Tamoxifen treatment for breast cancer may increase endometrial disease, cancer risks

Tamoxifen use in the treatment of breast cancer was associated with greater risks for endometrial cancer, hyperplasia and polyps, as well as other uterine cancers among premenopausal women in Korea, according to study data.

“Although premenopausal women with breast cancer are usually treated with tamoxifen as first-line adjuvant hormone therapy, it remains unclear whether the use of tamoxifen in premenopausal women is associated with an increased risk of several uterine diseases, including endometrial cancer,” Ki-Jin Ryu, MD, PhD, a medical professional at Korea University Anam Hospital in Seoul, South Korea, and colleagues wrote. “Existing guidelines do not warn of the potential risk of gynecologic diseases with tamoxifen use, nor do they recommend routine screening for uterine diseases in premenopausal women receiving tamoxifen.”

Data collection

Ryu and colleagues conducted a retrospective longitudinal cohort study using data from the Korean National Health Insurance Service (NHIS), which includes records on hospital admissions and outpatients, medical treatment claims, results of health examinations and medical care institution information.

The researchers evaluated data from premenopausal women with a primary diagnosis of breast cancer in two or more instances from 2003 to 2018. They created two groups for analyses: the tamoxifen group, which received tamoxifen as the only adjuvant hormone treatment, and the control group, which did not receive any adjuvant hormone therapy. The tamoxifen group was further divided into women using tamoxifen for 5 years or less and women using tamoxifen for more than 5 years.

Overall, 34,637 (44.2%) women were treated with tamoxifen and 43,683 (55.8%) were not. The mean age among the total cohort was 42.1 years.

Risks associated with tamoxifen

In the tamoxifen group, there were 2,882 incidences of endometrial polyps, 1,911 incidences of endometrial hyperplasia, 307 incidences of endometrial cancer and 71 incidences of other uterine cancers. In the control group, there were 1,426 incidences of endometrial polyps, 493 incidences of endometrial hyperplasia, 119 incidences of endometrial cancer and 32 incidences of other uterine cancers.

Incidence of all diseases were more common in the tamoxifen group vs. the control group. Specifically, the tamoxifen group had more cases of endometrial polyps (20.13 vs. 5.5 cases per 1,000 person-years), more cases of endometrial hyperplasia (13.49 vs. 2.06 cases per 1,000 person-years), more cases of endometrial cancer (2.01 vs. 0.45 cases per 1,000 person-years) and more cases of other uterine cancers (0.45 vs. 0.16 cases per 1,000 person-years) compared with the control group.

Adjusted analyses revealed that the risk for endometrial cancer was almost four times higher in the tamoxifen group compared with the control group (HR = 3.77; 95% CI, 3.04-4.66). Tamoxifen use was also associated with a greater risk for endometrial polyps (HR = 3.9; 95% CI, 3.65-4.16), endometrial hyperplasia (HR = 5.56; 95% CI, 5.06-6.12), other uterine cancers (HR = 2.27; 95% CI, 1.54-3.33) and any of these diseases (HR = 4.2; 95% CI, 3.98-4.44).

There were no differences in risk for any outcomes between women in the tamoxifen group based on duration of use.

“Our findings clearly indicate that clinicians should consider the risks of endometrial cancer and other uterine malignant neoplasms among tamoxifen users, regardless of menopausal status,” Ryu and colleagues wrote. “Furthermore, the median age at which East Asian women receive a breast cancer diagnosis is approximately 10 years lower than that of Western women. This makes it particularly important for clinicians to be aware of the risks of various uterine diseases in young premenopausal breast cancer survivors receiving adjuvant hormone therapies.”