Metabolic syndrome, obesity influence breast cancer subtype, mortality risk

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Key takeaways:

  • Higher metabolic syndrome scores appeared associated with poor-prognosis breast cancers.
  • Obesity had higher associations with good-prognosis breast cancers.

Metabolic syndrome scores and obesity appeared linked in different ways to breast cancer incidence and mortality among postmenopausal women, according to findings published in Cancer.

Women with elevated metabolic syndrome (MetS) had a higher likelihood for developing poor-prognosis, ER-positive/PR-negative cancers. In contrast, those with obesity exhibited increased odds for ER‐positive/PR‐positive cancers, generally associated with better prognosis.


Metabolic syndrome scores and obesity appeared linked in different ways to breast cancer incidence and mortality among postmenopausal women. Image: Adobe Stock

“MetS and obesity represent separate targets for breast cancer prediction and prevention strategies,” Aaron K. Aragaki, MS, senior statistical analyst at Fred Hutchinson Cancer Center, told Healio.

Background and methods

Prediction models can help identify women who have greater risk for breast cancer. Endocrine-targeted therapies can reduce incidence, but prevention of primary breast cancer has not evolved much since 1998, according to study background.

Prediction models and endocrine-targeted therapies have “largely” been successful regarding “good-prognosis, highly curable cancers,” but there remains a “need to identify factors predictive of poor-prognosis breast cancers and interventions that can target such cancers,” researchers wrote.

Results of the Women’s Health Initiative (WHI) randomized trial revealed an association between higher MetS — which includes abdominal obesity, high blood pressure, reduced high‐density cholesterol, elevated triglycerides and elevated glucose levels — and these cancers. Dietary intervention reduced incidence.

“This study was conducted to reconcile results between WHI’s randomized clinical trial of low-fat dietary pattern and breast cancer, and an observational study of obesity and breast cancer,” Aragaki said. “Specifically, the randomized clinical trial resulted in no overall reduction in breast cancer incidence, but significant reductions in poor-prognosis ER-positive/PR-negative tumors and breast cancer mortality. Moreover, the dietary intervention had a more favorable influence on women who had higher MetS scores.”

Aragaki and colleagues used data from the WHI, which enrolled postmenopausal women aged 50 to 79 years with no breast cancer history between 1993 and 1998.

The cohort — which included women who had both BMI and MetS scores at entry — consisted of 63,330 participants (84.2% white; 46.6% aged 60 to 69 years).

Researchers calculated MetS scores (0, 1 to 2, or 3 to 4) based on waist circumference, blood pressure, cholesterol and diabetes history.

Median follow-up was 18.6 years for breast cancer incidence and 20.4 years for mortality.

Results and next steps

Higher MetS scores (3 to 4 vs. 0) did not appear associated with overall breast cancer incidence. However, they were associated with ER‐positive/PR‐negative cancers (HR = 1.47; 95% CI, 1.05-2.06).

Additionally, elevated MetS scores appeared linked to breast cancer mortality (HR = 1.44; 95% CI, 1.02–2.04) and death after breast cancer diagnosis (HR = 1.53; 95% CI, 1.26–1.85).

Further analyses showed waist circumference associated with breast cancer mortality (P = .03), death after breast cancer (P = .01), and incidence of ER‐positive/PR‐negative cancers (P = .04). Diabetes appeared associated with death after breast cancer (P < .001) and ER‐positive, PR‐positive cancers (P = .002).

“Postmenopausal women with higher MetS scores are a previously unrecognized population at higher breast cancer mortality risk,” Rowan T. Chlebowski MD, PhD, investigator at Lundquist Institute and chief of the division of medical oncology and hematology at Harbor-UCLA Medical Center, said in a press release. “Determination of MetS scores in the clinic requires only three questions regarding cholesterol, diabetes and hypertension history, as well as waist circumference and blood pressure measurements, which are commonly determined during routine visits.”

Analyses adjusted for MetS score showed women with overweight or obesity had significantly higher incidence of breast cancer (P < .001). The HR increased as BMI increased, with the most elevated risks observed for those with grade 2/grade 3 obesity, defined as BMI greater than 35 kg/m2 (HR = 1.69; 95% CI, 1.52-1.89)

Risk for ER‐positive/PR‐positive breast cancer also increased as BMI increased, with the most elevated risk observed among those with grade 2/grade 3 obesity (HR = 2; 95% CI, 1.75–2.29).

Death after breast cancer occurred more frequently among women with overweight or obesity (P < .001); however, breast cancer mortality only appeared significantly elevated among women with grade 2/grade 3 obesity (P < .001).

“The WHI’s dietary intervention was similar to the Dietary Approach to Stop Hypertension [DASH] for cardiovascular disease prevention,” Aragaki said. “Both approaches call for dietary moderation with increases in fruits, vegetables and grains. DASH specifically decreased saturated [fat[, which was presumed to also be reduced by WHI’s intervention that reduced total fat. Consequently, physicians can provide a ‘dietary prescription’ [DASH] to [postmenopausal women] for the prevention of cardiovascular disease and breast cancer.”

Researchers acknowledged study limitations, included the fact it was a secondary analysis, as well as the use of questionnaires and lack of therapy information.

“The Women’s Health Initiative’s results are applicable to postmenopausal women,” Aragaki said. “The translation of these results to younger women — those under 50 years of age — is an area that requires further research. President Biden’s Fund for Women’s Health Research could potentially provide the necessary resources to explore these questions and expand our understanding of women’s health across different age groups, and lead to more comprehensive prevention strategies.”


  • Chlebowski RT, et al. Cancer. 2024;doi:10.1002/cncr.35318.
  • How do obesity and metabolic syndrome affect women’s risks of breast cancer and cancer-related death? (press release). Available at: Published May 13, 2024. Accessed May 13, 2024.

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