Abstract PS1-11-19: Predictive value of Progesterone Receptor expression in Advanced Breast Cancer. Systematic Review and Meta-analysis

Abstract Introduction and objectives: Endocrine therapy (ET) is the standard treatment for patients with luminal (HR+/HER2−) metastatic breast cancer (MBC). However, the predictive value of progesterone receptor (PR) expression in this setting remains controversial. This study aimed to evaluate PR expression as a predictive biomarker of progression-free survival (PFS) in patients with luminal MBC treated with ET. Materials and methods: A systematic search was conducted in PubMed, MEDLINE, and EMBASE to identify clinical trials (CTs) that included patients with luminal MBC treated with ET (either as monotherapy or in combination) and reported PR status. Data were analyzed using STATA v.12. A meta-analysis of proportions was performed to estimate pooled PR prevalence, and weighted means and frequencies were calculated. PFS according to PR status was the primary outcome. Results: Following the screening of 1,144 studies, 46 clinical trials (published between 1997 and 2024) met the eligibility criteria. Trial characteristics: phase II (40%) or phase III (48.9%); randomized design (71.7%); evaluated endocrine therapy (ET) either as monotherapy with parenteral SERDs (34.8%), or in combination with CDK4/6 inhibitors (39.1%) or PIK3CA/AKT/mTOR pathway inhibitors (26.1%). None of the trials investigating oral SERDs (N=31) reported PR status and were excluded from the meta-analysis. Patient characteristics (N=16,921): predominantly women (99.8%); median age 63 years (range 23-98); postmenopausal (52.2%) or premenopausal (10.9%); majority from Western countries (80%); visceral metastases in 48.2%, and bone-only disease in 19.1%; prior lines of therapy: none (23.9%) or ≤1 (28.3%). Most tumors were ER-positive (93.0%) and PR-positive (72.4%). The median follow-up across trials was 18.5 months. The predictive value of PR expression for PFS was reported in 25% of ET-only trials, 50% of ET+CDK4/6 trials, and 25% of ET+PIK3CA/AKT/mTOR trials. Table 1 summarizes the main findings. A statistically significant benefit was observed in patients with both PR-positive and PR-negative tumors who received combination therapy, compared to those treated with endocrine monotherapy (either fulvestrant or aromatase inhibitors AIs). Among patients receiving ET alone, clinical benefit was observed exclusively in those with PR-positive tumors. Overall heterogeneity across and within subgroups was consistent. Conclusion: PR is an accessible and standardized biomarker that may have predictive relevance in ET-based treatment strategies. In ET monotherapy settings, clinical benefit was higher in patients with PR-positive tumors. In contrast, in combination regimens, outcomes were independent of PR status. Citation Format: A. Gottlob Pérez, N. Blaya Boluda, M. Guirao García, E. García Torralba, F. Ayala de la Peña. Predictive value of Progesterone Receptor expression in Advanced Breast Cancer. Systematic Review and Meta-analysis abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-19.