Different Prognostic Significance of Bcl-2 Based on Cancer Molecular Subtype

Abstract

Purpose: B-cell lymphoma (bcl)-2 is an anti-apoptotic gene, and it is a poor prognostic factor in various malignant tumors. However, the prognostic significance of bcl-2 expression in breast cancer remains controversial. We investigated the prognostic significance of bcl-2 according to cancer molecular subtype. Methods: We analyzed 411 patients with primary invasive breast cancer who underwent surgery at our institution between 1999 and 2001. The subtypes were classified as luminal (estrogen receptor [ER]+ and/or progesterone receptor [PR]+, irrespective of human epidermal factor receptor 2 [HER2]), triple-negative (ER-, PR-, and HER2-), or HER2 (ER- ,PR-, and HER2+). Results: A total of 236 (57.4%) cases were positive for bcl-2, and bcl-2 expression was significantly associated with earlier stage, lower grade, expression of hormone receptor positivity, and HER2 negativity. No difference in disease-free survival (DFS) was observed based on bcl-2 expression. However, the prognostic significance of bcl-2 varied with subtype; bcl-2 was not a prognosticator in patients with the luminal and HER2 subtypes. However, patients with bcl-2(+) tumors of the triple-negative subtype showed significantly worse DFS than those with bcl-2(-) tumors (p=0.048). In a multivariate analysis, bcl-2 expression remained a significant predictor of recurrence in patients with the triple-negative subtype (hazard ratio, 3.26; 95% confidence interval, 1.40-7.59; p=0.006). Conclusion: The prognostic significance of bcl-2 varied with molecular subtype; bcl-2 expression was a poor prognosticator in patients with the triple-negative subtype, but not in those with the luminal and HER2 subtypes.