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• W4286294210 abstract "1061 Background: Molecular characterization of LMBC for the choice of therapy and inclusion in clinical trials is frequently performed in archival biopsies procured several years before. Emerging mut secondary to therapeutic pressure are hence frequently missed but could be detected by real-time analysis of circulating tumor DNA. Aim: 1) To assess the emergence of ERBB2 and other mut upon therapeutic pressure; 2) To compare the concordance of mut in tumor and plasma samples between patients (pts) with metachronous and synchronous sample acquisition. Methods: Pts with LMBC and available tumor biopsy and plasma samples were identified and divided in two groups: 1) Cohort 1 (metachronous) if the time between tissue and plasma acquisition was > 3 months and systemic treatment was given between the sampling; 2) Cohort 2 (synchronous) if sampling occurred with < 3 months interval in the absence of systemic treatment. Tumor and plasma were analyzed using MiSeq Amplicon-based NGS (custom panel of 60 cancer-related genes). The emergent mut in plasma in Cohort 1 and the concordance of ESCAT Tier I and II mut ( PIK3CA, AKT1, ERBB2, ESR1, PTEN) in both Cohorts were determined and correlated with clinical features. Results: 176 pts were included, 112 in Cohort 1 and 64 in Cohort 2. In Cohort 1, emerging mut in PIK3CA were identified in 5 cases (14% of total cases with PIK3CA mut), ESR1 in 22 cases (85% of cases with ESR1 mut) and PTEN in 3 cases (43% of cases with PTEN mut). No emerging ERBB2 or AKT1 mut were seen in plasma. In Cohort 1 ERBB2 mut were identified in 10 pts (8.9%), 5 both in plasma and tissue and 5 only in tissue. Concordance between tumor and plasma was 53% in Cohort 1 and 66% in Cohort 2 (95% CI of the difference -2% to 38%, P =.09). In Cohort 1, concordance was not associated with (neo)adjuvant treatment, number of lines for MBC, presence of visceral metastasis, location of biopsy (primary tumor or metastasis), interval between sampling (range 3.6 – 288 months) or type of systemic treatment before plasma sampling. In Cohort 2, higher concordance associated with shorter interval between primary diagnosis and sampling (p = 0.02). PI3KCA and ESR1 were the two genes most frequently altered in both cohorts. PI3KCA mut had the highest degree of concordance in both groups (70% in Cohort 1 and 76% in Cohort 2). Concordance for ESR1 mut was low in both cohorts (20% and 48%, respectively). Conclusions: A significant number of ESR1 mut emerged upon therapeutic pressure in LMBC. Plasma analysis could also detect the emergence of PIK3CA and PTEN, but not ERBB2 mut. The trend towards lower concordance between metachronous and synchronous tumor and plasma sampling is probably due to increased tumor heterogeneity and clonal diversity secondary to systemic treatment. Our findings confirm that liquid biopsies provide complementary information respect to tumor tissue that may be potentially useful for clinical decisions." @default.
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• W4286294210 date "2022-06-01" @default.
• W4286294210 modified "2023-10-16" @default.
• W4286294210 title "Utility of liquid biopsy for identifying emerging mutations (mut) and novel treatment options in luminal metastatic breast cancer (LMBC)." @default.
• W4286294210 doi "https://doi.org/10.1200/jco.2022.40.16_suppl.1061" @default.
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