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Int J Cancer. 2019 Feb 6. doi: 10.1002/ijc.32112. [Epub ahead of print]

Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort.

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Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.
Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC, Australia.
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA.
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia.
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY.
Department of Pediatrics and Medicine, Columbia University, New York, NY.
Department of Medicine, St Vincent's Hospital, The University of Melbourne, Parkville, VIC, Australia.
Department of Medical Oncology, St Vincent's Hospital, Fitzroy, VIC, Australia.
Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
Department of Medical Oncology, Prince of Wales Hospital, Randwick, NSW, Australia.
The Research Department, The Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Department of Medicine and Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT.
Department of Medicine and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA.


Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of BBD with BC risk. We also examined whether the association with BBD differed by underlying familial risk profile (FRP), calculated using absolute risk estimates from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. During 176,756 person-years of follow-up (median: 10.9 years, maximum: 23.7) of 17,154 women unaffected with BC at baseline, we observed 968 incident cases of BC. A total of 4,704 (27%) women reported a history of BBD diagnosis at baseline. A history of BBD was associated with a greater risk of BC: HR = 1.31 (95% CI: 1.14-1.50), and did not differ by underlying FRP, with HRs of 1.35 (95% CI: 1.11-1.65), 1.26 (95% CI: 1.00-1.60), and 1.40 (95% CI: 1.01-1.93), for categories of full-lifetime BOADICEA score <20%, 20 to <35%, ≥35%, respectively. There was no difference in the association for women with BRCA1 mutations (HR: 1.64; 95% CI: 1.04-2.58), women with BRCA2 mutations (HR: 1.34; 95% CI: 0.78-2.3) or for women without a known BRCA1 or BRCA2 mutation (HR: 1.31; 95% CI: 1.13-1.53) (pinteraction  = 0.95). Women with a history of BBD have an increased risk of BC that is independent of, and multiplies, their underlying familial and genetic risk.


Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm; benign breast disease; breast cancer; familial risk


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