66P - Molecular profile of triple-negative breast cancer tumours and their association with response to neoadjuvant treatment: A study using next generation sequencing

Background

Triple-negative breast cancer (TNBC) presents therapeutic challenges due to its molecular heterogeneity and lack of specific targeted therapies. European Society for Medical Oncology guidelines emphasize multigene next-generation sequencing (NGS). There's limited information on its application in TNBC. Pathologic response is a surrogate marker for overall survival (OS).

Methods

Retrospective study analyzed 43 TNBC patients receiving Neoadjuvant Chemotherapy (NAC) at Hospital de Denia. NGS was performed on pre and post-NAC biopsies and paired with clinicopathological data. Statistical analysis was performed using the R statistical programme.

Results

Data revealed associations between KDR mutations and patients with a smoking history (p=0.046), as well as a diminished response rate to NAC across all patients (33% vs 73%, p=0.0127). NOTCH1 and CDKN2A mutations correlated with higher mutational burden (p<0.0001). TP53 immunohistochemistry significantly correlated with OS and disease-free survival (DFS) among patients achieving complete pathological response (pCR) (p=0.0023, p=0.0002). KIT mutations also impacted DFS in responders to NAC (p=0.03). Additionally, long-term breastfeeding correlated positively with NAC response (p=0.023), lesser tumour mutational burden, including notch1 (p=0.0177), cdkn2a (p=0.025), and c-kit mutations (p=0.028).

Conclusions

Our findings show the critical significance of genomic profiling, particularly KDR, NOTCH1, CDKN2A, and TP53 genes, in predicting TNBC response to NAC. The observed correlation between breastfeeding duration and outcomes introduces a novel dimension to TNBC. This supports the potential impact of lifestyle factors on therapeutic response and the sociological implications of breastfeeding practices, not only in mitigating TNBC risk but also in shaping favorable treatment responses. Further exploration of this relationship is essential to inform integrative approaches to TNBC care to optimize outcomes.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

J.M. Gasent Blesa.

Funding

Universidad CEU Cardenal Herrera.

Disclosure

All authors have declared no conflicts of interest.