Detection of ESR1 circulating mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of ESR1 circulating mutations at the end of the 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 ESR1 circulating mutation frequency at the end of adjuvant treatment in patients with a subsequent local or metastatic 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 at least 6 months after the end of their treatment. ESR1 circulating mutations (D538G, Y537S/N/C) were detected by droplet digital PCR in plasma samples taken both at the end of adjuvant treatment and on AI progression in patients re-exposed to AI during the metastatic phase.
A total of 39 patients were included, with a median adjuvant AI exposure of 60 months (range 41-85). One patient (2.6%) had a local relapse only, while all the others (97.4%) had a metastatic relapse during follow-up. Median delay between the end of adjuvant treatment and relapse was 25 months (range 6-71). No ESR1 circulating mutation was detectable at the end of AI adjuvant therapy. In contrast, among the 25 patients (64%) who progressed on AI during the metastatic setting, 17 plasma samples were available and 7 patients (41,2%) had a detectable mutation.
Our results highlighted that there is no emergence of circulating ESR1 mutation at the end of an AI-based adjuvant treatment in hormone receptor positive breast cancer patients. In contrast, and as expected, we showed that re-exposure to AI in the metastatic setting induced circulating mutation detection in a significant fraction of the patients. Our present findings point out the low interest in ESR1 circulating mutation detection during the adjuvant setting, even for patients that will relapse.
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Centre Henri Becquerel
All authors have declared no conflicts of interest.