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

Sep 22, 2026

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Breast cancer in young adults (20–40 years) shows distinct clinical and biological traits versus older patients. This study analyzed the genomic landscape of metastatic breast cancer among young adults using the STING molecular profile platform (NCT04932525) and FoundationOne Liquid CDx (324 genes). Among 432 patients, 68 (16%) were young adults. Results highlighted different alteration patterns by hormone receptor and age group, and 79% carried ESCAT tiers I–III actionable changes, supporting molecular profiling.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Abstract

Introduction

Methods

Results

Conclusions

Background and Rationale

Incidence and mortality in young adults

Definition of early-onset/young adulthood thresholds

Breast cancer burden and research motivation

The Breast 85 (2026) 104690 Contents lists available at ScienceDirect The Breast journal [homepage:](homepage: www.journals.elsevier.com/the-breast)[ www.journals.elsevier.com/the-breast](homepage: www.journals.elsevier.com/the-breast) | Genomic landscape of metastatic breast cancers in young adults: a liquid biopsy analysis of women aged 20–40 years | | | --- | --- | | Ernest Diab a,* , Cyril Roussel-Simonina, Federica Giuglianoa,b,c, Julia Dixon-Douglas a,d, Alessandra Spataa, Martina Pagliucaa, Lauriane Minota, Alexandre Xu-Vuillarda, Fernanda Moselec,e, Thomas Grindaa, Alessandro Viansonea, Chayma Bousriha,
Jean Zeghondya, Tarek Ben Ahmed a, Claudio Nicotrae, Arnaud Baylef,g, Antoine Italianoh, Suzette Delalogea, Barbara Pistillia,i, Fabrice Andre´ a,c, Joana Ribeiro a, Elie Rassy a,f
a Department of Cancer Medicine, Gustave Roussy, Villejuif, France b Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy c Universit´e Paris-Saclay, Gustave Roussy, Inserm U981, 94805, Villejuif, France
d Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, 305 Grattan Street, Parkville, Australia e Gustave Roussy, DITEP, Gustave Roussy, Villejuif, France
f Bureau Biostatistique et Epid´emiologie, Gustave Roussy, Universit´e Paris-Saclay, Villejuif, France
g Oncostat U1018, Inserm, Universit´e Paris-Saclay, Equipe labellis´ee Ligue Contre le Cancer, Villejuif, France
h Department of Medical Oncology, Institut Bergoni´e, University of Bordeaux, INSERM, Unit´e ACTION U1218, Bordeaux, France i Universit´e Paris-Saclay, Gustave Roussy, INSERM, Gustave Roussy, U1279, Villejuif, France | | | A B S T R A C T | | | 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. | | 1. Introduction Cancer in young adults (YA), usually referred to as ‘’early-onset cancer’’, is an emerging public health burden [1]. The incidence of cancers in YA has increased by nearly 80 % from 1990 to 2019, with early-onset cancer-related deaths also increasing by approximately 30 % [2]. While mortality rates and incidence of all cancers combined are significantly lower in younger adults than in older individuals, cancers affecting YA have important economic and social consequences and can lead to a higher number of person-years of life lost compared to those diagnosed later in lif

FAQs

What age range defines young adults in this study?

Young adults were defined as women aged 20–40 years. Analyses compared age groups using 40 as a cutoff (≤40 vs >40).

Which platform and assay were used for tumor profiling?

Patients were enrolled in the STING molecular profile platform (NCT04932525). Tumor profiling used the FoundationOne Liquid CDx assay covering 324 genes.

What were the key genomic findings in hormone receptor positive and triple negative tumors?

In hormone receptor positive cases, frequent alterations included TP53, ESR1, and PIK3CA. In triple negative cases, TP53 was most common, and PTEN mutations were reported as more frequent in young adults than in older patients.

Sep 22, 2026

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