Molecular Concordance Between Primary Breast Cancer and Matched Metastases

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▪ Abstract:

Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both with respect to traditional clinical treatment targets and on the genomic and transcriptomic level. With the increasing use of molecularly targeted therapy, discordance of actionable molecular targets between primary tumors and recurrences can result in nonoptimal treatment or unnecessary side effects. The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight into the biology underlying metastatic progression and has the potential to identify novel, potentially druggable, drivers of progression. ▪

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