Prognostic value of estrogen receptor (ER) and progesterone receptor (PR) expression levels in <i>de novo</i> and recurrent HR+/HER2- metastatic breast cancer (MBC) patients (pts) treated with CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET): Real-world evidence.

Abstract

e13078 Background: Differences in clinical outcomes have been observed between pts with de novo (dnMBC) and recurrent metastatic breast cancer (rMBC). We investigated the prognostic value of ER and PR expression levels in primary tumors in HR+/HER2 dnMBC and rMBC treated with CDK4/6i and ET. Methods: We retrospectively analyzed clinical data of HR+/HER2- MBC pts administered palbociclib (PAL), ribociclib (RIB) or abemaciclib (ABM) combined with first- or second-line ET. Duration of CDK4/6i treatment (dCDKi), second progression free survival (PFS2), and overall survival (OS) were analyzed using R statistical software (version 4.4.1). Results: A total of 2120 patients (pts) from 16 Polish cancer centers treated between Sep 2017 and Dec 2024 were analyzed: 1120 (52.8%) and 1000 (47.2%) with rMBC and dnMBC, respectively; mean age 62±12 years, luminal A and B cancers 784 (41.8%) and 1093 (58.2%) cases, respectively. ER expression of 0-10%, 11-66%, and 67-100% was found in 36 (1.7%), 163 (7.7%), and 1921 (90.6%) cases and respective PR expression in 524 (25.0%), 510 (24.4%), and 1059 (50.6%) cases. 707 pts (33.3%) received PAL, 1008 (47.5%) RIB, and 405 (19.1%) ABM; 1273 (60%) received aromatase inhibitor and 847 (40%) fulvetrant. The median follow-up was 31.4 months. Cancer phenotype and PR expression level were prognostic in dnMBC and rMBC, whereas ER expression level only in dnMBC (Table 1). Conclusions: Our results indicate biological differences between dnMBC and rMBC that may impact treatment efficacy. These differences may be due to intrinsic or acquired resistance and support the need for repeat biopsy for rMBC. dnMBC Expression (%) dCDKi PFS2 OS ER 0-6667-100 14.4 (8.5-20.8)23.1 (19.8-25.4)p=0.004 26.4 (16.5-40.5)38.1 (36.4-42)p=0.006 33.1 (20.2-RN)52.3 (45.6-66.8)p=0.003 PR 0-1011-6667-100 16.9 (13.4-22.4)18.0 (15.1-24.3)26.4 (22.9-35.4)p&lt;0.001 29.8 (24.5-39.6)31.9 (29.2-39)43.8 (38.5-55.4)p&lt;0.001 41.2 (34.5-66.8)46.8 (41.3-NR)58.4 (47.6-85.5)p&lt;0.001 Phenotype luminal Aluminal B 28.6 (23.3-35.4)18.4 (16.1-23.0)p&lt;0.001 47 (40.5-63.5)33.1 (30.1-37.3)p&lt;0.001 64.4 (47.6-NR)44.3 (39.8-54.2)p&lt;0.001 rMBC Expression (%) dCDKi PFS2 OS ER 0-6667-100 13.9 (10.4-18.3)16.2 (14.8-18.7)p=0.23 32.7 (22.2-46.4)30.7 (28.5-33.5)p=0.66 37.2 (27.9-68.6)40.8 (38.2-47.1)p=0.5 PR 0-1011-6667-100 13.0 (9.4-15.1)16.1 (13.0-19.7)20.0 (17.2-22.9)p&lt;0.001 22.2 (19.5-28.6)35.2 (31.7-40.5)32.3 (27.8-39.6)p&lt;0.001 29.7 (24.4-37.2)47.6 (40-87.4)45.4 (38.8-68.9)p&lt;0.001 Phenotype luminal Aluminal B 19.3 (15.9-22.0)11.4 (9.4-14.1)p&lt;0.001 33.6 (29.3-40.7)22.2 (20-28.3)p&lt;0.001 47.6 (38.8-61.6)29.8 (25.4-34.4)p&lt;0.001 RN, not reached; dCDKi, PFS2, OS are in months.