Aromatase Inhibitors and the Risk of Colorectal Cancer in Post-Menopausal Women with Breast Cancer

Abstract

Background

A large trial of post-menopausal women with breast cancer reported an imbalance in colorectal cancer events with aromatase inhibitors (AIs), compared with tamoxifen in the adjuvant setting. This unexpected signal was observed within 3 years of randomization. To date, no observational studies have examined this important safety question in the natural setting of clinical practice. Thus, the objective of this study was to determine whether AIs, when compared with tamoxifen, are associated with increased risk of colorectal cancer in post-menopausal women with breast cancer.

Patients and Methods

Using the United Kingdom Clinical Practice Research Datalink, we identified women, at least 55 years of age, with breast cancer newly-treated with either AIs or tamoxifen between January 1, 1996 and September 31, 2015, with follow-up until September 31, 2016. High-dimensional propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident colorectal cancer associated with AIs when compared with tamoxifen overall, by cumulative duration of use, and time since initiation. All exposures were lagged by one year for latency considerations.

Results

A total of 9701 and 8893 patients initiated AIs and tamoxifen as first-line hormonal therapy (median follow-up of 2.4 and 2.9 years, respectively). Compared with tamoxifen, AIs were not associated with an increased risk of colorectal cancer (incidence rates of 150 per 100,000 person-years in both groups; adjusted HR: 0.90, 95% CI: 0.53-1.52). Similarly, there was no evidence of an association with cumulative duration of use (p-heterogeneity=0.54), and time since initiation (p-heterogeneity=0.66).

Conclusions

In this first population-based study, the use of AIs was not associated with an increased risk of colorectal cancer. These findings should provide reassurance to the concerned stakeholders.