Prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer

Abstract

We investigated the prognostic influences of BCL1 and BCL2 expression on disease-free survival in breast cancer patients. BCL1 and BCL2 expression statuses were assessed by immunohistochemistry using tissue microarrays from 393 breast cancer patients. The Kaplan-Meier estimator and log-rank test were used for survival analyses. The Cox proportional hazards model was used to calculate hazard ratio (HR) and the 95% confidence interval (CI) of survival analyses. BCL1 expression revealed no impact on survival. The high BCL2 group showed superior disease-free survival compared with the low BCL2 group (p = 0.002), especially regarding local recurrence-free survival (p = 0.045) and systemic recurrence-free survival (p = 0.002). BCL2 expression was a significant prognostic factor by univariable analysis (HR, 0.528; 95% CI, 0.353-0.790; p = 0.002) and by multivariable analysis (HR, 0.547; 95% CI, 0.362-0.826; p = 0.004). High BCL2 expression was associated with higher disease-free survival in the hormone receptor (HRc)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HRc(+)/HER2(-)) subtype only (p = 0.002). The high BCL2 group was associated with positive estrogen receptor (ER), positive progesterone receptor (PR), low histologic grade, and age ≤ 50 years. BCL1 expression had no prognostic impact, but BCL2 expression was a significant independent prognostic factor. High BCL2 expression was associated with higher disease-free survival, especially regarding local recurrence and systemic recurrence. The prognostic effect of BCL2 expression was effective only in the HRc(+)/HER2(-) subtype. Favorable clinicopathologic features and a strong association with the ER/PR status could partly explain the superior prognosis of the high BCL2 group. BCL2 expression could be utilized to assess the prognosis of breast cancer patients in clinical settings.

Figure 1

Disease-free survival curves according to BCL1 and BCL2 statuses. Disease-free survival according to BCL1 status (A) and BCL2 status (B).

Figure 2

Detailed disease-free survival curves according to BCL2 status. Local recurrence-free survival (A), regional recurrence-free survival (B), systemic recurrence-free survival (C), and contralateral breast cancer recurrence-free survival (D).

Figure 3

Subgroup analyses by Cox proportional hazards model according to BCL2 status regarding disease-free survival. Abbreviation: CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hazard ratio. ^a)HRs are the relative risks of the high BCL2 group with reference of the low BCL2 group by Cox proportional hazards model. ^b)In the forest plot, a HR value of less than 1 favors the high BCL2 group against the low BCL2 group. The red circles mean statistical significance and the blue squares mean no statistical significance. The green diamond means the result of total subjects.

Figure 3

Subgroup analyses by Cox proportional hazards model according to BCL2 status regarding disease-free survival. Abbreviation: CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR, hazard ratio. ^a)HRs are the relative risks of the high BCL2 group with reference of the low BCL2 group by Cox proportional hazards model. ^b)In the forest plot, a HR value of less than 1 favors the high BCL2 group against the low BCL2 group. The red circles mean statistical significance and the blue squares mean no statistical significance. The green diamond means the result of total subjects.

Figure 4

Disease-free survival curve according to BCL2 status in each breast cancer subtype. HRc(+)/HER2(−) (A), HRc(+)/HER2(+) (B), HRc(−)/HER2(+) (C), and HRc(−)/HER2(−) (D). Abbreviation: HER2, human epidermal growth factor receptor 2; HRc, hormone receptor; PS, proportion score.