Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway

Nathalie C Støer; Siri Vangen; Deependra Singh; Renée T Fortner; Solveig Hofvind; Giske Ursin; Edoardo Botteri

doi:10.1038/s41416-024-02590-1

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway

Br J Cancer. 2024 May 13. doi: 10.1038/s41416-024-02590-1. Online ahead of print.

Authors

Nathalie C Støer^{1

2}, Siri Vangen^{3

4}, Deependra Singh^{3

5}, Renée T Fortner^{6

7}, Solveig Hofvind^{8

9}, Giske Ursin^{10

11

12}, Edoardo Botteri^{6

13}

Affiliations

¹ Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway. nacst@kreftregisteret.no.
² Norwegian Research Centre for Women's Health, Division of Obstetrics and Gynecology, Oslo University Hospital, Oslo, Norway. nacst@kreftregisteret.no.
³ Norwegian Research Centre for Women's Health, Division of Obstetrics and Gynecology, Oslo University Hospital, Oslo, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Cancer Surveillance Branch, International Agency for Research on Cancer, WHO, Lyon, France.
⁶ Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.
⁷ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁸ Section for Breast Cancer Screening, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.
⁹ Department of Health and Care Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
¹⁰ Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.
¹¹ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
¹² Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
¹³ Section for Colorectal Cancer Screening, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.

PMID: 38740969
DOI: 10.1038/s41416-024-02590-1

Abstract

Background: It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs.

Methods: We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference.

Results: We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31-2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35-1.96) to Kliogest®: 2.67 (2.37-3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86-2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83-2.30) than screen-detected (HR 1.33, 95% CI 1.26-1.41) BC in women 50-71 years. HRs for HT use decreased with increasing BMI.

Conclusions: The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.