Abstract P5-07-06: Genomic characterization and tumor evolution in matched(primary-relapse)samplesof patients with METAPLASTIC breast cancer
Authors: Cejuela Mónica , Stradella Agostina , Petit Anna , Gargallo Pablo , Bosch Jan , Carbonell Paula , Recalde Sabela , Vethencourt Andrea , Fernández Adela , Falo Catalina , Gil-Gil Miguel , Vazquez Silvia , Villanueva Rafael , Soler Teresa , Calabria Inés , Pernas Sonia 
Published: March 2022

Abstract
Introduction and objectives. Metaplastic breast cancer is an heterogenous and infrequent disease (0.5-2%). Histologically, it is defined by differentiation of neoplastic epithelium into squamous or mesenchymal-like elements. Although they are mainly triple negative tumors, they present a more aggressive course with less response to chemotherapy and worse prognosis. The aim of our study was to characterize the molecular profile and tumor evolution in matched (primary-relapse) samples of patients (pts) with metaplastic breast cancer. Material and Methods. Genomic profiling of tumor biopsies from different time points in patients with early-stage metaplastic breast cancer who had disease recurrence/progression, and were treated at our institution between 2010 and 2020. Tumor samples were analyzed by DNA- Next Generation Sequencing (NGS; Illumina 2x75bp) using the ActionOncoKitDX panel (Imegen-Health in Code group). It allowed the study of point mutations in 50 genes, CNVs, fusion genes among 8 genes and pharmacogenetic SNPs associated with treatment efficacy or toxicity. It also determined MSI through 110 markers. The results were classified following the recommendations of the ACMG (American College of Medical Genetics). Only pathogenic and likely pathogenic variants were considered for analysis and afterwards we categorized them following the ComPerMed (The Personalized Medicine Commission) criteria. Results. We have analyzed 21 matched diagnosis-relapse tumor samples (8 primary tumor samples, and 13 loco-regional or metastatic disease) from 8 patients. In 4 patients, genomic characterization was performed at 3 different time points of their tumor evolution. Pathogenic alterations identified were mutations in TP53 (in 100% of the samples), TERT promoter (29%), and MYC amplifications (24% of samples, of which 75% were relapse/progression samples). We didn’t find any mutation in PI3KCA, but PTEN was found to have variations in 38% samples (10% mutations and 38% deletions). Amplification of FGFR1 was identified in 13% of the pts (only in the primary tumor). No ERBB2 or EGFR gene amplifications were detected, neither high grade MSI. We did not find a significant increase in point mutations between primary and relapse/progression samples, although gene amplifications were found more frequently in the former ones. Sixty three percent of the cases were Tier I and II category alterations, which could have future implications in the management of this neoplasia. Conclusion. In our series of metaplastic carcinoma, the most frequent pathogenic alterations occurred in cycle regulation’s genes, including TP53 and TERT promoter mutations, and MYC amplifications. Relapse/progression samples were enriched in MYC amplification and inTP53 allelic frequency. Larger studies are required to better characterize these tumors, and identify new strategies to improve the prognosis of these patients.
Citation Format: Mónica Cejuela, Agostina Stradella, Anna Petit, Pablo Gargallo, Jan Bosch, Paula Carbonell, Sabela Recalde, Andrea Vethencourt, Adela Fernández, Catalina Falo, Miguel Gil-Gil, Silvia Vazquez, Rafael Villanueva, Teresa Soler, Inés Calabria, Sonia Pernas. Genomic characterization and tumor evolution in matched(primary-relapse)samplesof patients with METAPLASTIC breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-07-06.