Premenopausal women with breast cancer who received tamoxifen had a significantly increased risk for
polyps, carcinoma, endometrial hyperplasia, and other uterine cancers compared with premenopausal
women with breast cancer not using adjuvant hormone therapy, according to a study published in
JAMA Network Open.

The correlation of tamoxifen use with the risk for uterine diseases, such as endometrial
cancer, in premenopausal women with breast cancer remains controversial, the study authors wrote. However,
they pointed out that many studies have reported an increased risk for uterine disease among postmenopausal
users of tamoxifen.

Risk for Endometrial Cancer Higher Than in Control Group

To investigate the link between tamoxifen use and the risk for endometrial cancer and other uterine
diseases in premenopausal women with breast cancer, Ki-Jin Ryu, MD, and colleagues conducted an 18-year,
population-based, retrospective, longitudinal cohort study of 78,320 participants. Participants included
premenopausal women aged 20-50 with breast cancer diagnoses between January 2003 and December 2018.

Using insurance claim codes, researchers identified the rate of uterine diseases, including endometrial cancer,
hyperplasia, polyps, and other uterine cancers. The rate of uterine diseases per 1,000 person-years was
compared between women receiving tamoxifen and those not treated with adjuvant hormone therapy. To
determine the risk for each uterine disease, multivariable Cox proportional hazard regression analysis
was performed.

Awareness of Risks for Uterine Disease Is Key for Breast Cancer Survivors

Nearly half (44.2%) of participants were categorized into the tamoxifen group and 55.8% were included
into the control group. Among tamoxifen users, during the mean (SD) follow-up duration of 6.13 (4.15)
years, the rate of newly diagnosed endometrial polyps was 20.13 cases per 1,000 person-years; endometrial hyperplasia,13.49 cases per 1,000
person-years; endometrial cancer, 2.01 cases per 1,000 person-years; and other uterine cancers, 0.45
cases per 1,000 person-years. In the tamoxifen group, the risk for endometrial cancer was higher than in
the control group (HR, 3.77; 95% CI, 3.04-4.66) after adjusting for age, BMI, diabetes history,
dyslipidemia, hypertension, gonadotropin-releasing hormone agonist treatment, polycystic ovary syndrome,
and trastuzumab treatment.

“These findings suggest that awareness about the absolute risks for uterine diseases with long-term follow-up
is essential for the daily management of survivors of premenopausal breast cancer receiving tamoxifen and
that the risk for uterine diseases in tamoxifen users, specifically in premenopausal women, should be considered,”
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