期刊
BREAST
卷 62, 期 -, 页码 52-60出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.breast.2022.01.014
关键词
Palbociclib; Next-generation sequencing; Progression-free survival; Biomarker
资金
- South Korean Ministry of Health and Welfare [HA17C0055]
- South Korean National R&D Program for Cancer Control, Ministry of Health and Welfare [1720150]
- Korea Health Promotion Institute [1720150] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
This article investigated the treatment effect of Palbociclib plus endocrine therapy in metastatic breast cancer patients and explored potential biomarkers associated with treatment response and prognosis. The study found that genomic alterations in patients were correlated with treatment response and prognosis. Patients with luminal type showed better prognosis in the Palbociclib plus endocrine therapy arm, while BRCA2 pathogenic mutation was associated with worse prognosis.
Background: Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase II 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. (C) 2022 The Authors. Published by Elsevier Ltd.
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