Body mass index and progesterone receptor in postmenopausal ER-positive/HER2-negative breast cancer: A nation-wide study in Korean breast cancer society and the multi-institutional cohort

Background: Obesity is a risk factor for breast cancer and associated with increased estrogen levels that stimulate the progesterone receptor (PgR). Understanding interplay between obesity, PgR, and prognosis in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (ER+/HER2-) is crucial. This study aimed to investigate the association between body mass index (BMI) and the prognostic value of PgR. Methods: Study included 10,125 postmenopausal patients with ER+/HER2-breast cancer between January 1991 to December 2019. Patients were categorized according to BMI (cutoff: 25 kg/m²) and PgR (positive/negative). The primary outcomes were the 6-year overall survival (OS) in the Korean Breast Cancer Registry (KBCR) cohort and 6-year recurrence-free survival (RFS) in the multi-institutional cohort. Results: In both cohorts, a greater proportion of patients with high BMI were PgR-positive, and the mean BMI was higher in the PgR-positive group. PgR-negativity was associated with worse 6-year OS in the KBCR cohort among patients with BMI ≥25 kg/m² (hazard ratio [HR], 1.45; 95 % confidence intervals [CI], 1.06–1.97; P = .02), but not in those with BMI <25 kg/m². Similarly, in the multi-institutional cohort, PgR-negativity was associated with worse 6-year RFS only in patients with BMI ≥25 kg/m² (HR, 2.93; 95 % CI, 1.29–6.69; P = .01). The mean 21-gene recurrence score was higher in the PgR-negative group, regardless of the BMI. Conclusions: In postmenopausal patients with ER+/HER2-breast cancer, the prognostic impact of PgR is modified by BMI. PgR-negativity is a strong predictor of poor outcomes in obese patients but not in non-obese patients.