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BMC Cancer

, 15:442

Genetics, genomics and epigenetics


BackgroundThe presence of multiple molecular aberrations in patients with breast cancer may correlate with worse outcomes.

Case PresentationsWe performed in-depth molecular analysis of patients with estrogen receptor-positive, HER2-negative, hormone therapy-refractory breast cancer, who achieved partial or complete responses when treated with anastrozole and everolimus. Tumors were analyzed using a targeted next generation sequencing NGS assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. Patients received anastrozole 1 mg PO daily and everolimus 5 or 10 mg PO daily. Thirty-two patients with breast cancer were treated on study and 5 16 % achieved a partial or complete response. Primary breast tissue was available for NGS testing in three of the responders partial response with progression free survival of 11 and 14 months, respectively; complete response with progression free survival of 9+ months. The following molecular aberrations were observed: PTEN loss by immunohistochemistry, CCDN1 and FGFR1 amplifications, and PRKDC re-arrangement NGS patient #1; PIK3CA and PIK3R1 mutations, and CCDN1, FGFR1, MYC amplifications patient #2; TP53 mutation, CCNE1, IRS2 and MCL1 amplifications patient #3. Some but not all of these aberrations converge on the PI3K-AKT-mTOR pathway, perhaps accounting for response.

ConclusionsPatients with estrogen receptor-positive breast cancer can achieve significant responses on a combination of anastrozole and everolimus, even in the presence of multiple molecular aberrations. Further study of next generation sequencing-profiled tumors for convergence and resistance pathways is warranted.

KeywordsBreast cancer Genomic aberrations Next generation sequencing Electronic supplementary materialThe online version of this article doi:10.1186-s12885-015-1439-y contains supplementary material, which is available to authorized users.

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Autor: Jennifer J. Wheler - Johnique T. Atkins - Filip Janku - Stacy L. Moulder - Roman Yelensky - Philip J. Stephens - Razelle


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