Incorporating Genomics Into the Care of Patients With Advanced Breast Cancer

Abstract

Metastatic breast cancer is a very heterogeneous disease. Recent advances in genomic sequencing have revealed genetic diversity between patients and across distinct subclonal cell populations within the same patient that may evolve across metastatic tumor sites and during treatment. With the increasing availability of commercial and laboratory-developed tests that can detect genomic alterations from patient tumor and blood samples, translating this knowledge into improved clinical care remains a challenge. The goals of this review are to outline the clinical relevance of tumor genomic heterogeneity and clonal evolution, to help clinicians understand how to interpret genomic testing reports, and to provide an overview of recurrent genomic alterations that may be relevant for clinical trials with investigational drug treatments.PRACTICAL APPLICATIONSGenomic sequencing can provide important information about tumor heterogeneity and clonal dynamics. Measures of clonal heterogeneity are relevant for prognostication or prediction of benefit from treatment, understanding the metastatic process, and identifying mechanisms of treatment resistance Targeted panel genomic tests on tumor are robust to small tumor fraction and are currently most relevant to routine clinical practice. Variant allele fraction can hint at heterozygosity and whether the mutation is present in germline. Patients with advanced breast cancer who have recurrent genomic alterations detected by targeted panel tests—such as ERBB2, PIK3CA, AKT1, and ESR1 mutations; NTRK fusions; dMMR; or high tumor mutational burden—should be considered for early referral for clinical trials