Genomic landscape of metastatic breast cancers in young adults: a liquid biopsy analysis of women aged 20-40 years.

INTRODUCTION: Breast cancer in young adults (YA) aged 20-40 years has distinct clinical and biological traits compared with older patients. This study evaluated the genomic landscape of metastatic breast cancers (MBC) among YA. METHODS: Patients with MBC enrolled in the STING molecular profile platform (NCT04932525) between 2021 and May 2023 were included. Clinical and genomic features were analyzed by age (≤40 vs > 40 years). Tumor profiling used the FoundationOne Liquid CDx assay (324 genes) at baseline or later in the disease course. Variant frequencies were compared across age groups. RESULTS: Of 432 eligible patients, 68 (16 %) were YA. Among 37 YA with hormone receptor positive (HR+) BC, frequent alterations included TP53 (39 %), ESR1 (27 %), PIK3CA (25 %), FGFR3 (18 %), FGFR4 (18 %), FGFR19 (18 %), CCND1 (18 %). Compared with older patients, YA with HR + tumors had fewer RB1 (7 % vs 8 %; p = 0.03) and PIK3CA (25 % vs 31 %; p = 0.03) alterations. Among 28 YA with triple negative BC, the most common alterations were TP53 (100 %), PTEN (26 %), BRCA1 (22 %), RB1 (17 %). PTEN mutations were more frequent among YA with TNBC than older patients (26 % vs 8 %; p = 0.009). Tiers I-III genomic alterations according to the ESMO scale of clinical actionability (ESCAT) were identified in 54 YA (79 %), including 48 tiers I-II alterations comprising ESR1 (n = 12), gBRCA1/2 (n = 11), PIK3CA (n = 13). CONCLUSIONS: ESCAT tiers I-III alterations were reported in 79 % YA with MBC which supports the role of molecular profiling in YA. The differences detected in the genomic profiles of YA with BC and older patients may allude to potential different underlying disease biology.