Higher endometrial cancer, hyperplasia rates with conjugated estrogens/bazedoxifene

Key takeaways:

• Conjugated estrogen/bazedoxifene users had higher endometrial cancer and endometrial hyperplasia rates vs. estrogen/progestin users.
• Conjugated estrogen/bazedoxifene users had lower breast cancer incidence.

In the first years of use, women prescribed conjugated estrogens/bazedoxifene vs. estrogen/progestin for menopausal symptoms may have higher rates of endometrial cancer and endometrial hyperplasia but lower breast cancer rates.

“Bazedoxifene is a [selective estrogen receptor modulator] that was developed as an estrogen antagonist in breast and endometrial tissue. Combined with conjugated estrogens, it is the first approved hormone therapy to pair estrogen with a [selective estrogen receptor modulator] for the treatment of the vasomotor symptoms associated with menopause,” Sarah R. Hoffman, MS, MPH, PhD, research scientist at Carelon Research, Safety and Epidemiology in Wilmington, Delaware, and colleagues wrote. “No studies have compared the rates of endometrial outcomes and breast cancer between [conjugated estrogens/bazedoxifene] and estrogen-progestin therapy users.”

Hoffman and colleagues conducted a real-world, multi-database cohort study with data from 10,596 women who were new conjugated estrogens/bazedoxifene users and 33,818 propensity score-matched new estrogen/progestin combination users from five U.S. health care claims databases from May 2014 to August 2019. Endometrial cancer, endometrial hyperplasia, breast cancer and eight additional cancer and cardiovascular outcomes incidences were obtained using claims-based algorithms.

Overall, 39 endometrial cancer cases occurred during 82,458 person-years of follow-up, and 28 endometrial hyperplasia cases occurred during 38,770 person-years of follow-up.

Researchers observed higher endometrial cancer incidence rates (5.2 vs. 3.6 per 10,000 person-years; RR = 1.5; 95% CI, 0.79-2.88) and endometrial hyperplasia incidence rates (11 vs. 10.6 per 10,000 person-years; RR = 1.69; 95% CI, 0.51-5.61) among women using conjugated estrogens/bazedoxifene compared with women using estrogen/progestin.

A total of 286 breast cancer cases occurred during 82,047 person-years of follow-up. Women using conjugated estrogens/bazedoxifene had lower breast cancer incidence compared with women using estrogen/progestin (27.2 vs. 36.3 per 10,000 person-years; RR = 0.79; 95% CI, 0.58-1.05).

In addition, researchers noted that thyroid cancer (RR = 1.5; 95% CI, 0.8-2.9), gastrointestinal cancer (RR = 0.8; 95% CI, 0.4-1.5) and stroke (RR = 1.2; 95% CI, 0.7-2.1) all had similar rates to endometrial cancer for women using conjugated estrogens/bazedoxifene.

“The results of this multi-database study suggest that users of [conjugated estrogens/bazedoxifene] might experience slightly higher rates of endometrial cancer and endometrial hyperplasia and a lower rate of breast cancer than estrogen/progestin users, providing another option for women considering hormone therapy for vasomotor symptoms of menopause,” the researchers wrote.