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Menstrual and reproductive history, postmenopausal hormone use, and risk of benign proliferative epithelial disorders of the breast: a cohort study

  • Epidemiology
  • Published:
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Abstract

Menstrual and reproductive history and postmenopausal hormone use are well-established risk factors for breast cancer. However, previous studies that have assessed these factors in association with risk of benign proliferative epithelial disorders (BPED) of the breast, putative precursors of breast cancer, have yielded inconsistent findings. To investigate these associations, we conducted a cohort study among 68,132 postmenopausal women enrolled in the Women’s Health Initiative randomized clinical trials. Women were prospectively followed and those reporting an open surgical biopsy or a core needle biopsy had histological sections obtained for centralized pathology review. Over an average of 7.8 years of follow-up, we identified 1,792 women with BPED of the breast. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence limits (CLs) for the associations of interest. Menstrual and reproductive histories were not associated with risk of BPED of the breast, overall or by histological subtype. Women who had used postmenopausal hormones for 15 years or more had a two-fold increase in risk of BPED of the breast compared to women who had never used postmenopausal hormones (HR = 2.03 95% CL = 1.73, 2.38) and the increase in risk was observed for both BPED of the breast without atypia and for atypical hyperplasia. Furthermore, the risk of BPED of the breast decreased with time since cessation of use so that there was essentially no increase in risk 5 or more years after ending use (HR for stopping ≥5 years earlier = 0.96, 95%CL = 0.79, 1.16; HR for stopping <5 years earlier = 1.32, 95% CL = 1.08,1.61).

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Acknowledgments

The study is supported by NIH grant RO1-CA77290.We are indebted to the participants and investigators in the Women’s Health Initiative Clinical Trial. We also thank Mindy Ginsberg and Mary Pettinger for managing the datasets.

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Authors and Affiliations

  1. Office of Health Assessment and Epidemiology, Los Angeles County Department of Public Health, 313 N. Figueroa Street, Suite 127, Los Angeles, CA, 90012, USA

    Yan Cui

  2. Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    David L. Page

  3. Department of Preventive Medicine, Stony Brook University School of Medicine, Stony Brook, NY, 11794, USA

    Dorothy S. Lane

  4. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Thomas E. Rohan

Authors
  1. Yan Cui
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  2. David L. Page
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  3. Dorothy S. Lane
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  4. Thomas E. Rohan
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Corresponding author

Correspondence to Yan Cui.

Appendix

Appendix

List of participating WHI investigators: Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Barbara Alving, Jacques Rossouw, Shari Ludlam, Linda Pottern, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L. Kooperberg, Ruth E. Patterson, Anne McTiernan; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker; (Medical Research Labs, Highland Heights, KY) Evan Stein; (University of California at San Francisco, San Francisco, CA) Steven Cummings. Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX) Jennifer Hays; (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn Manson; (Brown University, Providence, RI) Annlouise R. Assaf; (Emory University, Atlanta, GA) Lawrence Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Judith Hsia; (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Evelyn Whitlock; (Kaiser Permanente Division of Research, Oakland, CA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Northwestern University, Chicago/Evanston, IL) Linda Van Horn; (Rush Medical Center, Chicago, IL) Henry Black; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (State University of New York at Stony Brook, Stony Brook, NY) Dorothy Lane; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL) Cora E. Lewis; (University of Arizona, Tucson/Phoenix, AZ) Tamsen Bassford; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA) John Robbins; (University of California at Irvine, CA) F. Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA) Howard Judd; (University of California at San Diego, LaJolla/Chula Vista, CA) Robert D. Langer; (University of Cincinnati, Cincinnati, OH) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Hawaii, Honolulu, HI) David Curb; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ) Norman Lasser; (University of Miami, Miami, FL) Mary Jo O’Sullivan; (University of Minnesota, Minneapolis, MN) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (University of Tennessee, Memphis, TN) Karen C. Johnson; (University of Texas Health Science Center, San Antonio, TX) Robert Brzyski; (University of Wisconsin, Madison, WI) Gloria E. Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC) Denise Bonds; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Susan Hendrix.

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Cui, Y., Page, D.L., Lane, D.S. et al. Menstrual and reproductive history, postmenopausal hormone use, and risk of benign proliferative epithelial disorders of the breast: a cohort study. Breast Cancer Res Treat 114, 113–120 (2009). https://doi.org/10.1007/s10549-008-9973-9

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