Evolution in the risk of adverse events of adjuvant endocrine therapy in postmenopausal women with early-stage breast cancer

Abstract

Abstract Background Adjuvant endocrine therapy is a gold standard in early-stage, hormone receptor-positive breast cancer. In postmenopausal women aromatase inhibitors (AIs) are associated with improved outcome compared to tamoxifen monotherapy. Differences in the toxicity profiles of these drugs are described, however, little is known about whether the risk of adverse events changes over time. Methods Sequential reports of large, randomized, adjuvant endocrine therapy trials comparing AIs to tamoxifen were reviewed. Data on pre-specified adverse events were extracted including cardiovascular events, bone fractures, cerebrovascular disease, endometrial cancer, other secondary malignancies, venous thrombosis and death without recurrence. Odds ratios (ORs) were calculated for serial publications over follow-up. The change in the ORs for adverse events over time was evaluated using weighted linear regression. Results Analysis included 22 reports of 7 trials reporting outcomes between 25.8 and 120 months of follow-up. Over time, the differences in toxicity profiles between AIs and tamoxifen did not change significantly (Table). Compared to tamoxifen, longer duration of AI use was associated with a non-significant reduction in the OR for bone fracture and a non-significant increase in the OR for thromboembolic events. Table . 204P Event β p Fractures -0.431 0.084 Cardiovascular events -0.189 0.557 Cerebrovascular disease 0.088 0.823 Thromboembolic events 0.389 0.169 Secondary cancer 0.227 0.365 Endometrial cancer -0.104 0.671 Death without recurrence 0.043 0.852 Conclusions Differences in toxicity profiles between adjuvant AIs and tamoxifen do not change significantly over time. Drug-specific toxicity (e.g. bone fractures with AI and thromboembolism with tamoxifen) may fall over time and after discontinuation of treatment. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure E. Amir: Speaker Bureau / Expert testimony: Genentech/Roche; Advisory / Consultancy: Apobiologix; Advisory / Consultancy: Agendia; Advisory / Consultancy: Myriad Genetics. H. Goldvaser: Honoraria (self): Roche. R. Yerushalmi: Honoraria (self): Roche; Honoraria (self): Medison; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Teva. All other authors have declared no conflicts of interest.