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

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.