[Association between functional status-based obesity classification and breast cancer risk: a prospective cohort...

Objective: To investigate the association between different functional status-based obesity classifications and the risk of breast cancer in women. Methods: Based on the prospective Kailuan cohort in China, this study included 19 921 female employees who first participated in the Kailuan health examination in 2006. According to the functional status-based obesity criteria proposed by the Lancet Commission on Clinical Obesity, participants were divided into the non-obesity group (n=9 366), preclinical obesity group (n=5 061), and clinical obesity group (n=5 494). The Kaplan-Meier analysis and the Log-rank test were used to compare the cumulative incidence of breast cancer among the groups. Cox regression models were employed to evaluate the associations between different functional status-based obesity classifications and breast cancer risk, with stratified analyses by age and menopausal status. Results: By the end of follow-up on December 31, 2023, a total of 379 incident breast cancer cases were confirmed, with a median follow-up of 16.95 years. The numbers of new breast cancer cases in the non-obesity, preclinical obesity, and clinical obesity groups were 144, 105 and 130, respectively, with cumulative incidence rates of 0.93%, 1.26%, and 1.49%, respectively (χ²=15.73, P＜0.001). In the multivariable Cox regression model adjusted for age, lifestyle factors, family history, and medication use, using the non-obesity group as the reference, the risks of breast cancer were progressively higher in the preclinical obesity group (HR=1.32, 95% CI: 1.02-1.71) and the clinical obesity group (HR=1.60, 95% CI: 1.22-2.09). After adding a multiplicative interaction term between obesity classification and age to the multivariable Cox regression model, a significant interaction was observed between obesity status and age (χ²=7.22, P=0.027). In age-stratified analyses, among women aged ≤50 years, both the preclinical obesity group and the clinical obesity group showed increased risk of breast cancer (HR=1.52 and 2.06, respectively; both P＜0.05), whereas no significant associations were observed in women aged >50 years. The interaction between obesity phenotype and menopausal status was not statistically significant (χ²=5.38, P=0.068); however, among premenopausal women, the clinical obesity group had an increased risk of breast cancer (HR=1.67, 95% CI: 1.11-2.52). In a sensitivity analysis excluding cases diagnosed within 2 years of follow-up (n=78), the clinical obesity group remained an increased risk of breast cancer (HR=1.59, 95% CI: 1.20-2.10), while the association for the preclinical obesity group was no longer statistically significant (HR=1.23, 95% CI: 0.94-1.61). Conclusions: Both preclinical obesity and clinical obesity increase the risk of breast cancer in women, suggesting that the carcinogenic effect of obesity on breast cancer may be dependent on functional status. The association is more pronounced in women aged ≤50 years. The identification and intervention of preclinical obesity may provide a novel window of opportunity for primary prevention of breast cancer.