Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients

• Published in: Breast cancer research : BCR Vol. 20; no. 1; pp. 40 - 5
• Main Authors: Allouchery, Violette, Beaussire, Ludivine, Perdrix, Anne, Sefrioui, David, Augusto, Laetitia, Guillemet, Cécile, Sarafan-Vasseur, Nasrin, Di Fiore, Frédéric, Clatot, Florian
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.05.2018; BioMed Central; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Aromatase inhibitor resistance; Aromatase Inhibitors - administration & dosage; Aromatase Inhibitors - adverse effects; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer; Cancer patients; Chemotherapy, Adjuvant - adverse effects; Circulating tumor DNA; Development and progression; Digital PCR; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Drug therapy; Early breast cancer; ESR1 mutation; Estrogen Receptor alpha - blood; Estrogen Receptor alpha - genetics; Female; Health aspects; Humans; Life Sciences; Middle Aged; Mutation; Mutation (Biology); Recurrence; Short Report; Digital PCR; ESR1 mutation; Aromatase inhibitor resistance; Early breast cancer; Circulating tumor DNA
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/s13058-018-0968-0

Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment. Circulating ESR1 mutations (D538G, Y537S/N/C) were assessed by droplet digital PCR in plasma samples taken at the end of adjuvant treatment, at time of relapse and at time of progression under first line metastatic treatment. A total of 42 patients were included, with a median adjuvant AI exposure of 60 months (range 41-85). No circulating ESR1 mutation was detectable at the end of AI adjuvant therapy. At first relapse, 5.3% of the patients (2/38) had a detectable circulating ESR1 mutation. At time of progression on first-line metastatic treatment, 33% of the patients (7/21) under AI had a detectable circulating ESR1 mutation compared to none of the patients under chemotherapy (0/10). The two patients with a detectable ESR1 mutation at relapse were treated by AI and had an increase of their variant allele fraction at time of progression on first-line metastatic treatment. Circulating ESR1 mutation detection at the end of AI-based adjuvant treatment is not clinically useful. Circulating ESR1 mutation could be assessed as soon as first relapse to guide interventional studies.