Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients

Abstract

Background: The benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor-positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain. Methods: All Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression. Results: After an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend =. 002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends. Conclusions: These results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.