Abstract
Endocrine therapy represents the cornerstone of treatment in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). The natural course of this disease is marked by endocrine resistance, mainly due to Estrogen Receptor 1 (ESR1) acquired mutations. The aim of this study is to evaluate the concordance between ESR1 status in metastatic tumor specimens and matched circulating tumor DNA (ctDNA). Forty-three patients with HR+, HER2-negative mBC underwent both a metastatic tumor biopsy and a liquid biopsy at the time of disease progression. DNA extracted from formalin fixed paraffin embedded (FFPE) tumor specimens and ctDNA from matched plasma were analyzed by droplet digital (dd)PCR for the main ESR1 mutations (Y537S, Y537C, Y537N, D538G, E380Q). We observed a total mutation rate of 21%. We found six mutations on tissue biopsy: Y537S (1), D538G (2), Y537N (1), E380Q (2). Three patients with no mutations in tumor tissue had mutations detected in ctDNA. The total concordance rate between ESR1 status on tumor tissue and plasma was 91%. Our results confirm the potential role of liquid biopsy as a non-invasive alternative to tissue biopsy for ESR1 mutation assessment in mBC patients.
Highlights
Hormone receptor-positive (HR+) breast cancer (BC) accounts for about one third of all BC [1]
Patients were registered in a prospective database reporting demographics, clinical-pathological features, type of treatment for early and advanced BC, results for Estrogen Receptor 1 (ESR1) mutation, and follow-up data
We evaluated the concordance between ESR1 mutation analysis on matched tissue DNA and circulating tumor DNA (ctDNA) samples
Summary
Hormone receptor-positive (HR+) breast cancer (BC) accounts for about one third of all BC [1]. Several mechanisms have been linked to endocrine resistance, including mutation in Estrogen Receptor 1 (ESR1) gene. This gene, located on chromosome 6, encodes for ERa, a member of the nuclear hormone receptors superfamily [5]. ER harbors numerous bi-directional cross-talks with membrane tyrosine kinase receptors such as epidermal growth factor (EGFR), HER2, insulin-like growth factor (IGFR), that play an important role in breast cancer cells’ growth and survival [6,7,8,9]
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