Hormone therapy use and young-onset breast cancer: a pooled analysis of prospective cohorts included in the Premenopausal Breast Cancer Collaborative Group - 01/07/25

Doi : 10.1016/S1470-2045(25)00211-6

Katie M O’Brien, PhD ^a,⁎ , Melissa G House, MS ^b, Mandy Goldberg, PhD ^a, Michael E Jones, PhD ^c, Clarice R Weinberg, PhD ^d, Amy Berrington de Gonzalez, DPhil ^c, Kimberly A Bertrand, ScD ^e, William J Blot, PhD ^f, Jessica Clague DeHart, PhD ^g, Fergus J Couch, PhD ^h, Montserrat Garcia-Closas, MD DrPH ^c, Graham G Giles, PhD ^i,^j,^k, Victoria A Kirsh, PhD ^l,^m, Cari M Kitahara, PhD ⁿ, Woon-Puay Koh, PhD ^o,^p, Hannah Lui Park, PhD ^q,^r, Roger L Milne, PhD ^i,^j,^k, Julie R Palmer, ScD ^e, Alpa V Patel, PhD ^s, Thomas E Rohan, MBBS DHSc ^t, Minouk J Schoemaker, PhD ^c,^u, Anthony J Swerdlow, PhD ^c,^v, Lauren R Teras, PhD ^s, Celine Vachon, PhD ^w, Kala Visvanathan, MD MHS ^x, Jian-Min Yuan, MD PhD ^y,^z, Wei Zheng, MD PhD ^f, Hazel B Nichols, PhD ^aa, Dale P Sandler, PhD ^a

^a Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

^b Westat, Durham, NC, USA

^c Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK

^d Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

^e Slone Epidemiology Center, Boston University, Boston, MA, USA

^f Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

^g School of Community and Global Health, Claremont Graduate University, Claremont, CA, USA

^h Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

ⁱ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia

^j Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Australia

^k Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia

^l Ontario Institute for Cancer Research, Toronto, ON, Canada

^m Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

ⁿ Radiation Epidemiology Branch, National Cancer Institute, Rockville, MD, USA

^o Yong Loo Lin School of Medicine, National University of Singapore, Singapore

^p Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore

^q Department of Pathology and Laboratory Medicine, UC Irvine School of Medicine, Irvine, CA, USA

^r Department of Epidemiology, UC Irvine School of Medicine, Irvine, CA, USA

^s Department of Population Science, American Cancer Society, Atlanta, GA, USA

^t Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA

^u Real World Solutions, IQVIA, Amsterdam, Netherlands

^v Division of Breast Cancer Research, Institute of Cancer Research, London, UK

^w Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA

^x Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

^y University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA

^z Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

^aa Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

^* Correspondence to: Dr Katie M O’Brien, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Epidemiology Branch National Institute of Environmental Health Sciences Research Triangle Park NC 27709 USA

Summary

Background

Oestrogen plus progestin hormone therapy is an established risk factor for breast cancer in postmenopausal women. We examined the less well-studied association between exogenous hormones and breast cancer in young women, who might use hormone therapy after gynaecological surgery or to relieve perimenopausal symptoms.

Methods

In this pooled cohort analysis, we investigated the relationship between exogenous hormones and breast cancer in young women using data from 10–13 prospective cohorts from North America, Europe, Asia, and Australia. The participating cohorts followed up women for incident breast cancer until age 55 years. We used cohort-stratified, multivariable-adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CI for associations of hormone therapy with incident young-onset breast cancer. We also estimated risk differences based on cumulative risk until age 55 years.

Findings

We included 459 476 women aged 16–54 years (mean 42·0 years [IQR 35·5–49·2]), of whom 8455 (2%) developed young-onset breast cancer (diagnosed before age 55 years; median follow-up 7·8 years [5·2–11·2]). Overall, 15% of participants reported using hormone therapy, with oestrogen plus progestin hormone therapy (6%) and unopposed oestrogen (5%) being the most common types. Cumulative risk of young-onset breast cancer was 4·1% in non-users. Hormone therapy of any type was not associated with incident young-onset breast cancer (HR 0·96 [95% CI 0·88 to 1·04]), but ever oestrogen hormone therapy use was inversely associated (0·86 [0·75 to 0·98]; risk difference –0·5% [–1·0 to –0·0]). The HR for ever oestrogen plus progestin hormone therapy and young-onset breast cancer was 1·10 (0·98 to 1·24), with positive associations observed for long-term use (1·18 [1·01 to 1·38] for >2 years) and use among women without hysterectomy or bilateral oophorectomy (1·15 [1·02 to 1·31]). Oestrogen hormone therapy and young-onset breast cancer association was similar for all breast cancer subtypes, but oestrogen plus progestin hormone therapy was more strongly associated with oestrogen receptor negative (1·44 [1·11 to 1·88]) and triple-negative disease (1·50 [1·02 to 2·20]) than with other subtypes.

Interpretation

Oestrogen hormone therapy use was inversely associated with young-onset breast cancer, and oestrogen plus progestin hormone therapy was associated with higher young-onset breast cancer incidence among women with intact uterus and ovaries. These findings largely parallel results from studies of hormone use and later-onset breast cancer and provide novel evidence for establishing clinical recommendations among younger women.

Funding

NIH Intramural Research Program.

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Vol 26 - N° 7

P. 911-923 - juillet 2025 Retour au numéro

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Hormone therapy use and young-onset breast cancer: a pooled analysis of prospective cohorts included in the Premenopausal Breast Cancer Collaborative Group - 01/07/25

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