Predictive Value of Progesterone Receptor in Advanced Stage Breast Cancer Patients Treated with CDK4/6 Inhibitors

Abstract Purpose: Phase III studies investigating CDK4/6 inhibitors have failed to uncover significant predictive or prognostic markers aiding clinicians in therapeutic decision-making. Given the treatment complexity, identifying patient and tumor traits is crucial for CDK4/6 inhibitor use across varied treatment approaches. In our study, we aimed to evaluate the predictive role of PgR expression levels in patients with advanced-stage ER+/HER2- breast cancer treated with CDK4/6 inhibitors. Methods: In the study, 246 patients who received a combination of CDK4/6 inhibitors and endocrine therapy as first-line treatment were evaluated retrospectively. Those with PgR levels below 20% were called low PgR expression patients, and those with 20% and above were called high PgR expression patients. These two groups were compared regarding demographic characteristics and progression-free survival (PFS). Results: The mPFS of low PgR expression patients was 23.85 (95% CI; 15.47-32.23) months, and that of high PgR expression patients was 34.66 (95% CI; 24.30-45.02) months, and this was statistically significant (p: 0.008). There was also a difference in mPFS between patients with de novo disease and those with recurrent disease at diagnosis (NE vs. 25 months, respectively; p: 0.021). Additionally, tumor PgR expression (low vs. high) and disease status (de novo vs. recurrent) were determined to be independent predictive factors. Conclusions: Our study is clinically significant as it demonstrates the impact of PgR expression levels on PFS, especially given the absence of identified biomarkers predicting which patients will benefit most from CDK4/6 inhibitor treatments. However, these positive data need to be supported by further studies.