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Effects of menopausal hormone therapy on ductal carcinoma in situ of the breast

  • Epidemiology
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Abstract

Post-menopausal hormone therapy with estrogen plus progestin is consistently reported to be associated with an increased risk of invasive breast cancer. However, findings on an association between hormone use and ductal carcinoma in situ of the breast (DCIS), a possible precursor lesion of invasive breast cancer, are sparse and inconsistent. Women’s Health Initiative data were used to assess the effects of hormone therapy on the risk of DCIS in two clinical trials of hormone therapy (16,276 women enrolled in the trial of daily conjugated equine estrogens plus medroxyprogesterone acetate (CEE + MPA) vs placebo; 10,187 women enrolled in the trial of CEE-alone vs placebo). The effects of hormone therapy on DCIS in clinical trial participants were assessed during the intervention, post-intervention, and entire followup periods, and in the observational study (OS; 30,421 CEE + MPA users and non-users and 18,657 CEE-alone users and non-users who met eligibility criteria similar to the clinical trial). Compared to placebo, CEE + MPA was non-significantly associated with higher risk of DCIS over approximate average of 11 years of follow-up (HR = 1.23; 95 % CI: 0.91–1.64). No statistical difference was detected between intervention and post-intervention phases (p = 0.32). Corresponding OS results supported an increased risk for DCIS in CEE + MPA users compared to women who were non-users (HR = 1.65; 95 % CI: 1.25–2.19) after adjusting for potential confounders. There was no clear association between CEE-alone use and risk of DCIS. CEE-alone trial data showed that the risk of DCIS was non-significantly lower in the treatment than in the placebo group, while analysis of the corresponding OS showed a non-significantly higher risk of DCIS in the CEE-alone users than non-users. Our analysis suggests that combined estrogen plus progestin use in post-menopausal women may increase risk of DCIS. Whether estrogen-alone use is associated with DCIS requires further investigation.

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Acknowledgments

The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.

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Correspondence to Juhua Luo.

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A short list of WHI investigators is given in an Appendix.

Appendix: Short list of WHI investigators

Appendix: Short list of WHI investigators

Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller.

Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA).

Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles Kooperberg; (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) Haleh Sangi-Haghpeykar; (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (Brown University, Providence, RI) Charles B. Eaton; (Emory University, Atlanta, GA) Lawrence S. Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Lisa Martin; (Los Angeles Biomedical Research Institute at Harbor—UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Erin LeBlanc; (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) Cynthia A. Thomson; (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) Lauren Nathan; (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) J. 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 Health Science Center, 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) Mara Vitolins; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Michael S. Simon.

Womens Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker.

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Luo, J., Cochrane, B.B., Wactawski-Wende, J. et al. Effects of menopausal hormone therapy on ductal carcinoma in situ of the breast. Breast Cancer Res Treat 137, 915–925 (2013). https://doi.org/10.1007/s10549-012-2402-0

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