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Clinical Study

Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women’s Health Initiative (WHI) randomised trial

British Journal of Cancer volume 125, pages 372–379 (2021)Cite this article

Subjects

Abstract

Background

In the Women’s Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components.

Methods

In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score.

Results

HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63–1.87; with 1–2 MS components (n = 30,948), HR 0.80, 95% CI 0.62–1.02; with 3–4 MS components (n = 4,246), HR 0.31, 95% CI 0.14–0.69 (interaction P = 0.01).

Conclusions

While postmenopausal women with 3–4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk.

Registry

ClinicalTrials.gov (NCT00000611).

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Fig. 1: Subgroup analysis by a forest plot of hazard ratios (HRs), dietary intervention versus comparison, for death from breast cancer by select subgroups of participants throughout the cumulative follow-up period.
Fig. 2: Subgroup analysis by a forest plot of hazard ratios (HRs), dietary intervention versus comparison, for death after breast cancer by select subgroups of participants throughout the cumulative follow-up period.

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Acknowledgements

Prior presentation: Some of the findings were presented on June 1, 2019, at the American Society of Clinical Oncology Annual Meeting. The authors acknowledge the following investigators in the WHI Program: Program Office (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford and Nancy Geller. Clinical Coordinating Center: Fred Hutchinson Cancer Research Center, Seattle, WA, Garnet Anderson, Ross Prentice, Andrea LaCroix and Charles Kooperberg. Investigators and Academic Centers (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA), JoAnn E. Manson (MedStar Health Research Institute/Howard University, Washington, DC), Barbara V. Howard (Stanford Prevention Research Center, Stanford, CA), Marcia L. Stefanick (The Ohio State University, Columbus, OH), Rebecca Jackson (University of Arizona, Tucson/Phoenix, AZ), Cynthia A. Thomson (University at Buffalo, Buffalo, NY), Jean Wactawski-Wende (University of Florida, Gainesville/Jacksonville, FL), Marian Limacher (University of Iowa, Iowa City/Davenport, IA), Robert Wallace (University of Pittsburgh, Pittsburgh, PA), Lewis Kuller (Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA), Rowan T. Chlebowski (Wake Forest University School of Medicine, Winston-Salem, NC), Sally Shumaker Women’s Health Initiative Memory Study (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker. For a list of all the investigators who have contributed to WHI science, please visit http://www.whi.org/publications/WHI_investigators_longlist.pdf. Additional contributions: we thank the Women’s Health Initiative investigators, staff and the trial participants for their outstanding dedication and commitment.

Author information

Authors and Affiliations

  1. Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA

    Kathy Pan & Rowan T. Chlebowski

  2. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Aaron K. Aragaki & Marian L. Neuhouser

  3. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Michael S. Simon

  4. Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Michael S. Simon

  5. University of Indiana, Bloomington, IN, USA

    Juhua Luo

  6. Kaiser Permanente Northern California Division of Research, Oakland, CA, USA

    Bette Caan & Candyce Kroenke

  7. University of Iowa, Bloomington, IN, USA

    Linda Snetselaar

  8. City of Hope National Medical Center, Duarte, CA, USA

    Joanne E. Mortimer

  9. Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA

    JoAnn E. Manson

  10. State University of New York at Stony Brook, Stony Brook, NY, USA

    Dorothy Lane

  11. Fred Hutchinson Cancer Research Center & University of Washington, School of Nursing, Seattle, WA, USA

    Kerryn Reding

  12. Albert Einstein College of Medicine, Bronx, NY, USA

    Thomas E. Rohan

Authors
  1. Kathy Pan
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Contributions

Conceived the work that led to the submission: K.P., R.T.C. and J.E. Mortimer. Drafting of the paper: K.P. and R.T.C. Statistical analysis: A.K.A. Acquisition of data: A.K.A., M.L.N., M.S.S., B.C., L.S., J.E. Manson, D.L., T.E.R., K.R., C.K. and R.T.C. Played an important role in interpreting the results: K.P., A.K.A., R.T.C., J.L. and J.E. Manson. Critical revision of the paper for important intellectual content: all authors. Approved the final version: all authors. Agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors.

Corresponding author

Correspondence to Kathy Pan.

Ethics declarations

Ethics approval and consent to participate

The WHI project was reviewed and approved by the Fred Hutchinson Cancer Research Center (Fred Hutch) IRB in accordance with the U.S. Department of Health and Human Services regulations at 45 CFR 46 (approval number: IR# 3467-EXT). Participants provided written informed consent to participate. Additional consent to review medical records was obtained through signed written consent. Fred Hutch has an approved FWA on file with the Office for Human Research Protections (OHRP) under assurance number 0001920. The trial was performed in accordance with the Declaration of Helsinki.

Consent to publish

Not applicable.

Data availability

The following data will be made available beginning 1 July 2022: the identified participant data and data dictionary (information about data sharing for the Women’s Health Initiative can be found at www.WHI.org/researchers/data/Documents/WHI%20Data%20Sharing%20Statement.pdf). For these analyses, data will be publicly available two years after the publication of this paper. The following supporting documents are available: statistical/analytical and informed consent form (https://sp.whi.org/researchers/data/Documents/WHI%20Data%20Sharing%20Statement.pdf).

Competing interests

Rowan T. Chlebowski is a consultant for Novartis, AstraZeneca, Genentech, Merck, Immunomedics, and Puma and received honorarium from Novartis and AstraZeneca. None of the other authors report any competing interests related to this study.

Funding information

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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Pan, K., Aragaki, A.K., Neuhouser, M.L. et al. Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women’s Health Initiative (WHI) randomised trial. Br J Cancer 125, 372–379 (2021). https://doi.org/10.1038/s41416-021-01379-w

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