Does obesity and metabolic syndrome affect a woman's risk of breast cancer? Study sheds light

In the Women's Health Initiative (WHI) randomized trial, adopting a low-fat diet was found to decrease breast cancer mortality, particularly among women with multiple metabolic syndrome components such as obesity, high blood pressure, elevated blood sugar, and abnormal cholesterol levels.

The analysis, published in the journal Cancer, indicated that metabolic syndrome and obesity each have different associations with breast cancer subtypes and mortality risk.

Obesity is a prevalent health concern among women worldwide, with its incidence steadily rising in recent years. Alongside its association with various metabolic disorders, including type 2 diabetes and cardiovascular disease, obesity has also been closely linked to an increased risk of cancer. In particular, obese women face a heightened likelihood of developing breast cancer, among other malignancies, due to the complex interplay of hormonal imbalances, chronic inflammation, and metabolic dysregulation associated with excess adiposity.

Metabolic syndrome, characterized by a cluster of metabolic abnormalities including hypertension and hyperglycemia, poses a significant risk factor for cancer-related deaths in women. This syndrome contributes to a systemic environment conducive to tumor growth and progression. Insulin resistance, a hallmark feature of metabolic syndrome, leads to elevated levels of insulin and insulin-like growth factor 1 (IGF-1), both of which promote cell proliferation and inhibit apoptosis, thereby fostering the development and spread of cancer cells.

In the study, researchers analyzed data from 63,330 postmenopausal participants of the WHI clinical trial who had no history of breast cancer, along with normal entry mammograms and MetS scores ranging from 0 to 4. Following a median follow-up period of 23.2 years, the analysis revealed 4,562 new cases of breast cancer and 659 deaths attributed to breast cancer (breast cancer mortality).

The study found that a higher metabolic syndrome score, regardless of obesity, was linked to poorer prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative breast cancers, and a 44% higher risk of breast cancer mortality. Obesity, irrespective of the metabolic syndrome score, was associated with better prognosis, ER-positive, and PR-positive cancers. Only women with severe obesity faced a higher risk of breast cancer mortality.

Reference: Rowan T. Chlebowski MD, PhD, Aaron K. Aragaki MS, Kathy Pan MD, Michael S. Simon MD, MPH, et al.; Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women’s Health Initiative; CANCER; https://doi.org/10.1002/cncr.35318