Association of Different Metabolic Obesity Phenotypes with Breast Cancer Risk in Women: a Prospective Cohort Study

Abstract

Background Earlier studies have investigated the association between overweight/obesity and an elevated risk of breast cancer in women. However, some studies have found that it may not be scientifically accurate to solely analyze the association between overweight/obesity and breast cancer in women for overweight/obesity can be classified into different metabolic phenotypes. The current findings on the association of different metabolic phenotypes with breast cancer remain inconsistent. Objective To prospectively analyze the associations of different metabolic obesity phenotypes with the risk of breast cancer in women. Methods In this prospective cohort study, female employees (n=23 406) of Kailuan Group who participated in physical examinations for the first time in Kailuan General Hospital and its 11 affiliated hospitals from 2006 to 2008 were selected as the study subjects and received questionnaire investigation, physical examination and laboratory tests. The study subjects were divided into the four groups based on the types of metabolic syndrome and BMI, including metabolically healthy normal weight (MHNW) group (n=12 739), metabolically unhealthy normal weight (MUNW) group (n=1 060), metabolically healthy overweight/obese (MHO) group (n=6 394), and metabolically unhealthy overweight/obese (MUO) group (n=3 213). The subjects were followed up, with the first physical examination attended as the starting point, and new onset breast cancer, death, or the end of follow-up time (2020-12-31) as the endpoints. Multivariate Cox proportional hazard regression model was used to estimate the association of the four groups with the risk of breast cancer. Results During an average follow-up of (13.26±1.85) years, with 353 new cases of breast cancer and an incidence density of 11.38 cases per 10 000 person-years in the total population. The incidence cases in the MHNW, MUNW, MHO, and MUO groups were 154, 21, 113, and 65, respectively, with the incidence density of 9.08, 15.37, 13.27, and 15.49 per 10 000 person-years, and the cumulative incidence of 1.22%, 2.01%, 1.67%, and 1.93%, respectively. Multivariate Cox proportional hazard regression model analysis, after adjusting for confounders, showed that compared with the MHNW group, the risk of breast cancer was increased by 42% (HR=1.42, 95%CI=1.11-1.82) and 59% (HR=1.59, 95%CI=1.17-2.17) in the MHO group and MUO group, respectively. Stratified analysis by menopausal status showed that compared to the MHNW group, the MUO group was associated with a 69% increase in risk of premenopausal breast cancer (HR=1.69, 95%CI=1.01-2.83). The risk of postmenopausal breast cancer was increased by 85% (HR=1.85, 95%CI=1.09-3.14), 50% (HR=1.50, 95%CI=1.06-2.13), and 55% (HR=1.55, 95%CI=1.05-2.28) for the MUNW, MHO, and MUO groups, respectively, compared to the MHNW group. Conclusion Overweight/obesity is a risk factor for female breast cancer, and overweight/obesity with metabolic abnormalities further increases the risk of breast cancer. Additionally, normal weight postmenopausal women who are metabolically unhealthy may be at an increased risk of postmenopausal breast cancer.

Keywords

• breast neoplasms|obesity|metabolic syndrome|cohort studies|prospective studies|root cause analysis