Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative

Rowan T Chlebowski; Aaron K Aragaki; Kathy Pan; Michael S Simon; Marian L Neuhouser; Reina Haque; Thomas E Rohan; Jean Wactawski-Wende; Tonya S Orchard; Joanne E Mortimer; Dorothy Lane; Andrew M Kaunitz; Pinkal Desai; Robert A Wild; Ana Barac; JoAnn E Manson

doi:10.1002/cncr.35318

Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative

Cancer. 2024 May 13. doi: 10.1002/cncr.35318. Online ahead of print.

Authors

Rowan T Chlebowski¹, Aaron K Aragaki², Kathy Pan³, Michael S Simon⁴, Marian L Neuhouser^{2

5}, Reina Haque⁶, Thomas E Rohan⁷, Jean Wactawski-Wende⁸, Tonya S Orchard⁹, Joanne E Mortimer¹⁰, Dorothy Lane¹¹, Andrew M Kaunitz¹², Pinkal Desai¹³, Robert A Wild¹⁴, Ana Barac¹⁵, JoAnn E Manson¹⁶

Affiliations

¹ The Lundquist Institute, Torrance, California, USA.
² Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
³ Kaiser Permanente Southern California, Downey, California, USA.
⁴ Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
⁵ Department of Health Systems Science, Department of Research & Evaluation, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA.
⁶ Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA.
⁷ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
⁸ Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, USA.
⁹ Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA.
¹⁰ Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA.
¹¹ Department of Family, Population and Preventive Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York, USA.
¹² Department of Obstetrics and Gynecology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA.
¹³ Weill Cornell Medical College, New York, New York, USA.
¹⁴ College of Medicine, The University of Oklahoma, Oklahoma City, Oklahoma, USA.
¹⁵ Inova Schar Cancer Institute and Inova Schar Heart and Vascular Institute, Fairfax, Virginia, USA.
¹⁶ Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 38736319
DOI: 10.1002/cncr.35318

Abstract

Background: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials.

Methods: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status.

Results: After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m²; p < .001).

Conclusions: MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Keywords: Women's Health Initiative; breast cancer; diabetes; metabolic syndrome; obesity; waist circumference.

Abstract

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