Effect of body mass index on the prognostic impact of progesterone receptor in postmenopausal ER+HER2- breast cancer: A nationwide study in Korean Breast Cancer Society and multi-institutional cohort.

Abstract

e12541 Background: Obesity, a known risk factor for breast cancer, is associated with increased estrogen levels in postmenopausal women, which can stimulate progesterone receptor (PgR) expression. This study aimed to investigate how body mass index (BMI) influences PgR expression and its prognostic impact in postmenopausal ER+/HER2- breast cancer. Methods: We analyzed data from two large-scale cohorts: the Korean Breast Cancer Registry (KBCR) and a multi-institutional registry. Patients were postmenopausal women with ER+/HER2- breast cancer diagnosed between January 1991 and December 2019. BMI was categorized as <25 kg/m² (normal weight) and ≥25 kg/m² (overweight/obese). PgR status was determined by immunohistochemistry. The primary endpoint was 6-year oncologic outcome. Results: In both cohorts, a higher proportion of overweight/obese patients were PgR-positive. Multivariate analysis revealed that PgR-negative status was significantly associated with worse 6-year overall survival in overweight/obese patients (KBCR: HR 1.45, 95% CI 1.06-1.97, P=0.018) but not in normal-weight patients (KBCR: HR 1.15, 95% CI 0.85-1.56, P=0.366). Similarly, in the multi-center cohort, PgR-negative status was associated with worse 6-year recurrence-free survival (RFS) only in overweight/obese patients (HR 2.93, 95% CI 1.29-6.69, P=0.011). No significant association was observed between PgR status and 6-year RFS in normal-weight patients. Mean of 21-gene recurrence score was significantly higher in the PgR-negative group than in the PgR-positive group, regardless of BMI. Conclusions: Our findings suggest that the prognostic impact of PgR expression is significantly modified by BMI in postmenopausal ER+/HER2- breast cancer. PgR-negative status is a strong predictor of poor outcomes in overweight/obese patients, while its prognostic significance is diminished in normal weight patients, potentially reflecting the influence of host factors beyond tumor biology.