Recreational Physical Activity and Outcomes After Breast Cancer in Women at High Familial Risk

Author:

Kehm Rebecca D1ORCID,MacInnis Robert J23ORCID,John Esther M4ORCID,Liao Yuyan1,Kurian Allison W5ORCID,Genkinger Jeanine M16ORCID,Knight Julia A78,Colonna Sarah V9ORCID,Chung Wendy K610ORCID,Milne Roger2311ORCID,Zeinomar Nur12ORCID,Dite Gillian S2ORCID,Southey Melissa C31113ORCID,Giles Graham G2311ORCID,McLachlan Sue-Anne1415ORCID,Whitaker Kristen D16ORCID,Friedlander Michael L1718ORCID,Weideman Prue C2,Glendon Gord7ORCID,Nesci Stephanie19,Phillips Kelly-Anne21920ORCID,Andrulis Irene L721ORCID,Buys Saundra S22ORCID,Daly Mary B16,Hopper John L2ORCID,Terry Mary Beth16ORCID,

Affiliation:

1. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA

2. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia

3. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia

4. Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA

5. Division of Medical Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

6. Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA

7. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada

8. Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

9. Division of Medical Oncology, Huntsman Cancer Institute, Salt Lake City, UT, USA

10. Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA

11. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia

12. Cancer Epidemiology and Health Outcomes, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA

13. Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia

14. Department of Medicine, St Vincent’s Hospital, The University of Melbourne, Melbourne, Victoria, Australia

15. Department of Medical Oncology, St Vincent’s Hospital, Fitzroy, Melbourne, Victoria, Australia

16. Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA

17. Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia

18. Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales, Australia

19. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

20. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia

21. Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

22. Department of Medicine and Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT, USA

Abstract

Abstract Background Recreational physical activity (RPA) is associated with improved survival after breast cancer (BC) in average-risk women, but evidence is limited for women who are at increased familial risk because of a BC family history or BRCA1 and BRCA2 pathogenic variants (BRCA1/2 PVs). Methods We estimated associations of RPA (self-reported average hours per week within 3 years of BC diagnosis) with all-cause mortality and second BC events (recurrence or new primary) after first invasive BC in women in the Prospective Family Study Cohort (n = 4610, diagnosed 1993-2011, aged 22-79 years at diagnosis). We fitted Cox proportional hazards regression models adjusted for age at diagnosis, demographics, and lifestyle factors. We tested for multiplicative interactions (Wald test statistic for cross-product terms) and additive interactions (relative excess risk due to interaction) by age at diagnosis, body mass index, estrogen receptor status, stage at diagnosis, BRCA1/2 PVs, and familial risk score estimated from multigenerational pedigree data. Statistical tests were 2-sided. Results We observed 1212 deaths and 473 second BC events over a median follow-up from study enrollment of 11.0 and 10.5 years, respectively. After adjusting for covariates, RPA (any vs none) was associated with lower all-cause mortality of 16.1% (95% confidence interval [CI] = 2.4% to 27.9%) overall, 11.8% (95% CI = -3.6% to 24.9%) in women without BRCA1/2 PVs, and 47.5% (95% CI = 17.4% to 66.6%) in women with BRCA1/2 PVs (RPA*BRCA1/2 multiplicative interaction P = .005; relative excess risk due to interaction = 0.87, 95% CI = 0.01 to 1.74). RPA was not associated with risk of second BC events. Conclusion Findings support that RPA is associated with lower all-cause mortality in women with BC, particularly in women with BRCA1/2 PVs.

Funder

USA National Cancer Institute

kConFab and the kConFab Follow-Up Study from Cancer Australia

Australian National Breast Cancer Foundation

National Health and Medical Research Council

National Institute of Health USA

Queensland Cancer Fund

Cancer Councils of New South Wales, Victoria, Tasmania and South Australia

Cancer Foundation of Western Australia

KAP is a National Health and Medical Research Council Leadership Fellow

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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