228PD - BRAF genomic alterations in breast cancer

Date 09 October 2016
Event ESMO 2016 Congress
Session Breast cancer, metastatic
Topics Breast Cancer
Presenter Joan Albanell
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors J. Albanell1, J.A. Elvin2, J. Suh2, J. Vergilio2, I. Phuong Le3, V. Kaklamani3, S. Ali2, V. Miller4, P. Stephens5, L.M. Gay2, J.S. Ross6
  • 1Cancer Research Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 - Barcelona/ES
  • 2Pathology, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 3Health Science Center, University of Texas Health Science Center San Antonio, San Antonio/US
  • 4Clinical Development, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 5Clinical Genomics, Foundation Medicine, Inc., 02141 - Cambridge/US
  • 6Pathology, Albany Medical Center, 12208 - Albany/US



Targeting BRAF genomic alterations (GA) in non-melanoma cancer patients is well-established, but BRAF targeting for treating metastatic breast cancer (mBC) remains under investigation.


DNA was extracted from 40 microns of FFPE sections of 7850 tumors, and comprehensive genomic profiling (CGP) was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 579X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (sub), indels, copy number alterations (CNA) and fusions/rearrangements.


A total of 83 (1.1%) cases of BRAF-altered BC were identified. The mean age of the 83 patients was 57 years (range 32 to 84 years). The primary tumor was used for CGP in 29 (34.9%) cases and from metastatic sites including lymph nodes, liver, bone, lung, brain adrenal and soft tissue in 54 (65.1%). Of these 83 tumors, there were 39 ductal, 1 inflammatory, 3 metaplastic, 2 lobular and 38 NOS mBC. BRAF GA that may lead to aberrant MAPK signaling included amplifications (51.8%), V600E sub (15.7%), K601E sub (3.6%), other missense sub (21.6%), and fusions (6.0%); 3 additional mutations are uncharacterized for their effect on BRAF signaling activity (3.6%). The identified fusions were KIAA1549-BRAF (2), AGK-BRAF (1), FCHSD2-BRAF (1), and KLHDC10-BRAF (1). There was a statistically significant reduction in ERBB2 mutations in tumors harboring a BRAF GA (amplification or sub)(p = 0.011). Of the cases harboring BRAF GA, 38.6% were TNBC, 21.7% HR + /HER2-, 2.4% HR-/HER2 + , 2.4% HR + /HER2 + , and 30.1% status unknown. Targetable genes more commonly amplified in tumors with BRAF GA, compared to BRAF WT breast cancer, include CDK6 (p = 0.001), HGF (p 


BRAF GA are uncommon in BC, identified in 1.1% of cases, but include targetable base substitutions and rare fusions. BRAF GA in mBC appear to be more common in HER2-negative and TNBC mBC, and there is a significant decrease in ERBB2 mutation in tumors with BRAF GA. Targetable genes co-altered with BRAF in BC include CDK6, HGF and MET. Further study of BRAF alterations in BC appears warranted.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine, Inc.


Foundation Medicine, Inc.


J.A. Elvin, J. Suh, J-A. Vergilio, S. Ali, V. Miller, P. Stephens, L.M. Gay, J.S. Ross: Employee of and stockholder in Foundation Medicine, Inc. All other authors have declared no conflicts of interest.