A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study
Jennifer D. Brooks,
John D. Boice, Jr.,
Roy E. Shore,
Anne S. Reiner,
Susan A. Smith,
Leslie Bernstein,
Julia A. Knight,
Charles F. Lynch,
Esther M. John,
Kathleen E. Malone,
Lene Mellemkjaer,
Rikke Langballe,
Xiaolin Liang,
Meghan Woods,
Marc Tischkowitz,
Patrick Concannon,
Daniel O. Stram,
Jonine L. Bernstein
Affiliations
Jennifer D. Brooks
University of Toronto, Dalla Lana School of Public Health Sciences, Toronto, Canada; Corresponding author. 155 College St. HSB 676, University of Toronto, Toronto, ON, M5T 3M7, Canada.
John D. Boice, Jr.
Vanderbilt University Medical Center and the Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
Roy E. Shore
New York University School of Medicine, New York, NY, USA
Anne S. Reiner
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Susan A. Smith
The University of Texas M.D. Anderson Cancer Centre, Houston, TX, USA
Leslie Bernstein
Beckman Research Institute, City of Hope National Medical Centre, Duarte, CA, USA
Julia A. Knight
University of Toronto, Dalla Lana School of Public Health Sciences, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
Charles F. Lynch
University of Iowa, Iowa City, IA, USA
Esther M. John
Department of Epidemiology & Population Health and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
Kathleen E. Malone
Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Lene Mellemkjaer
Danish Cancer Society Research Center, Copenhagen, Denmark
Rikke Langballe
Danish Cancer Society Research Center, Copenhagen, Denmark
Xiaolin Liang
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Meghan Woods
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Marc Tischkowitz
Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK
Patrick Concannon
Genetics Institute and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
Daniel O. Stram
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Jonine L. Bernstein
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Objective: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC). Methods: The Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity). Results: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast. Conclusion: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman’s risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.
