The Genomic Landscape of Breast Cancer in Young and Older Women

• Published in: Clinical breast cancer Vol. 24; no. 7; pp. 630 - 638.e3
• Main Authors: Heeke, Arielle L., Sha, Wei, Feldman, Rebecca, Fisher, Julie, Hadzikadic-Gusic, Lejla, Symanowski, James T., White, Richard L., Tan, Antoinette R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2024
• Subjects: Molecular profiling; Mutation; Older women breast cancer; Prognosis; Young women breast cancer; Molecular profiling; Prognosis; Mutation; Young women breast cancer; Older women breast cancer
• ISSN: 1526-8209; 1938-0666; 1938-0666
• DOI: 10.1016/j.clbc.2024.07.008

•Distinct molecular aberrations exist between breast cancers from young and older patients.•Tumors from younger patients are more often characterized by alterations in inherent oncogenic drivers (eg, BRCA1/2, TP53).•Tumors from older patients may display more cumulative genetic events, with higher rates of PIK3CA mutations, increased immunotherapy biomarkers, and increased expression of the androgen receptor.•Considering these genomic differences could refine treatment strategies for young and older breast cancer patients. Young women with breast cancer (YWBC; ≤40 years) often have a poorer prognosis than older women with breast cancer (OWBC; ≥65 years). We explored molecular features of tumors from YWBC and OWBC to identify a biologic connection for these patterns. We retrospectively analyzed the molecular profiles of 1879 breast tumors. Testing included immunohistochemistry (IHC), in situ hybridization (ISH), and next-generation sequencing. Statistical analyses included Pearson's chi2 test for comparisons, with significance defined as FDR (false discovery rate)-P < .05. TP53 and BRCA1 somatic mutations were more common in YWBC tumors than in OWBC tumors (53%, 42%; P = .0001, FDR-P = .0025 and 7%, 2%; P = .0001, FDR-P = .0025; respectively). Conversely, OWBC tumors had higher androgen receptor expression (55%, 45%; P = .0002, FDR-P = .0025) higher PD-L1 expression detected by IHC (8%, 5%; P = .0476, FDR-P = .2754), and more frequent PIK3CA mutations (33%, 17%; P = < .0001, FDR-P = < .0001). Among HR+/HER2- samples, YWBC had more gene amplifications in FGF3 (27%, 10%; P = .0353, FDR-P = .2462), FGF4 (27%, 9%; P = .0218, FDR-P = .1668), FGF19 (30%, 12%; P = .034, FDR-P = .2462) and CCND1 (37%, 18%; P = .0344, FDR-P = .2462) than OWBC. Our data suggest distinct molecular aberrations exist between YWBC and OWBC. Exploiting these molecular changes could refine our treatment strategies in YWBC and OWBC. Young women with breast cancer have a poorer prognosis which may relate to specific molecular features of their breast tumors. Herein we retrospectively analyzed molecular profiles of 1879 breast tumors from younger and older patients. Our data found distinct molecular aberrations exist between younger and older patients with breast cancer.