| Autor: |
Christel Fontaine, Sylvia De Brakeleer, Erik Teugels, Vincent Renard, Heidi Van den Bulk, Peter Vuylsteke, Philippe Glorieux, Catherine Dopchie, Sofie Joris, Lore Decoster, Ahmad Awada, Kevin Punie, Hans Wildiers, Jacques De Grève |
| Rok vydání: |
2022 |
| Popis: |
BackgroundBSMO 2014-01 is a published prospective phase 2 study investigating neoadjuvant weekly paclitaxel and carboplatin, followed by epirubicin and cyclophosphamide in 63 patients with triple-negative breast cancer. Pathological complete response (pCR) was observed in 54%. A secondary endpoint of the study was to correlate pCR rate to the presence of germline pathogenic variants in DNA damage response (DDR) genes or in core genes involved in Homologous Recombination (HR).MethodsPeripheral blood from 60 patients was collected for germline DNA analysis. Whole Exome Sequencing was performed; only rare variants (minor allelic frequency < 0.01) in 276 DDR genes were considered. The correlation between pCR rate and DDR or HR deficiency was analyzed using the Fisher's exact test. The same was done for the correlation between DDR gene mutations and the presence of hematologic toxicities. ResultsThirty-five out of 60 patients (58.3%) carried a protein disrupting germline mutation in a DDR gene. Twenty-four of these 35 patients (68.6%) had a pCR, while a pCR was observed in 40% without a DDR mutation (p=0.026). In 14/15 patients (93.3%) with a HR core gene mutation a pCR was obtained, while a pCR was present in 44.4% without a HR core gene mutation (p=0.0007). Eight of nine patients (88.9%) with a BRCA1 or BRCA2 pathogenic variant reached a pCR compared to 51% of the BRCA wild-type patients (p=0.035). ConclusionsThis is the first study to demonstrate that germline pathogenic variants in genes involved in HR core genes predicts for pCR after platinum-containing neoadjuvant chemotherapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
