Abstract 261P
Background
About 50% of BC presented with HER2-low expression. There is a paucity of markers apt to characterize this novel subtype, defined by HER2 immunohistochemistry score of 1+ or 2+ with negative in situ hybridization assay. The aim of this study was to explore the role of liquid biopsy–based biomarkers for the characterization of HER2-low metastatic breast cancer (mBC).
Methods
A cohort of 81 patients (pts) with HR+ HER2-negative mBC was prospectively enrolled in the CRO-2018-56 study and characterized for ctDNA through droplet digital PCR (ddPCR) and next generation sequencing (NGS) before treatment start (BL). ESR1 epigenetic status was defined by assessing the methylation of its main promoters (promA and promB). Associations were tested through Mann–WhitneyU test and Fisher exact test, matched pairs variations through Wilcoxon signed rank test; survival was analyzed by log-rank test.
Results
In the total population HER2 0 mBC patients (pts) were 40 (49%) and HER2-low were 41 (51%). No significant association with the number of metastatic sites and metastatic lesions was detected for HER2-low (P=0.87 and P=0.78 respectively). Pts with low expression of HER2 showed a comparable outcome in terms of PFS at first-line (at 12 months 81% vs 70% P=0.38) and OS (at 12 months 91% vs 97% P=0.37). At BL, ctDNA-detected ESR1 and PIK3CA mutations (muts) were respectively found in 11% and 21% of pts in the HER2 0 cohort and in 8% and 31% of pts in the HER2-low cohort. No differences in distribution were observed (P=1 for ESR1;P=0.8 for PIK3CA). ACTB short fragments weren’t significantly different in pts with HER2-low disease (P=0.95).Moreover, in HER2-low mBC the median methylation for promA was 56% vs 52.3% and for promB resulted 42.9% vs 55% with no significant differences (P=0.78 and P=0.40).
Conclusions
This study characterized a prospective cohort of HER2-low and HER2 score 0 MBC, showing no significant differences for endocrine resistance biomarkers on a mutational and epigenetic standpoint. Since novel antibody drug conjugates are gaining momentum as a viable treatment strategy in luminal-like mBC, highlighting biomarkes linked to intrinsic endocrine resistance will be of pivotal importance for tailoring therapeutic sequences.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University of Udine.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.