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

## TL;DR

This study finds that young adults with metastatic breast cancer have unique genetic profiles compared to older patients, highlighting the potential for personalized treatment through liquid biopsies.

## Contribution

The study identifies distinct genomic alterations in young adults with metastatic breast cancer, emphasizing the importance of age-specific molecular profiling.

## Key findings

- Young adults with metastatic breast cancer show higher frequencies of TP53, ESR1, and PTEN alterations compared to older patients.
- 79% of young adults with metastatic breast cancer have actionable genomic alterations according to ESCAT tiers.
- Cell cycle and DNA damage response pathway alterations are more common in young adults with breast cancer.

## Abstract

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.

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.

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).

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.

•Young adults with metastatic breast cancer present distinct genomic profiles in comparison to older patients.•In young adults with metatatic breast cancer, 79% present actionable ESCAT I-IV and ESCAT I-III genomic alterations.•Cell cycle and DNA damage response pathway alterations were more common in young adults.•These findings underline the potential impact of liquid biopsy in young adults for a genome-guided personalized therapy.

Young adults with metastatic breast cancer present distinct genomic profiles in comparison to older patients.

In young adults with metatatic breast cancer, 79% present actionable ESCAT I-IV and ESCAT I-III genomic alterations.

Cell cycle and DNA damage response pathway alterations were more common in young adults.

These findings underline the potential impact of liquid biopsy in young adults for a genome-guided personalized therapy.