Menopausal hormone therapy: assessing associations with breast and colorectal cancers by familial risk

Robert J Macinnis; Mark A Jenkins; Roger L Milne; Esther M John; Mary B Daly; Irene L Andrulis; Sarah V Colonna; Kelly A Phillips; Kconfab Investigators; Loic Le Marchand; Polly A Newcomb; Amanda Phipps; Stephanie Schmit; Finlay Macrae; Daniel Buchanan; Steven Gallinger; Rish K Pai; Niloy J Samadder; Graham G Giles; Melissa C Southey; John L Hopper; Mary Beth Terry

doi:10.1093/jncics/pkae121

Menopausal hormone therapy: assessing associations with breast and colorectal cancers by familial risk

JNCI Cancer Spectr. 2024 Dec 3:pkae121. doi: 10.1093/jncics/pkae121. Online ahead of print.

Authors

Robert J Macinnis^{1

2}, Mark A Jenkins^{2

3}, Roger L Milne^{1

2

4}, Esther M John^{5

6

7}, Mary B Daly⁸, Irene L Andrulis⁹, Sarah V Colonna¹⁰, Kelly A Phillips^{11

12}; Kconfab Investigators; Loic Le Marchand, Polly A Newcomb^{13

14}, Amanda Phipps^{13

14}, Stephanie Schmit^{15

16}, Finlay Macrae¹⁷, Daniel Buchanan^{3

18

19}, Steven Gallinger^{9

20

21}, Rish K Pai²², Niloy J Samadder²³, Graham G Giles^{1

2

24}, Melissa C Southey^{1

4

25}, John L Hopper², Mary Beth Terry^{26

27}

Affiliations

¹ Cancer Epidemiology Division, Cancer Council Victoria, East Melbourne, Victoria, Australia.
² Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia.
³ Cancer Research Centre, University of Melbourne, Parkville, Victoria, Australia.
⁴ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
⁵ Department of Epidemiology & Population Health, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA, USA.
⁷ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁹ Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
¹¹ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹² Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia.
¹³ Epidemiology Department, University of Washington, Seattle, WA, USA.
¹⁴ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁵ Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
¹⁶ Case Comprehensive Cancer Center, Cleveland, OH, USA.
¹⁷ Department of Colorectal Medicine and Genetics, Royal Melbourne Hospital, Victoria, Australia.
¹⁸ Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
¹⁹ Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
²⁰ Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
²¹ Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada.
²² Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
²³ Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA.
²⁴ Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
²⁵ Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
²⁶ Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
²⁷ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

PMID: 39673461
DOI: 10.1093/jncics/pkae121

Abstract

Menopausal hormone therapy (MHT) users are at increased breast cancer (BC) risk and decreased colorectal cancer (CRC) risk compared with never users, but these opposing associations might differ by familial risk of BC and CRC. We harmonized data from three cohorts and generated separate BC and CRC familial risk scores (FRS) based on cancer family history. We defined moderate/strong family history as FRS ≥ 0.4, where 0.4 was equivalent to a 50-year-old woman with one parent diagnosed with either cancer at age 55 years. Of 24,486 women, 1,243 and 405 were diagnosed with incident BC and CRC, respectively. For BC, MHT hazard ratios (HRs) were 1.27 (95%CI = 1.11-1.45) for FRSBC<0.4, 1.01 (95%CI = 0.82-1.25) for FRSBC≥0.4 (P-difference = 0.08). For CRC, MHT HRs were 0.63 (95%CI = 0.50-0.78) for FRSCRC<0.4, 1.21 (95%CI = 0.73-2.00) for FRSCRC≥0.4 (P-difference = 0.03). Associations with MHT that apply to the general population might not hold for women at moderate/strong familial risk of these cancers.