Tamoxifen Use and Risk of Uterine Diseases in Young Women With Breast Cancer

Tamoxifen use has been associated with an increased risk of endometrial cancer in women with breast cancer, but data on premenopausal women in Asia remain limited. We investigated the association between tamoxifen treatment and risk of developing uterine diseases in women of premenopausal age with breast cancer.

We conducted a retrospective cohort study using a target trial emulation framework. Women aged 20-50 years who were diagnosed with estrogen receptor-positive breast cancer and had undergone mastectomy or lumpectomy from 2010 to 2019 were identified with Taiwan's National Health Insurance claims data linked to the cancer registry. Those with a history of hysterectomy, neoadjuvant therapy, and diagnosis of postmenopausal status and uterine diseases were excluded. Tamoxifen use was defined as receipt tamoxifen treatment only as adjuvant hormone treatment within 1 year after surgery. Inverse probability of treatment weighting controlled baseline confounding between the tamoxifen treatment and nontreatment groups. Observational analogs of the intention-to-treat and per-protocol effects were estimated with pooled logistic regression models.

A total of 23,062 tamoxifen users and 3,000 nonusers were included. During the follow-up period, 3,889 users and 109 nonusers developed uterine diseases, including 106 and 5 cases of endometrial cancer, respectively. In the intention-to-treat analysis, the hazard ratio was 4.15 (95% CI, 2.65-6.50) for endometrial polyps, 5.42 (95% CI, 4.09-7.18) for endometrial hyperplasia, and 2.41 (95% CI, 0.86-6.72) for endometrial cancer. Corresponding estimates from the per-protocol analysis were 4.75 (95% CI, 2.55-8.86), 8.37 (95% CI, 5.24-13.35), and 4.20 (95% CI, 1.20-14.63), respectively. The risk of all uterine diseases increased with longer duration of tamoxifen use.

Among women of premenopausal age with breast cancer in Taiwan, tamoxifen as adjuvant hormone therapy was associated with increased risk of uterine diseases, including endometrial cancer. These findings highlight the importance of monitoring uterine diseases among tamoxifen users in this age range.