The Impact of Progesterone Receptor Status on Survival Outcomes in Metastatic Breast Cancer Patients Treated with First-Line CDK4/6 Inhibitors

Background/Objectives: CDK4/6 inhibitors have changed the landscape of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC) management. It is essential to identify predictive and prognostic factors for the efficacy of CDK4/6 inhibitors. We aimed to investigate the differences in characteristics and outcomes of patients receiving first-line CDK4/6 inhibitors according to PgR status. Methods: This multicenter retrospective study included 351 patients treated with first-line CDK 4/6 inhibitors for HR-positive/HER2-negative metastatic BC. Patients were categorized based on their PgR expression levels, including the PgR-low (<20%) and PgR-high (≥20%) groups, and baseline characteristics, treatment responses, and survival outcomes were analyzed. Results: The median age was 57 years (range: 26–85). A total of 99 patients were premenopausal, and 252 patients were postmenopausal. There were 115 (32.8%) patients in the PgR-low group, while 236 (67.2%) were in the PgR-high group. The majority of patients (56.7%) presented with de novo metastatic disease. Visceral metastases presented in 44.2% of patients. Low PgR expression was significantly associated with lower estrogen receptor levels (p = 0.031), elevated Ki-67 levels (p = 0.002), a higher incidence of visceral metastases (p = 0.035), and recurrent disease (p = 0.019). In the multivariate analysis, low PgR expression was a significant independent predictor of worse progression-free survival (PFS) and overall survival (OS). Conclusions: We demonstrated that low PgR expression is independently and significantly correlated with shorter PFS and OS. These findings support low PgR expression as a valuable prognostic biomarker in metastatic BC patients treated with first-line CDK4/6 inhibitors.