Exploratory analysis of biomarkers associated with clinical outcomes from the study of palbociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer
Soohyeon Lee,
Kyunghee Park,
Gun Min Kim,
Kyung Hae Jung,
Seok Yun Kang,
In Hae Park,
Jee Hyun Kim,
Hee Kyung Ahn,
Woong-Yang Park,
Seock-Ah Im,
Yeon Hee Park
Affiliations
Soohyeon Lee
Division of Oncology-Hematology, Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul, South Korea
Kyunghee Park
Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea
Gun Min Kim
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
Kyung Hae Jung
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Seok Yun Kang
Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea
In Hae Park
Department of Medical Oncology, Korea University College of Medicine, Korea University Guro Hospital, Seoul, South Korea
Jee Hyun Kim
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
Hee Kyung Ahn
Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea
Woong-Yang Park
Samsung Genome Institute, Samsung Medical Center, Seoul, South Korea
Seock-Ah Im
Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, College of Medicine, Seoul, South Korea; Corresponding author. Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, College of Medicine, 101, Daehak-ro, Jongro-gu, Seoul, 03080, South Korea.
Yeon Hee Park
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Corresponding author. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
Background: Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase ll trial comparing palbociclib + ET versus capecitabine in premenopausal women with hormone receptor positive, HER2 negative metastatic breast cancer (MBC). This exploratory analysis investigated potential biomarkers of palbociclib plus ET on PFS. Patients and methods: Of 178 patients randomized (92 palbociclib plus ET; 86 capecitabine), we performed targeted sequencing (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response on PFS. Hazard ratios (HRs) were estimated using unstratified Cox proportional hazards models. Results: PIK3CA (41%) and TP53 (33%) mutations and CCND1 copy number variation (29%) were found most frequently in targeted sequencing of 141 patients. ESR1 mutations were found only in 3.5% of patients of this population. Luminal type showed better prognosis in palbociclib + ET arm but no impact on PFS difference in capecitabine arm. High TMB, TP53 mutation, PTEN loss of function mutation and RB1 pathway alteration showed worse prognosis in palbociclib plus ET arm. Patients with BRCA2 pathogenic mutations showed worse prognosis regardless of PAM50 subtypes. AURKA mutation/amplification, BRIP1/MYC/RAD51C amplification were significantly associated to the patients with short PFS <6 month. Conclusion: Of palbociclib plus ET, luminal type showed better prognosis and BRCA2 pathogenic mutation showed worse prognosis regardless luminal/non-luminal type. Further exploration of molecular variables is warranted to determine and validate biomarkers of efficacy and resistance.
