Tamoxifen use linked to risk of uterine diseases in premenopausal breast cancer patients

Premenopausal breast cancer patients who are receiving tamoxifen as adjuvant hormone therapy appear to be at increased risk of uterine diseases, including endometrial cancer, according to a target trial emulation study from Taiwan.

Researchers used the National Health Insurance claims data linked to the cancer registry. They identified women aged 20–50 years who were diagnosed with estrogen receptor–positive breast cancer and had undergone mastectomy or lumpectomy. Exclusion criteria included a history of hysterectomy, neoadjuvant therapy, and diagnosis of postmenopausal status and uterine diseases.

Tamoxifen exposure in the study was defined as receipt of the drug as adjuvant hormone treatment within 1 year after surgery.

The analysis included 23,062 tamoxifen users (mean age 43.1 years) and 3,000 nonusers (mean age 42.4 years). Compared with nonuser, tamoxifen users had slightly higher BMI and were more likely to receive axillary lymph node surgery and to have more advanced pathologic stages, smaller tumours, ductal histology, and invasive margins. Moreover, tamoxifen users were more likely to have progesterone receptor–negative and human epidermal growth factor receptor 2–negative tumours.

Over a median follow-up of 4.5 years, uterine diseases occurred in 3,889 tamoxifen users and 109 nonusers. Of these, 106 and five had endometrial cancer, respectively.

In the intention-to-treat analysis, tamoxifen use was associated with an increased hazard of endometrial polyps (hazard ratio [HR], 4.15, 95 percent confidence interval [CI], 2.65–6.50), endometrial hyperplasia (HR, 5.42, 95 percent CI, 4.09–7.18), and endometrial cancer (HR, 2.41, 95 percent CI, 0.86–6.72) compared with nonuse.

Results were consistent in the per-protocol analysis, with elevated risks of endometrial polyps (HR, 4.75, 95 percent CI, 2.55–8.86), endometrial hyperplasia (HR, 8.37, 95 percent CI, 5.24–13.35), and endometrial cancer (HR, 4.20, 95 percent CI, 1.20–14.63) observed with tamoxifen use vs nonuse.

The risk of all uterine diseases further increased with longer duration of tamoxifen use.