Impact of tissue-based genomic profiling on clinical decision making in the management of patients with metastatic breast cancer at academic centers

Breast Cancer Res Treat. 2017 Nov;166(1):179-184. doi: 10.1007/s10549-017-4415-1. Epub 2017 Jul 27.

Abstract

Background: Genomic profiling can identify targetable mutations; however, the impact of tissue-based genomic profiling on clinical decision making for patients with metastatic breast cancer has not been well characterized.

Methods: Patients with stage IV breast cancer who had undergone genomic profiling between 7/2013 and 3/2015 were identified at three academic cancer centers. Genomic analysis was determined to have impacted clinical decision if (A) a patient was enrolled onto a genotype-matched clinical trial or (B) prescribed off-label an FDA-approved therapy targeting an identified mutation. The frequency of mutated genes was determined.

Results: A total of 117 patients with stage IV breast cancer were identified. Median age was 46 (25-75). Fifty-three patients (45%) had ER-positive/HER2-negative disease, 50 (43%) had ER-negative/HER2-negative disease, and 14 (12%) had ER-any/HER2-positive disease. Median number of previous therapies received prior to genomic profiling was 2 (range 0-15), and median follow-up after testing was obtained after 5.8 months (range 0-24.4 months). Commercial reports indicated that 85 (73%) patients had at least one mutation targetable by an FDA-approved medication, and 112 (96%) patients had at least one clinical trial available; however, clinical management was only affected in 11 patients (9%). The most frequent mutations observed were those in TP53, FGF, PI3KCA, MYC, ZNF, FGFR, CCND, ARID1A, GATA3, and MAP; frequencies of these mutations varied by clinical subtype.

Conclusions: Tumor genomic profiling affected clinical management in a minority of patients with metastatic breast cancer, thus these data do not support the routine use of genomic profiling outside of a clinical trial.

Keywords: Breast cancer; Clinical behavior; Clinical utility; Genomic profiling.

MeSH terms

  • Academic Medical Centers
  • Adult
  • Aged
  • Alleles
  • Biomarkers, Tumor*
  • Biopsy
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / therapy
  • Clinical Decision-Making*
  • Disease Management
  • Female
  • Gene Expression Profiling* / methods
  • Gene Frequency
  • Genomics* / methods
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasm Staging

Substances

  • Biomarkers, Tumor