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Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women’s Health Initiative

  • Epidemiology
  • Published:
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Abstract

Background

Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women’s Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years).

Methods

Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates.

Results

After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32–8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80–1.16, P = 0.68) with similar findings by age.

Conclusions

In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.

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Data availability

The following data will be made available beginning 1 July 2025: the identified participant data and data dictionary (information about data sharing for the Women’s Health Initiative can be found at: www.WHI.orgy/researchers/data/Documents/WHI%20 Data%20 Sharing%20 Statement.pdf. For these analyses, data will be publicly available two years after publication of this article. The following supporting documents are available: statistical/analytical and informed consent form (www.whi.org/researchers/studydoc/SitePages/Protocol%20 and% 20Consents.aspx).

Prior Presentation: Some of the findings were presented on March 18, 2021, at the Virtual St Gallen Breast Cancer Meeting.

Additional contributions: We thank the WHI investigators, staff, and the trial participants for their outstanding dedication and commitment. Program Office: Jacques Roscoe, Shari Ludlum, Dale Burden, Joan McGowan, Leslie Ford, and Nancy Geller (National Heart, Lung, and Blood Institute, Bethesda, MD) Clinical Coordinating Center: Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kopperberg (Fred Hutchinson Cancer Research Center, Seattle, WA) Investigators and Academic Centers: JoAnn E. Manson (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA); Barbara V. Howard (MedStar Health Research Institute/Howard University, Washington, DC); Marcia L. Stefanick (Stanford Prevention Research Center, Stanford, CA); Rebecca Jackson (The Ohio State University, Columbus, OH); Cynthia A. Thompson (University of Arizona, Tucson/Phoenix, AZ); Jean Wactawski-Wende (University at Buffalo, Buffalo, NY); Marian Limacher (University of Florida, Gainesville/Jacksonville, FL); Robert Wallace (University of Iowa, Iowa City/Davenport, IA); Lewis Kuller (University of Pittsburgh, Pittsburgh, PA); Rowan T. Chlebowski (The Lundquist Institute, Torrance, CA), and Sally Shumaker (Wake Forest University School of Medicine, Winston-Salem, NC).

A full list of all the investigators who have contributed to WHI science can be retrieved: https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator %20Long%20List.pdf.

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Funding

The WHI program is supported by the National Heart, Lung and Blood Institute, National Institutes of Health, 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. HHSN268201600003C, HHSN268201600004C and R25CA203650 also partially supported the development of this paper.

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Authors and Affiliations

  1. The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA

    Kathy Pan, Rebecca A. Nelson, Rowan T. Chlebowski, Rita Piela, Maeve Mullooly, Michael S. Simon, Thomas E. Rohan, Jean Wactawski-Wende, JoAnn E. Manson, Joanne E. Mortimer, Dorothy Lane & Laura Kruper

Authors
  1. Kathy Pan
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Contributions

KP wrote the analysis proposal and initial draft of the report. KP, RC, and RAN had full access to study data and take full responsibility for the integrity of the data and the accuracy of the analysis. RAN undertook the statistical analysis. All authors including KP, RTC, RN, LK, JEMo, MSS, TER, RP, JEMa, DL, MM, and JWW provided critical review of the manuscript for important intellectual content. RTC, MSS, JW, JEMa, TER, and DL collected the data and obtained study funding.

Corresponding author

Correspondence to Rowan T. Chlebowski.

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Conflict of interest

Dr Chlebowski is a consultant for Novartis, AstraZeneca, Pfizer and UpToDate. No other author reported conflicts.

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Pan, K., Nelson, R.A., Chlebowski, R.T. et al. Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women’s Health Initiative. Breast Cancer Res Treat (2024). https://doi.org/10.1007/s10549-024-07327-5

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