Exogenous hormones and patients at increased risk for breast cancer

Exogenous hormones and patients at increased risk for breast cancer: © NaMong Productions - stock.adobe.com

“The absolute risks associated with exogenous hormones are low, even in very high-risk patients, and the benefits are often substantial,” according to a presentation by Holly J. Pederson, MD, at The Menopause Society 2023 Annual Meeting.

There is a prevalent concern that exogenous hormone exposure increases breast cancer risk in women, as estrogen promotes mammary cancer development in animal studies. Serum estradiol levels have also been significantly associated with estrogen receptor-positive breast cancer.

Breast cancer may also be impacted by the timing of exposure. A protective differentiation of breast tissue occurs during the first full-term pregnancy. This lecture looked at combined oral contraceptives in BRCA carriers and other high-risk patients, and HT in postmenopausal gene carriers as well as other high-risk women.

An increased risk of endometrial cancer has also been seen in BRCA1 and BRCA2 carriers, however, ovarian and endometrial cancer risk decreases from the use of combined hormonal contraceptives, both in gene positive and gene negative patients, with benefits lasting 15 years.

Why would this matter if a woman who carries a BRCA mutation is going to have her ovaries out between ages 35 and 45 years? Unfortunately, most women do not adhere to these guidelines. A retrospective review found only 17% of women with a PV/LPV in BRCA1 received RRSO by the recommended age. Additionally, oophorectomy has been reported in approximately 65% of patients with BRCA1.

Combined oral contraceptive use has also been consistently associated with a 50% reduction in ovarian cancer risk in BRCA1 and BRCA2 carriers. Additionally, multiple studies have found no increased risk of breast cancer from combined oral contraceptive use, even before the first full-term pregnancy. However, these studies are small and with limited follow-up, making shared decision-making between patients and providers vital.

An association between oral contraceptive use and increased breast cancer risk has also not been found among women with a family history of breast cancer. The risk of breast cancer from the use of combined oral contraceptives is very low in average-risk women, measured as 1 extra case per 7,690 users per year. Similar results have also been observed in IUD users.

Early surgical menopause has been shown to be associated with accelerated osteoporosis and cardiovascular disease. Even in BRCA carriers, Hormone Therapy (HT) is recommended by the National Comprehensive Cancer Center until the age of natural menopause and has not been associated with an increase in breast cancer risk. In fact, BRCA2 carriers who have early surgical menopause benefit from a 50-55% lowered risk of breast cancer, that is unaffected by hormone use.

Though breast cancer risk is the primary concern of many women, heart disease is more common and more threatening. We cannot focus on breast cancer risk without considering the whole patient. In midlife women, menopausal hormone therapy reduces hot flashes and night sweats, and prevents bone loss and fracture, but its effects on cardiovascular disease were poorly understood. In 2020, the American Heart Association published a Scientific Statement regarding menopause and cardiovascular disease. Postmenopausal HT is associated with a 30% reduction in all cause mortality when HT is initiated in young menopausal women. This makes the benefits of hormone therapy outweigh the risks for most women aged under 60 years (in the absence of contraindications.)

Individualize therapy and recommendations based on current data and patient preference. Consider a personal or family history of breast cancer in the discussion, but also a personal or family history of early cardiovascular disease.

Reference

Pederson HJ. Exogenous hormones and patients at increased risk for breast cancer. Presented at: The Menopause Society 2023 Annual Meeting, Philadelphia, Pennsylvania.