Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in <i>BRCA1</i> and <i>BRCA2</i>
Abstract
PURPOSE It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline BRCA1 or BRCA2 mutation carriers. METHODS Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers were assessed using Cox regression. RESULTS Of 3,882 BRCA1 and 1,509 BRCA2 mutation carriers, 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 BRCA1 and 191 BRCA2 mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for BRCA1 mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], P = .10 for current use; 1.16 [0.80 to 1.69], P = .4, 1.40 [0.99 to 1.97], P = .05, and 1.27 [0.98 to 1.63], P = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], P = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, P = .002) for each additional year of use. For BRCA2 mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively). CONCLUSION Hormonal contraceptives were associated with increased BC risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (145)
Kelly-Anne Phillips
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Joanne Kotsopoulos
Women's College Research Institute, University of Toronto, Toronto, ON, Canada
Susan M. Domchek
Mary Beth Terry
James A. Chamberlain
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
Julie K. Bassett
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
Amber M. Aeilts
Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio
Irene L. Andrulis
Saundra S. Buys
Wanda Cui
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Mary B. Daly
Andrea F. Eisen
Odette Cancer Centre, Sunnybrook Health Sciences, Toronto, ON, Canada
William D. Foulkes
Michael L. Friedlander
Jacek Gronwald
John L. Hopper
Esther M. John
Beth Y. Karlan
Raymond H. Kim
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Allison W. Kurian
Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA
Jan Lubiński
Kelly Metcalfe
Women's College Research Institute, University of Toronto, Toronto, ON, Canada
Katherine L. Nathanson
Christian F. Singer
Melissa C. Southey
Heather Symecko
Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA
Nadine Tung
Steven A. Narod
Women's College Hospital, Toronto, ON, Canada
Roger L. Milne
David Amor
Lesley Andrews
Yoland Antill
Rosemary Balleine
Jonathan Beesley
Ian Bennett
Michael Bogwitz
Simon Bodek
Leon Botes
Meagan Brennan
Melissa Brown
Michael Buckley
Jo Burke
Phyllis Butow
Liz Caldon
Ian Campbell
Michelle Cao
Anannya Chakrabarti
Deepa Chauhan
Manisha Chauhan
Georgia Chenevix-Trench
Alice Christian
Paul Cohen
Alison Colley
Ashley Crook
James Cui
Eliza Courtney
Margaret Cummings
Sarah-Jane Dawson
Anna deFazio
Martin Delatycki
Rebecca Dickson
Joanne Dixon
Stacey Edwards
Gelareh Farshid
Andrew Fellows
Georgina Fenton
Michael Field
James Flanagan
Peter Fong
Laura Forrest
Stephen Fox
Juliet French
Michael Friedlander
Clara Gaff
Mike Gattas
Peter George
Sian Greening
Marion Harris
Stewart Hart
Philip Harraka
Nick Hayward
John Hopper
Cass Hoskins
Clare Hunt
Paul James
Mark Jenkins
Alexa Kidd
Judy Kirk
Jessica Koehler
James Kollias
Sunil Lakhani
Mitchell Lawrence
Jason Lee
Shuai Li
Geoff Lindeman
Jocelyn Lippey
Lara Lipton
Liz Lobb
Sherene Loi
Graham Mann
Deborah Marsh
Sue Anne McLachlan
Bettina Meiser
Roger Milne
Sophie Nightingale
Shona O'Connell
Sarah O'Sullivan
David Gallego Ortega
Nick Pachter
Jia-Min Pang
Gargi Pathak
Briony Patterson
Amy Pearn
Kelly Phillips
Ellen Pieper
Susan Ramus
Edwina Rickard
Abi Ragunathan
Bridget Robinson
Mona Saleh
Anita Skandarajah
Elizabeth Salisbury
Christobel Saunders
Jodi Saunus
Peter Savas
Rodney Scott
Clare Scott
Adrienne Sexton
Joanne Shaw
Andrew Shelling
Shweta Srinivasa
Peter Simpson
Melissa Southey
Amanda Spurdle
Jessica Taylor
Renea Taylor
Heather Thorne
Alison Trainer
Kathy Tucker
Jane Visvader
Logan Walker
Rachael Williams
Ingrid Winship
Mary Ann Young
Milita Zaheed