Germline genome-wide association studies in women receiving neoadjuvant chemotherapy with or without bevacizumab

Pharmacogenetics and Genomics
James N IngleRichard M Weinshilboum

Abstract

Neoadjuvant chemotherapy (NAC) for breast cancer is widely utilized, and we performed genome-wide association studies (GWAS) to determine whether germ-line genetic variability was associated with benefit in terms of pathological complete response (pCR), disease-free survival, and overall survival in patients entered on the NSABP B-40 NAC trial, wherein patients were randomized to receive, or not, bevacizumab in addition to chemotherapy. Patient DNA samples were genotyped with the Illumina OmniExpress BeadChip. Replication was attempted with genotyping data from 1398 HER2-negative patients entered on the GeparQuinto NAC study in which patients were also randomized to receive, or not, bevacizumab in addition to chemotherapy. A total of 920 women from B-40 were analyzed, and 237 patients achieved a pCR. GWAS with three phenotypes (pCR, disease-free survival, overall survival) revealed no single nucleotide polymorphisms (SNPs) that were genome-wide significant (i.e. P≤5E-08) signals; P values for top SNPs were 2.04E-07, 5.61E-08, and 5.63E-08, respectively, and these SNPs were not significant in the GeparQuinto data. An ad-hoc GWAS was performed in the patients randomized to bevacizumab (457 patients with 128 pCR) who showed signal...Continue Reading

References

Jan 3, 1991·The New England Journal of Medicine·N WeidnerJ Folkman
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
Dec 28, 2007·The New England Journal of Medicine·Kathy MillerNancy E Davidson
Jan 27, 2012·The New England Journal of Medicine·Gunter von MinckwitzUNKNOWN Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups
Jan 27, 2012·The New England Journal of Medicine·Harry D BearNorman Wolmark
Sep 17, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G von MinckwitzUNKNOWN GBG/AGO-B study groups
May 6, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A S CoatesUNKNOWN Panel Members
Oct 17, 2017·Molecular Metabolism·Colin J PalmerAlexander S Banks

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Citations

Sep 17, 2021·International Journal of Cancer. Journal International Du Cancer·Julia C F QuintanilhaFederico Innocenti

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