• Anne S Reiner, Julia Sisti, Esther M John, Charles F Lynch, Jennifer D Brooks, Lene Mellemkjær, John D Boice, Julia A Knight, Patrick Concannon, Marinela Capanu, Marc Tischkowitz, Mark Robson, Xiaolin Liang, Meghan Woods, David V Conti, David Duggan, Roy Shore, Daniel O Stram, Duncan C Thomas, Kathleen E Malone, Leslie Bernstein, WECARE Study Collaborative Group, and Jonine L Bernstein.
• Anne S. Reiner, Julia Sisti, Marinela Capanu, Mark Robson, Xiaolin Liang, Meghan Woods, and Jonine L. Bernstein, Memorial Sloan Kettering Cancer Center; Mark Robson, Cornell University; Roy Shore, New York University School of Medicine, New York, NY; Esther M. John, Cancer Prevention Institute of California, Fremont, and Stanford School of Medicine, Stanford; David V. Conti, Daniel O. Stram, and Duncan C. Thomas, University of Southern California, Los Angeles; Leslie Bernstein, City of Hope National Medical Center, Duarte, CA; Charles F. Lynch, University of Iowa, Iowa City, IA; Jennifer D. Brooks and Julia A. Knight, University of Toronto; Julia A. Knight, Sinai Health System, Toronto, Ontario, Canada; Lene Mellemkjær, Danish Cancer Society Research Center, Copenhagen, Denmark; John D. Boice, Vanderbilt University Medical Center and the Vanderbilt-Ingram Cancer Center, Nashville, TN; Patrick Concannon, University of Florida, Gainesville, FL; Marc Tischkowitz, University of Cambridge, Cambridge, United Kingdom; David Duggan, Translational Genomics Research Institute, Phoenix, AZ; and Kathleen E. Malone, Fred Hutchinson Cancer Research Center, Seattle, WA.
• J. Clin. Oncol. 2018 May 20; 36 (15): 1513-1520.

AbstractPurpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer.

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