Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in
BRCA1
and
BRCA2
Authors: Phillips Kelly-Anne , Kotsopoulos Joanne , Domchek Susan M. , Terry Mary Beth , Chamberlain James A. , Bassett Julie K. , Aeilts Amber M. , Andrulis Irene L. , Buys Saundra S. , Cui Wanda , Daly Mary B. , Eisen Andrea F. , Foulkes William D. , Friedlander Michael L. , Gronwald Jacek , Hopper John L. , John Esther M. , Karlan Beth Y. , Kim Raymond H. , Kurian Allison W. , Lubinski Jan , Metcalfe Kelly , Nathanson Katherine L. , Singer Christian F. , Southey Melissa C. , Symecko Heather , Tung Nadine , Narod Steven A. , Milne Roger L. ,   for the Kathleen Cuningham Foundation Consortium for Research Into Familial Breast Cancer, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study, the Basser Center University of Pennsylvania Registry, and the Breast Cancer Family Registry, Amor David , Andrews Lesley , Antill Yoland , Balleine Rosemary , Beesley Jonathan , Bennett Ian , Bogwitz Michael , Bodek Simon , Botes Leon , Brennan Meagan , Brown Melissa , Buckley Michael , Burke Jo , Butow Phyllis , Caldon Liz , Campbell Ian , Cao Michelle , Chakrabarti Anannya , Chauhan Deepa , Chauhan Manisha , Chenevix-Trench Georgia , Christian Alice , Cohen Paul , Colley Alison , Crook Ashley , Cui James , Courtney Eliza , Cummings Margaret , Dawson Sarah-Jane , DeFazio Anna , Delatycki Martin , Dickson Rebecca , Dixon Joanne , Edwards Stacey , Farshid Gelareh , Fellows Andrew , Fenton Georgina , Field Michael , Flanagan James , Fong Peter , Forrest Laura , Fox Stephen , French Juliet , Friedlander Michael , Gaff Clara , Gattas Mike , George Peter , Greening Sian , Harris Marion , Hart Stewart , Harraka Philip , Hayward Nick , Hopper John , Hoskins Cass , Hunt Clare , James Paul , Jenkins Mark , Kidd Alexa , Kirk Judy , Koehler Jessica , Kollias James , Lakhani Sunil , Lawrence Mitchell , Lee Jason , Li Shuai , Lindeman Geoff , Lippey Jocelyn , Lipton Lara , Lobb Liz , Loi Sherene , Mann Graham , Marsh Deborah , McLachlan Sue Anne , Meiser Bettina , Milne Roger , Nightingale Sophie , O'Connell Shona , O'Sullivan Sarah , Ortega David Gallego , Pachter Nick , Pang Jia-Min , Pathak Gargi , Patterson Briony , Pearn Amy , Phillips Kelly , Pieper Ellen , Ramus Susan , Rickard Edwina , Ragunathan Abi , Robinson Bridget , Saleh Mona , Skandarajah Anita , Salisbury Elizabeth , Saunders Christobel , Saunus Jodi , Savas Peter , Scott Rodney , Scott Clare , Sexton Adrienne , Shaw Joanne , Shelling Andrew , Srinivasa Shweta , Simpson Peter , Southey Melissa , Spurdle Amanda , Taylor Jessica , Taylor Renea , Thorne Heather , Trainer Alison , Tucker Kathy , Visvader Jane , Walker Logan , Williams Rachael , Winship Ingrid , Young Mary Ann , Zaheed Milita 
Published: October 2024

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.