Prediction of Late Breast Cancer-Specific Mortality in Recurrence-Free Breast Cancer Survivors Treated for Five Years with Tamoxifen

Abstract

Purpose: The extension of endocrine therapy beyond 5 years for recurrence-free survivors of breast cancer improves survival; however, the issue on how to clinically identify appropriate candidates remains controversial. This study aimed to identify prognostic factors for breast-cancer-specific mortality in patients who have had 5 years of tamoxifen treatment and categorize subgroups based on the risk of death using combinations of these prognostic factors to assist in the clinical decision to perform further endocrine therapy.

Methods: In total, 3,158 patients with breast cancer were enrolled. Breast cancer-specific survival rates after 5 years of tamoxifen treatment were calculated, and associated prognostic factors were analyzed using a Cox proportional-hazards model.

Results: An age extreme at diagnosis (i.e., < 40 or ≥ 60 years), tumor size > 2 cm, and positive lymphovascular invasion were robust independent prognostic factors for late breast cancer-specific death in tamoxifen-treated patients (hazard ratio [HR] = 2.162, 1.739, and 1.993; p = 0.001, 0.047, and 0.011, respectively). Lymph node metastasis and progesterone receptor negativity had borderline significance in this regard (HR = 1.741 and 1.638, p = 0.099 and 0.061). The study patients were classified into four groups according to the number of prognostic indicators, i.e., low, intermediate, high, and extremely high risk. The additional 5- and 10-year cumulative risks of breast cancer-specific death were 0.8% and 1.5% in the low-risk group, 0.9% and 3.9% in the intermediate-risk group, 1.3% and 7.3% in the high-risk group, and 4.8% and 13.8% in the extremely high-risk group, respectively.

Conclusion: This new risk stratification system for late mortality in breast cancer can be used to identify the right candidates for extended endocrine therapy after 5 years of tamoxifen treatment.

Keywords: Breast neoplasms; Cancer survivors; Prognosis; Tamoxifen.

Figure 1. BCSS after 5 years of scheduled tamoxifen treatment by (A) age at diagnosis, age extreme vs. middle aged; (B) tumor size, > 2 vs. ≤ 2 cm; (C) nodal status, positive vs. negative; (D) tumor grade, grade 1 vs. grade 2/3; (E) LVI, positive vs. negative; (F) PR expression, positive vs. negative; (G) CT, yes vs. no; and (H) year of diagnosis, 1999–2003 vs. 2004–2008. (A-H) All factors were found to be significant predictors for BCSS by univariate survival analyses.

BCSS = breast cancer-specific survival; LVI = lymphovascular invasion; PR = progesterone receptor; CT = chemotherapy.

Figure 2. BCSS after 5 years of scheduled tamoxifen treatment in subgroups classified using the risk stratification system. The low, intermediate, high, and extremely high-risk groups had 0, 1, 2, and 3 or more predictors, respectively, among variables including age extreme at diagnosis, tumor size > 2 cm, positive LVI, LN metastasis, and PR negativity.

BCSS = breast cancer-specific survival; LVI = lymphovascular invasion; LN = lymph node; PR = progesterone.