCL2. However, BCL2 overexpression indicated better prognosis in patients with HER2-negative disease than who does not.
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