Palbociclib in endocrine-resistant metastatic breast cancer patients: gene polymorphism- based study.

BACKGROUND: Despite the proven benefit of adding palbociclib to endocrine therapy (ET) as demonstrated in pivotal clinical trials (e.g., PALOMA-2 and PALOMA-3), many patients with hormone receptor-positive (HR+) and human epidermal growth factor-2-negative (HER2−) metastatic breast cancer (MBC) still experience early disease progression. This study aimed to identify predictive biomarkers for long-term response and evaluate the impact of adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) gene polymorphisms in MBC patients who had progressed on prior ET. METHODS: This prospective cohort study included 95 adult MBC patients treated with palbociclib. Demographic, laboratory, and therapeutic variables were analyzed. A genotyping assay was done using real-time polymerase chain reaction (RT-PCR). RESULTS: Low Ki-67 expression (< 20%) and moderate-to-severe (grade 3/4) neutropenia were associated with longer progression-free survival (PFS) (p = 0.00 and p = 0.01, respectively). Regarding adverse effects, patients carrying the minor-T-allele (CT/TT) had a lower incidence of neutropenia compared to those with the CC genotype (33.3% vs. 66.7%, p = 0.03). Patients with a baseline absolute neutrophil count (ANC) < 3.6 × 10³/mm³ had higher rates of grade 3/4 neutropenia and dose interruptions/reductions (p = 0.00). In univariate logistic regression analysis, homozygous carriers of the ABCB1 CC genotype had a higher risk of grade 3/4 neutropenia (Odds ratio (OR) = 0.333, 95% confidence interval (CI) [0.121–0.920]; p = 0.03). CONCLUSION: Ki-67 expression and grade 3/4 neutropenia were associated with PFS in MBC, suggesting their potential relevance to clinical outcomes. Additionally, pharmacogenetic polymorphisms may help explain interindividual variations in treatment safety.