Multiple gene aberrations and breast cancer: lessons from super-responders

BMC Cancer

Case Report

Razelle Kurzrock¹  Stacy L. Moulder²  Filip Janku³  Johnique T. Atkins³  Jennifer J. Wheler³  Philip J. Stephens⁴  Roman Yelensky⁴ 

[1] Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California at San Diego Moores Cancer Center, La Jolla, CA, USA;Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Box 0455, 1400 Holcombe Boulevard, 77030, Houston, TX, USA;Foundation Medicine, Cambridge, MA, USA;

关键词: Breast cancer;    Genomic aberrations;    Next generation sequencing;   

DOI  :  10.1186/s12885-015-1439-y

 received in 2014-05-22, accepted in 2015-05-14,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Wheler et al.; licensee BioMed Central. 2015