Frequent LOH of CYP2D6 in ER+ breast cancer determined by next-generation sequencing (NGS).

534 Background: The role of CYP2D6 genetic variation in predicting response to tamoxifen in ER+ breast cancer is a subject of ongoing debate. There has been great variability in approaches to both genotyping and phenotyping, and in particular many investigators have extracted DNA from breast cancer samples rather than peripheral blood. We hypothesized that CYP2D6 gene copy number alterations are common in ER+ breast cancer, affecting genotype results, and used NGS to characterize CYP2D6 in patients with ER+ disease. Methods: CYP2D6 sequencing was performed as part of a comprehensive NGS profile of cancer-related genes for 261 predominantly relapsed and metastatic ER+ breast cancer FFPE specimens. Sequence data were resolved into genotypes according to the * allele nomenclature. Tumor LOH was determined at CYP2D6, and its error impact on genotyping methods was estimated. To assess biological significance, the prevalence of CYP2D6 alleles and LOH in ER+ disease was compared against a control set of 99 ER- t...