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Patients with a history of infertility were at a modestly higher risk of developing breast cancer after menopause, according to a prospective study.

Women who had fertility issues in the past had a 13% increased risk of postmenopausal breast cancer (HR 1.13, 95% CI 1.00-1.28), reported Leslie Farland, ScD, MSc, of the University of Arizona in Tucson.

However, there was no association between infertility history and risk of breast cancer overall (HR 1.06, 95% CI 0.98-1.14) or premenopausal breast cancer (HR 1.06, 95% CI 0.95-1.19), Farland said during a virtual presentation at the American Society for Reproductive Medicine annual meeting.

The association between infertility history and postmenopausal breast cancer was strongest among those who experienced infertility at a younger age (ages ≤25: HR 1.17, 95% CI 0.98-1.39 vs >30: HR 0.98, 95% CI 0.78-1.23), and those who had primary infertility (HR 1.25, 95% CI 1.08-1.43) compared with secondary infertility (HR 0.89, 95% CI 0.72-1.09).

"Prior research on the association between infertility and risk of breast cancer has yielded inconsistent results," Farland noted. Studies of infertility and breast cancer risk are complex, she added, as many established risk factors for breast cancer, such as nulliparity and later age at first birth, are also associated with fertility issues.

In a mediation analysis, the researchers found that lower total parity and age at first birth accounted for more than 50% of the association between infertility and postmenopausal breast cancer.

"We observed no meaningful differences in breast cancer risk by specific infertility diagnoses or by hormone receptor status of the breast cancer tumors," they wrote.

In this study, Farland and team analyzed data from the Nurses' Health Study II, a prospective cohort of more than 115,000 registered nurses. Study participants were recruited when they were 25 to 42 years old, and were followed for 26 years for the incidence of breast cancer.

Over follow-up, 26,213 women reported infertility, and about 3,200 women were newly diagnosed with invasive breast cancer, 1,173 of whom were postmenopausal.

Participants self-reported their experience with infertility, which was defined as an attempt to conceive for at least 1 year without success. The researchers compared the incidence of breast cancer among those with and without a history of infertility.

Farland and colleagues adjusted their analyses for potential confounders, including breast cancer family history, race, body mass index, age at menarche, height, oral contraceptive use before age 18, history of benign breast disease, physical activity, alcohol consumption, recent mammogram, and hormone therapy.

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