Breast (Edinburgh, Scotland) · 2026
BRCA1/2, PALB2 mutations and first-line CDK4/6 inhibitor efficacy in HR+ metastatic breast cancer.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Guinel Timothé, Lusque Amélie, Mailliez Audrey, Massard Vincent, Jacot William, Guiu Severine, de la Motte Rouge Thibault, Brain Etienne, Desmoulins Isabelle, Arnedos Monica, Bailleux Caroline, Goncalves Anthony, Levy Christelle, Bachelot Thomas, Bosquet Lise, Delaloge Suzette, Frénel Jean-Sébastien
Аннотация
OBJECTIVE: To evaluate outcomes of first-line ET + CDK4/6i for HR+/HER2 metastatic breast cancer (MBC) based on BRCA/PALB2 mutations status known at treatment initiation.
METHODS AND PATIENTS: This cohort study included patients from 18 French comprehensive cancer centers treated with first-line ET and CDK4/6i between August 1, 2013, and December 31, 2023. Multivariable models including a Cox proportional hazard with a time-varying approach and landmark analyses at different timepoints (at the initiation of the first-line therapy and at 6 months after the initiation of the first line) assessed the association between germline and/or somatic BRCA and PALB2 genes alteration (categorized as "BRCA/PALB2m" (mutated) "BRCA/PALB2wt" (wild type), and "untested"), with progression-free (PFS) and overall survival (OS).
RESULTS: Among 4283 eligible patients, baseline status was categorized as BRCA/PALB2m in 80 patients (1.9%), BRCA/PALB2wt in 467 patients (10.9%), and untested in 3736 patients (87.2%). Median follow-up was 43.7 months [95%CI, 42.6-44.9]. Median PFS was significantly shorter in BRCA/PALB2m patients (9.9 months [7.6-13.0]) compared to BRCA/PALB2wt (15.4 months [13.9-17.3]) and untested patients (18.3 months [17.6-19.3]). In the multivariable analysis ((including age, number of metastatic sites, presence of visceral metastases, de novo status, and tumor grade), BRCA/PALB2m carriers had a shorter PFS compared to BRCA/PALB2wt (adjusted HR [95% CI] 1.61 [1.24-2.09]; p < 0.001). Time-varying approach, landmark analysis at 6-months and propensity score matching analysis showed consistent results.
CONCLUSIONS AND RELEVANCE: In this cohort, using a careful methodology, BRCA1/2 and PALB2 mutation carriers had reduced PFS with first-line ET + CDK4/6i compared to wild-type patients.
METHODS AND PATIENTS: This cohort study included patients from 18 French comprehensive cancer centers treated with first-line ET and CDK4/6i between August 1, 2013, and December 31, 2023. Multivariable models including a Cox proportional hazard with a time-varying approach and landmark analyses at different timepoints (at the initiation of the first-line therapy and at 6 months after the initiation of the first line) assessed the association between germline and/or somatic BRCA and PALB2 genes alteration (categorized as "BRCA/PALB2m" (mutated) "BRCA/PALB2wt" (wild type), and "untested"), with progression-free (PFS) and overall survival (OS).
RESULTS: Among 4283 eligible patients, baseline status was categorized as BRCA/PALB2m in 80 patients (1.9%), BRCA/PALB2wt in 467 patients (10.9%), and untested in 3736 patients (87.2%). Median follow-up was 43.7 months [95%CI, 42.6-44.9]. Median PFS was significantly shorter in BRCA/PALB2m patients (9.9 months [7.6-13.0]) compared to BRCA/PALB2wt (15.4 months [13.9-17.3]) and untested patients (18.3 months [17.6-19.3]). In the multivariable analysis ((including age, number of metastatic sites, presence of visceral metastases, de novo status, and tumor grade), BRCA/PALB2m carriers had a shorter PFS compared to BRCA/PALB2wt (adjusted HR [95% CI] 1.61 [1.24-2.09]; p < 0.001). Time-varying approach, landmark analysis at 6-months and propensity score matching analysis showed consistent results.
CONCLUSIONS AND RELEVANCE: In this cohort, using a careful methodology, BRCA1/2 and PALB2 mutation carriers had reduced PFS with first-line ET + CDK4/6i compared to wild-type patients.