Impact of endocrine therapy regimens for early-stage ER+/HER2- breast cancer on contralateral breast cancer risk

Endocrine therapy for breast cancer may reduce the risk of contralateral breast cancer (CBC). However, there are no published estimates quantifying the lifetime outcomes by age at primary diagnosis, regimen, or duration. Here, we adapted an established Cancer Intervention and Surveillance Network (CISNET) model to simulate life histories of multiple US female birth-cohorts diagnosed with stage 0-III ER+/HER2- breast cancer receiving different durations (none, 2.5, 5, 10 years) of two endocrine therapy regimens (aromatase inhibitors or tamoxifen; including ovarian-function suppression for premenopausal women). As expected, greater duration of endocrine therapy led to more avoided CBC cases, as did aromatase inhibitors over tamoxifen, but the numbers varied greatly by the age of diagnosis. The maximum number of CBC were avoided using 10-year aromatase inhibitor regimens (6.0 vs. 11.2 for no adjuvant therapy, per 100 women with ER+/HER2- breast cancer). For the 5-year aromatase inhibitors therapy, women <45 years had the largest reduction in CBC cases (5.0/100), which dropped to 2.7/100 for women at 75+ years. Quantification of the lifetime risk of CBC for specific endocrine therapy types and duration is helpful for weighing therapeutic options. The risk of breast cancer death has a larger weight, but inclusion of the risk of CBC increases the separation between different therapy options.