Hormone Therapy Confers Modest Breast Cancer Risk Even With Family History

"The risk of dying from breast cancer remains low, and our modelling shows only a quite modest added risk from taking hormone replacement therapies," according to study author Clare Turnbull, MD, PhD.

Although a risk model showed that family history and use of menopausal hormone therapy (MHT) correlated with an increased risk of breast cancer, a single year of MHT administration conferred a comparatively modest risk of disease incidence and mortality, according to findings from an epidemiological modelling study published in British Journal of General Practice.¹

Among average 50-year-old populations with unknown family history and no MHT use, the cumulative risk of developing breast cancer was 2.7% to 60 years, 6.2% to 70 years, and 9.8% to 80 years. These respective risk rates changed to 3.5%, 7.5%, and 11.0% with 5 years of combined-cyclical MHT and to 4.5%, 8.9%, and 12.4% with 10 years of MHT use.

For 50-year-old individuals and a strong family history—defined as having 2 first-degree relatives with a breast cancer diagnosis—the cumulative breast cancer risk without the use of MHT was 7.0% to 60 years, 14.2% to 70 years, and 19.6% to 80 years. At each time point, the rates were 9.1%, 17.2%, and 22.4% with 5 years of MHT and 11.3%, 20.1%, and 25.2% with 10 years of MHT. Among those with 5 and 10 years of combined MHT use, respectively, the investigators noted increases of 1.3% and 2.7% for absolute breast cancer risk in individuals with an average family history compared with increases of 3.0% and 5.9% in those with a strong family history.

The risk of breast cancer-related mortality in individuals with an average family history from 50 to 80 years of age was 1.7% with no MHT use, 1.8% with 5 years of MHT, and 2.0% with 10 years of MHT. Among those with a strong family history, these rates were 3.2%, 3.5%, and 3.8%, respectively.

“We know some women are concerned about taking hormone replacement therapies due to the increased risk of breast cancer. Our modelling may provide reassurance that taking these treatments only increases that risk quite modestly, even for those women already with an increased risk of breast cancer due a family history of disease,” senior study author Clare Turnbull, MD, PhD, a professor of Translational Cancer Genetics at The Institute of Cancer Research, London, and a consultant in Clinical Cancer Genetics at The Royal Marsden NHS Foundation Trust, stated in a press release on these findings.² “The risk of dying from breast cancer remains low, and our modelling shows only a quite modest added risk from taking hormone replacement therapies.”

Investigators aimed to quantify the risks related to the use of MHT in individuals with different breast cancer family histories of developing and dying due to breast cancer. Use of the validated BOADICEA breast cancer prediction model helped estimate the baseline risks of breast cancer in individuals without MHT use. Additionally, investigators collected data on relative breast cancer risks associated with current or prior combined-all, combined-cyclical, combined-continuous, and estrogen-only MHT from the Collaborative Group on Hormonal Factors in Breast Cancer.

The study included female 50-year-old consultands who fit into one of 4 categories. Individuals who were average had an unknown family history related to cancer, those with a modest history had 1 first-degree relative with a breast cancer diagnosis at 60 years of age, those with an intermediate history had 1 first-degree relative with breast cancer at 40 years of age, and those with a strong family history had 2 first-degree relatives with disease at the age of 50.

Additional findings showed that estrogen-only MHT conferred a modest relative risk of breast cancer vs combined MHT. Among 50-year-old individuals with a strong family history, the breast cancer risk to 70 years was 14.2% with no MHT vs 15.8% and 16.6% with 5 and 10 years of estrogen-only MHT, respectively. These rates were 17.2% with 5 years and 20.1% with 10 years of combined-cyclical MHT.

References

1. Huntley C, Torr B, Kavanaugh G, et al. Breast cancer risk assessment for prescription of menopausal hormone therapy in women with a family history of breast cancer: an epidemiological modelling study. Br J Gen Pract. 2024;74(746):e610-e618. doi:10.3399/BJGP.2023.0327.
2. Breast cancer risk model provides reassuring data for those with family history of disease after short-term HRT use. News release. The Institute of Cancer Research. January 31, 2025. Accessed February 4, 2025. https://tinyurl.com/ypkh9m3t