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Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 mutation

  • Joanne Kotsopoulos
    Affiliations
    Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada

    Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
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  • Jacek Gronwald
    Affiliations
    Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
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  • Jeanna M. McCuaig
    Affiliations
    Division of Gynecologic Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada
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  • Beth Y. Karlan
    Affiliations
    Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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  • Andrea Eisen
    Affiliations
    Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada
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  • Nadine Tung
    Affiliations
    Beth Israel Deaconess Medical Center, Boston, MA, USA
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  • Louise Bordeleau
    Affiliations
    Department of Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, ON, Canada
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  • Leigha Senter
    Affiliations
    Division of Human Genetics, the Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA
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  • Charis Eng
    Affiliations
    Genomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Center for Personalised Genetic Healthcare, Cleveland Clinic Community Care and Population Health, Cleveland, OH, USA
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  • Fergus Couch
    Affiliations
    Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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  • Robert Fruscio
    Affiliations
    Department of Medicine and Surgery, University of Milan Bicocca, Monza, Italy
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  • Jeffrey N. Weitzel
    Affiliations
    Division of Clinical Cancer Genomics, Department of Population Sciences, City of Hope, Duarte, CA, USA
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  • Olufunmilayo Olopade
    Affiliations
    Department of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA
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  • Christian F. Singer
    Affiliations
    Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
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  • Tuya Pal
    Affiliations
    Department of Medicine, Vanderbilt University, Nashville, TN, USA
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  • William D. Foulkes
    Affiliations
    Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, QC, Canada
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  • Susan L. Neuhausen
    Affiliations
    Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, City of Hope, Duarte, CA, USA
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  • Ping Sun
    Affiliations
    Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada
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  • Jan Lubinski
    Affiliations
    Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
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  • Steven A. Narod
    Correspondence
    Corresponding author at: Women's College Research Institute, Women's College Hospital, 76 Grenville St., 6th Floor, Toronto, ON M5S 1B2, Canada.
    Affiliations
    Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada

    Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
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  • the Hereditary Ovarian Cancer Clinical Study Group
    Author Footnotes
    1 Other members of the Hereditary Ovarian Cancer Clinical Study Group: Tomasz Huzarski, Cezary Cybulski, Barry Rosen, Kevin Sweet, Dana Zakalik, Marie Wood, Wendy McKinnon, Christine Elser, Georgia Wiesner, Eitan Friedman, Wendy Meschino, Carrie Snyder, Kelly Metcalfe, Aletta Poll, Ellen Warner, Raymond Kim, Susan Armel, Rochelle Demsky, Peter Ainsworth, Linda Steele, Howard Saal, Kim Serfas, Seema Panchal, Carey A. Cullinane, Robert E. Reilly, Joanne L. Blum, Ava Kwong, Daniel Rayson, Teresa Ramón y Cajal, Jeffrey Dungan, Pal Moller, Rinat Yerushalmi, Ophira Ginsburg, Sophie Sun, Intan Schraeder, Stephanie Cohen, Edmond Lemire, Stefania Zovato and Antonella Rastelli
  • Author Footnotes
    1 Other members of the Hereditary Ovarian Cancer Clinical Study Group: Tomasz Huzarski, Cezary Cybulski, Barry Rosen, Kevin Sweet, Dana Zakalik, Marie Wood, Wendy McKinnon, Christine Elser, Georgia Wiesner, Eitan Friedman, Wendy Meschino, Carrie Snyder, Kelly Metcalfe, Aletta Poll, Ellen Warner, Raymond Kim, Susan Armel, Rochelle Demsky, Peter Ainsworth, Linda Steele, Howard Saal, Kim Serfas, Seema Panchal, Carey A. Cullinane, Robert E. Reilly, Joanne L. Blum, Ava Kwong, Daniel Rayson, Teresa Ramón y Cajal, Jeffrey Dungan, Pal Moller, Rinat Yerushalmi, Ophira Ginsburg, Sophie Sun, Intan Schraeder, Stephanie Cohen, Edmond Lemire, Stefania Zovato and Antonella Rastelli
Published:September 30, 2020DOI:https://doi.org/10.1016/j.ygyno.2020.09.037

      Highlights

      • Whether a history of breastfeeding is associated with the risk of ovarian cancer among BRCA mutation carriers is not known.
      • In this matched analysis, ever-breastfeeding was associated with a significant 23% reduction in risk of ovarian cancer.
      • We observed an additive effect of both oral contraceptive use and breastfeeding which was strongly protective.
      • Delineating the underlying mechanism(s) conferring the protective effect of breastfeeding is necessary.

      Abstract

      Objective

      BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation.

      Method

      Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures.

      Results

      A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66–0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57–0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37–0.58; P < 0.0001).

      Conclusions

      These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.

      Keywords

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