Abstract 3746: Genomic landscape in metaplastic breast cancer: Results from the AACR GENIE Database

Abstract Background: Metaplastic breast cancer (MPBC) is a rare, heterogeneous invasive subtype of breast cancer with predominant triple negative receptor status. MPBC typically has limited treatment options and portends to a poorer prognosis. Here, we focus on understanding the genomic landscape that may aid in discovering effective targeted therapies for MPBC. Methods: Using the data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR GENIE) Cohort v16.1 database, we cataloged genetic alterations in metaplastic breast cancer. ​​ Results: We identified 258 cases from 267 samples of metaplastic breast cancer. The median age known at the time of sequencing was 59 (range 25-87). Gender analysis suggested a predominantly female distribution (96.5%, n=249) compared to male (1.6%, n=4). Race/ethnicity included 62% (n=160) White, Others 25% (n=64), 6.6% (n=17) Asian, 5.8% (n=15) African American, 5.0% (n=13) Hispanic, and Native American 0.8% (n=2). Most frequent genomic alterations in the overall cohort were found in TP53 (57%, 152) with 30.3%; 81 missense and 11.2%; 30 nonsense mutations and 9%; 24 frameshift deletions; PIK3CA (34%, 90) with 30%; 80 missense mutations and 3%; 8 in frame deletions; KMT2C (17.1%, 37); KMT2D (10.8%, 31); FAT1 (13%; 29); TERT (12%; 28); KMT2D (10.5%; 25); PTEN (9.4%; 25); SPEN (10%; 22); PIK3R1 (8.3%; 20); RB1 (6.7%; 18); NF1 (7.1%; 17) genes. The most TP53 frequent mutations were seen in R248Q (14.5%; 9), R175H (8.1%; 5), Q192* (4.8%; 3), H193R (4.8%; 3), and R273C (4.8%; 3). The most frequent PIK3CA mutations were seen in H1047R (55.1%; 49), followed by E545K (14.6%; 13), Q546R (4.5%; 4), E542K (2.2%; 2), and C420R (1.1%; 1). The average mutation count was 5.0. TP53 and PIK3CA aberrations were mutually exclusive (p=0.043). Most frequent copy number alterations (deletions 66%; 181 and amplifications 34%; 93) were seen in AGO2 (22.9%, 16) RAD21 (20.4%, 19); RECQL4 (19.8%, 20); MYC (19.4%, 21); EXT1 (19%; 3); CDKN2A (14%; 15) and CDKN2B (13%; 14) genes. Conclusion: Our analysis provides valuable insights into the genetic landscape of this aggressive and rare cancer subtype. Overall, these findings support further investigation into targeted therapies for MPBC that address its unique genetic landscape, potentially improving outcomes for patients facing limited treatment options and poor prognosis. Citation Format: Blessie Elizabeth Nelson, Jacqueline Nkrumah, Mohammed Gouda, Jordi Rodon, Sarina Piha-Paul, Bora Lim. Genomic landscape in metaplastic breast cancer: Results from the AACR GENIE Database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3746.