Hormone Therapy Use May Impact Early-Onset Breast Cancer Risk

Common hormone therapies used manage symptoms related to menopause or following hysterectomy may impact the risk of breast cancer in younger women, a new study published in the Lancet Oncology found.1

Women who received unopposed estrogen hormone therapy (E-HT) were less likely to develop breast cancer than those who did not use hormone therapy, but those treated with estrogen plus progestin hormone therapy (EP-HT) were at a higher risk of the disease than those who did not use hormone therapy.

Early-onset breast cancer found to be associated with certain hormone therapy usage in younger women. | Image Credit: Chinnapong - stock.adobe.com

Early-onset breast cancer can occur in women aged 18 to 45, and while it is less common, the risk is not zero. While the rate of occurrence is low (11%), it is still the most common cancer among women ages 15 to 39.2

Hormone therapy is commonly used to manage symptoms associated with surgical or natural menopause, as well as other hormone-related conditions.1 However, due to the relatively low incidence of breast cancer in younger populations, research often excludes data on younger women. Previous studies have established a link between EP-HT and an increased risk of breast cancer in postmenopausal women, the authors noted.

"Hormone therapy can greatly improve the quality of life for women experiencing severe menopausal symptoms or those who have had surgeries that affect their hormone levels,” lead author Katie O’Brien, PhD, of the National Institute of Health’s National Institute of Environmental Health Sciences (NIEHS), said in a statement.3 “Our study provides greater understanding of the risks associated with different types of hormone therapy, which we hope will help patients and their doctors develop more informed treatment plans.”

The study included pooled data from 547,751 women aged 16 to 54 years old across 13 cohorts, 2% (9482) of whom developed early-onset breast cancer before age 55.1 Among them, only 15% reported using hormone therapy. Of the 15%, 6% reported using EP-HT and 5% reported using E-HT, which were the 2 most common hormone therapies used by participants in the study.

The hazard ratio for EP-HT and young-onset breast cancer was 1.10 (95% CI, 0.98-1.24), with the risk increasing with long-term use, defined as greater than 2 years (HR, 1.18; 95% CI, 1.01-1.38). The risk of breast cancer was also higher among women without hysterectomy or bilateral oophorectomy who received EP-HT (HR, 1.15; 95% CI, 1.02-1.31).

However, women who used E-HT had a 14% reduction in breast cancer incidence compared with hormone therapy–naive women (HR, 0.86; 95% CI, 0.75-0.98). Those who initiated E-HT at a younger age or those who used it longer showed an even further reduced risk of breast cancer compared with those who never received hormone therapy.

“The inverse associations observed among women who started estrogen hormone therapy before age 45 years or who used it for longer durations lends further support to the idea that women who undergo menopause earlier, either naturally or surgically, might derive the most benefit from estrogen replacement,” the authors wrote.

Using hormone therapy of any type was not associated with young-onset breast cancer risk in the study (HR, 0.96; 95% CI, 0.88-1.04).

Study limitations included inconsistent hormone therapy dosage, as researchers were unable to collect type-specific data for reports of multiple types. Data substitutions used to account for the limitations of the study were also limited by the covariate information available. Data on hysterectomy and oophorectomy were also scarce in other studies.

Nevertheless, “the combined evidence supports that there might be health benefits, at least in terms of breast cancer risk, of using exogenous estrogen to replace depleted endogenous estrogen,” the authors stated.

"These findings underscore the need for personalized medical advice when considering hormone therapy,” Dale Sandler, PhD, NIEHS scientist and senior author, said in a statement.3 “Women and their health care providers should weigh the benefits of symptom relief against the potential risks associated with hormone therapy, especially EP-HT. For women with an intact uterus and ovaries, the increased risk of breast cancer with EP-HT should prompt careful deliberation.”

References

1. O’Brien KM, House MG, Goldberg M, et al. Hormone therapy use and young-onset breast cancer: A pooled analysis of prospective cohorts included in the premenopausal breast cancer collaborative group. The Lancet Oncology. 2025;26(7):911-923. doi:10.1016/s1470-2045(25)00211-6

2. Moriarty C. Too young to screen: Breast cancer in younger women. Yale Medicine. April 30, 2024. Accessed July 2, 2025. https://www.yalemedicine.org/news/breast-cancer-younger-women

3. Breast cancer risk in younger women may be influenced by hormone therapy. News release. National Institutes of Health. June 30, 2025. Accessed July 26, 2025. https://www.nih.gov/news-events/news-releases/breast-cancer-risk-younger-women-may-be-influenced-hormone-therapy