Optimal adjuvant endocrine treatment of ER+/HER2+ breast cancer patients by age at diagnosis: A population-based cohort study. (February 2018)

• Record Type: Journal Article
• Authors: Dackus, G.M.H.E.; Jóźwiak, K.; Sonke, G.S.; van der Wall, E.; van Diest, P.J.; Hauptmann, M.; Siesling, S.; Linn, S.C.
• Is Part Of: European journal of cancer. Volume 90(2018)
• Page Start: 92
• Page End: 101
• Publication Date: 2018-02
• Subjects: Breast cancer -- ER -- HER2 -- Endocrine treatment -- Survival analysis -- Time-dependent analysis; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.11.010
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Prior randomised controlled trials on adjuvant hormonal therapy included HER2any patients; however, a differential effect of aromatase inhibitors (AIs) versus tamoxifen (TAM) may have been missed in ER+/HER2+ patients that comprise 7–15% of all breast cancer patients. In addition, a woman's hormonal microenvironment may influence sensitivity to TAM and AIs in the adjuvant setting, which changes during menopausal transition, a process that takes years. We studied the efficacy of AIs versus TAM in ER+/HER2+ breast cancer patients grouped by age at diagnosis as a proxy for menopausal status using treatment and outcome data from the nationwide population-based Netherlands Cancer Registry (NCR). Patients and methods: All women diagnosed between 2005 and 2007 with endocrine-treated, Tany Nany M0, ER+/HER2+ breast cancer were identified through the NCR ( n = 1155). Patients were divided by age at diagnosis: premenopausal (≤45 years; n = 326), perimenopausal (4555 years; n = 525). A time-dependent variable, indicating whether AI or TAM was received for >50% of endocrine treatment duration, was applied to subdivide groups by predominant treatment received. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier survival estimation and Cox regression. Hazard ratios (HRs) were adjusted for chemotherapy, trastuzumab, age at diagnosis, N-status, grade, pT-stage and ovarian ablation. Results: During follow-up, 237 recurrences and 182 deaths occurred. Perimenopausal women derived significant RFS and OS benefit from AI compared with TAM, HR 0.47 (95% CI 0.25–0.91; P = 0.03) and HR 0.37 (95% CI 0.18–0.79; P = 0.01), respectively, whereas premenopausal women derived no benefit from AI compared with TAM. Treatment effects differed significantly between these age groups (interaction P = 0.03 and P = 0.02, respectively). Among postmenopausal women a small but non-significant AI benefit was observed. Conclusion: AI treatment, preferably without any TAM treatment, was associated with the best RFS and OS outcome in ER+/HER2+ perimenopausal breast cancer patients. Highlights: We studied all ER+/HER2+ Dutch breast cancer patients diagnosed between 2005 and 2007. Aromatase inhibitors (AIs) and tamoxifen (TAM) were compared in a time-dependent way. AIs not TAM significantly improve recurrence-free survival (RFS) and overall survival (OS) in perimenopausal women (45–55 years at diagnosis). 5-year RFS benefit for AI compared with TAM (90% vs. 78%; adjusted HR 0.47; P = 0.026). 5-year OS benefit for AI compared with TAM (96% vs. 87%; adjusted HR 0.37; P = 0.010).