Risk of endometrial cancer among breast cancer survivors in Japan: a matched cohort study.

Background: Breast cancer (BC) survivors may have an increased risk of endometrial cancer due to shared risk factors and tamoxifen use. However, the risk among women in Japan and that for each endocrine therapy regimen remains unknown when comparing BC survivors to women without BC.

Methods: We conducted a matched-cohort study using the JMDC claims database, covering company employees and their family members in Japan. Between January 2005 and December 2019, women aged 18-74 years with BC were matched to women without BC in a 1:4 ratio by age and database entry timing. Endometrial cancer risk was compared using stratified Cox regression. In addition, starting the follow-up at one year after matching, we assessed risk by endocrine treatment (tamoxifen, aromatase inhibitor [AI], and no endocrine therapy) using unstratified Cox regression.

Results: Among 23,729 BC survivors and 95,659 matched women (median age, 49.5 years), there were 56 vs 40 endometrial cancer cases (0.73 vs 0.13 cases/1,000 person-years, respectively), with adjusted hazard ratios of 7.71 (95% confidence interval 4.56-13.0). In the analysis by endocrine treatment, tamoxifen (n = 9,183; median 46.3 years), AI (n = 4,582; 58.1 years), and no endocrine therapy (n = 5,763; 49.4 years) cases were 26, 5, and 10 (0.92, 0.43, and 0.61 cases/1,000 person-years, respectively), and the adjusted hazard ratios were 5.67 (3.20-10.0), 2.17 (0.79-5.95), and 3.56 (1.66-7.65), respectively, compared to women without BC.

Conclusions: BC survivors in Japan had an increased risk of endometrial cancer compared to women without BC. The risk was higher in women prescribed tamoxifen and those with no endocrine therapy.