TOPLINE:
Postmenopausal women with higher metabolic syndrome scores, regardless of obesity, were more likely to be diagnosed with breast cancers with poor prognoses, while those with obesity, regardless of metabolic syndrome, had a higher overall incidence of breast cancer, but these were more likely to be good-prognosis cancers, new data from the Women’s Health Initiative (WHI) suggested.
METHODOLOGY:
Both metabolic syndrome and obesity are associated with dysregulated cellular metabolism, but their relative contributions to breast cancer outcomes are not well defined.The new analysis included 63,330 postmenopausal WHI study participants without prior breast cancer who had normal entry mammograms and metabolic syndrome scores.Metabolic syndrome scores of 0, 1-2, or 3-4 were based on high waist circumference, high blood pressure, high cholesterol, and diabetes history.Researchers assessed breast cancer incidence, breast cancer mortality, and death after breast cancer, evaluating the relative contributions of metabolic syndrome scores and obesity over> 20 years of follow-up.Over the follow-up period, researchers reported 4562 incident breast cancers; among those diagnosed with breast cancer, there were 659 deaths from breast cancer and 2073 deaths after breast cancer.
TAKEAWAY:
Having a higher metabolic syndrome score (3-4 vs 0), adjusted for body mass index (BMI), was significantly associated with more poor-prognosis breast cancers — specifically estrogen receptor (ER)–positive, progesterone receptor (PR)–negative cancers (hazard ratio [HR], 1.47); however, a higher metabolic syndrome score was not associated with a significantly higher incidence of breast cancer overall.Having a higher metabolic syndrome score (3-4 vs 0) was significantly associated with a higher risk of dying from breast cancer (HR, 1.44) and a higher risk for death after breast cancer (HR, 1.53).Obesity, adjusted for metabolic syndrome score, was significantly associated with a higher incidence of breast cancers overall, with the risk increasing as BMI increased. These cancers, however, were more likely to be good-prognosis cancers — specifically ER-positive, PR-positive disease; obesity was not associated with more poor-prognosis cancers.Breast cancer mortality was only significantly higher among women with severe obesity (BMI ≥ 35), though obesity was associated with more deaths after breast cancer.
IN PRACTICE:
Metabolic syndrome and obesity “represent separate targets for breast cancer prediction and prevention strategies,” the researchers wrote. “Targeting obesity alone will have a greater effect on breast cancer incidence than breast cancer mortality. Targeting [metabolic syndrome] score will have a greater effect on breast cancer mortality by identifying women at increased risk of poor-prognosis ER-positive, PR-negative breast cancers.”
SOURCE:
The study, led by Rowan T. Chlebowski, MD, PhD, The Lundquist Institute, Torrance, California, was published online on May 13, 2024, in Cancer.
LIMITATIONS:
The study relied on self-reported data for diabetes and cholesterol history and lacked comprehensive breast cancer therapy information.
DISCLOSURES:
The study was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Chlebowski reported receiving personal fees from Novartis, AstraZeneca, Pfizer, and UpToDate; the other coauthors reported a range of disclosures.
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