Germline mutations in DNA repair genes may predict neoadjuvant therapy response in triple negative breast patients

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• 作者：Laura Spugnesi ; Michele Gabriele ; Rosa Scarpitta ; Mariella Tancredi ; Luisa Maresca ; Gaetana Gambino ; Anita Collavoli ; Paolo Aretini ; Ilaria Bertolini ; Barbara Salvadori ; Elisabetta Landucci ; Andrea Fontana ; Elena Rossetti ; Manuela Roncella ; Giuseppe Antonio Naccarato and Maria Adelaide Caligo
• 刊名：Genes, Chromosomes and Cancer
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：55
• 期：12
• 页码：915-924
• 全文大小：181K
• ISSN：1098-2264

文摘

Triple negative breast cancers (TNBCs) represent about 15–20% of all breast cancer cases and are characterized by a complex molecular heterogeneity. Some TNBCs exhibit clinical and pathological properties similar to BRCA-mutated tumors, without actually bearing a mutation in m>BRCAm> genes. This “BRCAness” phenotype may be explained by germline mutations in other genes involved in DNA repair. Although respond to chemotherapy with alkylating agents, they have a high risk of recurrence and progression. Some studies have shown the efficacy of neoadjuvant therapy in TNBC patients with DNA repair defects, but proper biomarkers of DNA repair deficiency are still needed. Here, we investigated if mutations in DNA repair genes may be correlated with anthracyclines/taxanes neoadjuvant therapy response. DNA from 19 TNBC patients undergoing neoadjuvant therapy were subjected to next generation sequencing of a panel of 24 genes in DNA repair and breast cancer predisposition. In this study, 5 of 19 patients (26%) carried a pathogenic mutation in m>BRCA1, PALB2, RAD51Cm> and two patients carried a probable pathogenic missense variant. Moreover, VUS (Variants of Unknown Significance) in other genes, predicted to be deleterious by m>in silicom> tools, were detected in five patients. Germline mutations in DNA repair genes were found to be associated with the group of TNBC patients who responded to therapy. We conclude that a subgroup of TNBC patients have defects in DNA repair genes, other than BRCA1, and such patients respond favourably to neoadjuvant anthracyclines/taxanes therapy.