Some Hormone Therapies Linked to Young-Onset Breast Cancer

 

• Hormone therapy may be used by young women to relieve symptoms from hormone-­related conditions, menopause, or gynecologic surgery.
• Use of estrogen hormone therapy was inversely associated with young-onset breast cancer.
• Long-term use of estrogen/progestin hormone therapy was positively associated with young-­onset breast cancer, as was use among women with an intact uterus and ovaries.

While use of estrogen hormone therapy was inversely associated with young-onset breast cancer, estrogen/progestin hormone therapy was linked to a higher incidence among certain subgroups, according to a pooled cohort analysis.

Among over 450,000 women ages 16 to 54, hormone therapy of any type was not associated with incident young-onset breast cancer (HR 0.96, 95% CI 0.88-1.04), but ever estrogen hormone therapy use had an inverse association (HR 0.86, 95% CI 0.75-0.98), reported Katie M. O'Brien, PhD, of the National Institute of Environmental Health Sciences, and colleagues in Lancet Oncologyopens in a new tab or window.

However, long-term use (>2 years) of estrogen/progestin hormone therapy was positively associated with young-­onset breast cancer (HR 1.18, 95% CI 1.01-1.38), as was use among women without hysterectomy or bilateral oophorectomy (HR 1.15, 95% CI 1.02-1.31).

Estrogen/progestin hormone therapy was more strongly associated with estrogen receptor-negative disease (HR 1.44, 95% CI 1.11-1.88) and triple-negative disease (HR 1.50, 95% CI 1.02-2.20) compared with other subtypes.

"Young women might use hormone therapy to relieve symptoms from hormone-­related conditions, menopause, or gynecological surgery, but the risks and benefits of doing so have not been thoroughly investigated," wrote O'Brien and colleagues. "Altogether, the results of this large-­scale investigation, in conjunction with mostly consistent results from previous studies of postmenopausal womenopens in a new tab or window, provide key information that might be useful for establishing clinical recommendations regarding hormone therapy use in young women."

In a press releaseopens in a new tab or window, co-author Dale Sandler, PhD, also of the National Institute of Environmental Health Sciences, noted that "these findings underscore the need for personalized medical advice when considering hormone therapy."

"Women and their healthcare providers should weigh the benefits of symptom relief against the potential risks associated with hormone therapy, especially EP-HT [estrogen/progestin hormone therapy]," he said. "For women with an intact uterus and ovaries, the increased risk of breast cancer with EP-HT should prompt careful deliberation."

In a commentary accompanying the studyopens in a new tab or window, Christelle Lévy, MD, of the Centre Francois Baclesse Centre for Cancer in Caen, France, wrote that a "one-size-fits-all strategy is probably not the best approach," considering young women eligible for hormone therapy often present with various clinical and biological profiles.

"Recommendations for young women should consider knowledge of the benefit-risk profile of hormonal therapy and the unanswered questions in this domain (such as biological and genomic features of cancer cells at a young age or the impact of endogenous and exogenous factors on the initiation and neoplastic progression), emphasizing the importance of prospective trials that are truly missing compared with the abundant literature available for postmenopausal women," she added.

For this study, O'Brien and colleagues pooled data from 459,476 women across prospective cohorts in North America, Europe, Asia, and Australia. Mean age was 42, 79% were white, 14% were Black, and 5% were Asian; 12% had undergone a hysterectomy, and 5% had undergone bilateral oophorectomy. Overall, 15% of the study participants reported using hormone therapy, with estrogen/progestin (6%) and unopposed estrogen (5%) being the most common types.

Of these women, 2% developed young-onset breast cancer (diagnosed before age 55; median follow-up 7.8 years). Women who developed young-­onset breast cancer during follow-­up were slightly younger at enrollment (mean 40.7 years) and less likely to be postmenopausal (14% vs 21% in the full pooled sample).

HR estimates for associations were largely similar across menopausal status, age, body mass index, race, geographical region, and birth year.

O'Brien and colleagues acknowledged that their study had limitations, including the fact that they were unable to adjust for alcohol use or physical activity, and they did not have any data on BRCA1/2 or other known breast cancer predisposition genes. Moreover, they noted that their results may not be generalizable to all groups, since the pooled sample was made up primarily of white women from North America.

Disclosures

The study was funded by the NIH Intramural Research Program.

The study authors had no disclosures.

Lévy had no disclosures.

Primary Source

Lancet Oncology

Source Reference: opens in a new tab or windowO'Brien KM, et al "Hormone therapy use and young-onset breast cancer: a pooled analysis of prospective cohorts included in the Premenopausal Breast Cancer Collaborative Group" Lancet Oncol 2025; DOI: 10.1016/S1470-2045(25)00211-6.

Secondary Source

Lancet Oncology

Source Reference: opens in a new tab or windowLévy C "Hormonal therapy for young-onset breast cancer: current understanding and lessons" Lancet Oncol 2025; DOI: 10.1016/S1470-2045(25)00268-2.

https://www.medpagetoday.com/hematologyoncology/breastcancer/116344