Aromatase inhibitors have replaced tamoxifen as the mainstay treatment for breast cancer in post-menopausal women with breast cancer. However, safety results from a randomized controlled trial indicate that these drugs may be associated with colorectal cancer. To date, the association between aromatase inhibitors and colorectal cancer has not been examined in a real world setting. Thus, the aim of this study is to assess whether post-menopausal women diagnosed with breast cancer who are treated with aromatase inhibitors are at an increased risk of colorectal cancer in comparison to patients who are treated with tamoxifen.
A long-term follow-up of a randomized controlled trial (RCT) has indicated that AIs may increase the risk of colorectal cancer in comparison with tamoxifen. To date, this is only RCT that has reported on the incidence of colorectal between aromatase inhibitors and tamoxifen in post-menopausal women with breast cancer. Further, no observational studies have examined this association in clinical practice. Thus, the objective of this study is to use the Clinical Practice Research Datalink to assess whether the use of aromatase inhibitors, when compared with tamoxifen, is associated with an increased risk of colorectal cancer in a cohort of approximately 26,000 patients newly-diagnosed with breast cancer. The use of aromatase inhibitors and tamoxifen will be treated as a time-varying variable, with exposures lagged by one year for latency considerations and to minimize reverse causality. Time-dependent Cox proportional hazards model will be used to estimate adjusted hazard ratios (with 95% confidence intervals) of incident colorectal cancer associated with use of AIs when compared with tamoxifen use. This study will address an important safety question in an older population already at increased risk of colorectal cancer.
Patients will be considered exposed to AIs or tamoxifen starting one year after the date of the first prescription until the end of follow-up. Lagging exposure by one year will be necessary given the possible diagnostic delays associated with colorectal cancer, to impose a minimum time period between exposure and the incidence of the colorectal cancer (latency), and minimize biases related to reverse causality (a situation where exposure might be initiated or terminated at early signs or symptoms of the outcome).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Alan Barkun - Collaborator - McGill University
Farzin Khosrow-Khavar - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Nathaniel Bouganim - Collaborator - McGill University