Differential fracture risk in breast cancer patients based on endocrine therapy and age: a nationwide cohort study

Concerns about the risk of osteoporosis and osteoporotic fractures following endocrine therapy have increased with increase in breast cancer survivors. This study aimed to evaluate the incidence of fractures by site between tamoxifen and aromatase inhibitor (AI) users and non-users at premenopausal and postmenopausal ages.

This retrospective cohort study used data from the Korea Central Cancer Registry and the Korean National Health Insurance Service. We analyzed 63,021 newly diagnosed breast cancer patients between 2008 and 2016. The risk of fractures was analyzed according to post-surgical endocrine therapy using the multivariable Cox proportional hazard model.

Herein, 69.1% of the patients received endocrine therapy. The incidence rates of osteoporotic fractures per 1,000 person-years were 7.4 overall, 3.5 in those under 50, and 12.6 in those over 50. After adjusting for confounders, the tamoxifen group showed protection against any fractures in patients over 50 (HR = 0.75, 95% CI 0.62-0.89, p < 0.001) but not in those under 50. The AI ​​group was associated with a significant increase in fractures in those under 50 (HR = 1.54, 95% CI 1.07-2.93, p = 0.019) but not in those over 50.

Among breast cancer patients aged over 50 years, AI use was not associated with increased risk of compared to non-users. Tamoxifen use was linked to reduced risk of fracture, but not in patients under 50. Considering the relatively young age of breast cancer diagnosis in Korea, long-term follow-up studies are warranted. After adjusting for confounders including age, among breast cancer patients aged over 50 years, AI use was not associated with increased risk of fracture compared to non-users. Tamoxifen use was linked to reduced risk of fracture, but not in patients under 50.