Abstract 178P
Background
Breast cancer has afflicted more than 576000 women in 2020, one quarter of whom were younger than 50 years. A worse outcome has been associated with breast cancer at a younger age. In the luminal HER2 negative breast cancer subtype, an interaction between age and chemotherapy has been observed in younger women, consistently across the prospective trials MINDACT, TAILORx, and RxPONDER. The hypothesis that this benefit is due to an indirect effect of chemotherapy on ovarian suppression is debated. This study aims to analyze the mutational landscapes associated with age in younger versus older patients with luminal breast cancer to determine whether these genotypes could account for different diseases.
Methods
A cohort of 262 early breast cancer patients was selected from the TCGA breast cancer dataset with the following criteria: female, stage 2, ER or PR positive and HER2 negative in immunohistochemistry, negative or positive nodal status, luminal A or luminal B by PAM50. Mutational traits retrieved from TCGA were compared between younger (50 years or less) and older (more than 50 years) patients, and according to nodal status and luminal subtype.
Results
The frequency of somatic mutations among the reported 575 genes was low in young patients as in the cohort. Mutations were more diverse in older patients. Several mutated genes were found exclusively in younger patients, including CDKN1B, ERBB3, SMAD3, AKT1, EGFR, FAT1 in luminal A tumors and FOXA1, MUC1, PIK3R1 in luminal B tumors. Among them, some genes were associated with outcome. Enrichment analyses showed that these genes were involved in regulation of bone and tissue remodeling, regulation of gene silencing, or cycline-dependent protein kinases in luminal A, while involvement in EMT, stem cells, steroid signaling and T cell differentiation was observed in luminal B. The differential mutational landscape may offer opportunities to reveal druggable targets.
Conclusions
Age-related genomic heterogeneity in luminal breast cancers may impact outcomes and may be helpful for additional tailoring of therapeutics.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.