Obesity and Metabolic Syndrome Factors Potentially Associated With Breast Cancer Receptor Subtypes, Mortality

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According to findings published in Cancer, a low-fat diet reduced breast cancer mortality, particularly in women with more metabolic syndrome (MetS) factors, such as obesity, high blood pressure, elevated blood sugar, and abnormal cholesterol. Additionally, the Women’s Health Initiative (WHI) analysis demonstrates that MetS and obesity each have different associations with breast cancer subtypes and mortality risk.¹

In this WHI randomized trial, the investigators included 63,330 postmenopausal women without prior breast cancer who had a normal mammogram. At the time of entry, each participant’s body mass index (BMI) and MetS score (0, 1-2, and 3,4) was determined. MetS scores considered the following: high waist circumference (≥88 cm); high blood pressure (either systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history); history of high cholesterol; and history of diabetes. The study evaluated the associations between MetS and obesity within postmenopausal breast cancer in women. Outcomes included breast cancer incidence, breast cancer mortality, deaths following breast cancer, and results by hormone receptor status.^1,2

“Postmenopausal women with higher MetS scores are a previously unrecognized population at higher breast cancer mortality risk,” said lead author Rowan T. Chlebowski, MD, PhD, The Lundquist Institute, in a press release. “Determination of MetS scores in the clinic requires only 3 questions regarding cholesterol, diabetes, and hypertension history as well as waist circumference and blood pressure measurements, which are commonly determined during routine visits.”¹

According to the findings, a higher MetS score (3-4) when adjusted for BMI was significantly associated with poorer prognoses, estrogen receptor (ER)-positive, and progesterone receptor (PR)-negative cancers (p = .03) at a mortality follow-up after 20 years. Approximately 53% more deaths after breast cancer (p < .001) and 44% higher breast cancer mortality (p = .03) were observed at follow-up. There were 4562 incident breast cancers and 659 breast cancer-related mortalities.^1,2

Additionally, obesity status when adjusted for MetS score was significantly associated with more good prognoses, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), as well as more deaths after breast cancer (p < .001). The authors observed that higher breast cancer mortality was present in women with severe obesity, with BMIs of 35 kg/m2 or higher (p < .001).²

The investigators note that MetS and obesity status have independent and differential associations with breast cancer mortality and subtypes, and that both may represent separate targets for the prediction and prevention strategies for breast cancer.²

Another study published in JAMA Network analyzed 4 WHI randomized trials to determine whether hormone therapy, supplementation with calcium and vitamin D, as well as dietary modifications in postmenopausal women would decrease the risks of different cancers (eg, colorectal, breast) and chronic diseases. The findings did not appear to suggest associations between the reduced risk of cancers and chronic diseases, however, some evidence suggested that there is a potential role of low-fat diets influencing breast cancer mortality.³

Hormone therapy—specifically conjugated equine estrogens (CEE)—in menopausal women who received a prior hysterectomy appeared to lower the rates of breast cancer compared with those who received placebo (0.28% vs 0.35%; HR, 0.79; 95% CI, 0.61-1.02); however, the study authors noted them to be “non-significant.” Additionally, a low-fat dietary pattern including an increased intake of fruits, vegetables, and grains and a 20% reduction in total fat consumption appeared to present a lower incidence of breast cancer mortality at a 20-year follow-up compared with a usual diet group (0.037% vs 0.047%; HR, 0.79; 95% CI, 0.64-0.97; P = .02).³

Although these data only suggest a potential role in a low-fat diet to reduce breast cancer mortality, and not necessarily to prevent it, the study authors still suggest that further research is conducted to assess the potential association.³

References

1. Wiley. How do obesity and metabolic syndrome affect women’s risks of breast cancer and cancer-related death? News release. May 13, 2024. Accessed May 17, 2024. https://newsroom.wiley.com/press-releases/press-release-details/2024/How-do-obesity-and-metabolic-syndrome-affect-womens-risks-of-breast-cancer-and-cancer-related-death/default.aspx

2. Chlebowski, RT, Aragaki, AK, Pan, K, et al. Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women’s Health Initiative. Cancer. 2024;1-10. doi:10.1002/cncr.35318

3. McGovern, G. Hormone Therapy, Vitamin Supplementation in Postmenopausal Women Did Not Decrease Risk of Cancer, Chronic Disease. Pharmacy Times. May 13, 2024. Accessed May 17, 2024. https://www.pharmacytimes.com/view/hormone-therapy-vitamin-supplementation-in-postmenopausal-women-did-not-decrease-risk-of-cancer-chronic-disease