Avaliação multimodal de respondedores excepcionais refinar tratamento de precisão dirigido por subtipagem no câncer de mama HR+/HER2

Resumo original em inglês

O que aconteceu

We previously defined 4 hormone receptor + /human epidermal growth factor receptor 2 – (HR + /HER2 – ) subtypes: SNF1 canonical luminal, SNF2 immunogenic, SNF3 proliferative, and SNF4 RTK driven. The FASCINATE-N proof-of-concept trial demonstrated that subtyping-directed precision treatment improves pathologic complete response in locally advanced HR + /HER2 – breast cancer, yet efficacy remains suboptimal

We integrated transcriptomic, genomic, digital pathology, and clinical data from this trial ( n = 230) and focused on exceptional responders to explore opportunities for refining treatment strategies

National Natural Science Foundation of China, grant numbers U25C2032, 82441028, and 82573645; The Shanghai Key Laboratory of Breast Cancer, grant number 12DZ2260100; The Human Phenome Data Center of Fudan University

ClinicalTrials.gov identifier: NCT05582499

O que encontraram

In SNF1, we uncovered that perineural invasion diminished endocrine therapy efficacy, suggesting the potential benefit of incorporating perineural blockade. Digital pathology and spatial transcriptomics identified that the spatial architecture of the tumor-stromal-immune interface influenced apatinib efficacy in SNF4, highlighting the importance of interfering with the tumor microenvironment. In the SNF3 group, exceptionally well responders exhibited multiple mutations in DNA repair genes and cell cycle activation, correlating with the efficacy of poly (ADP-ribose) polymerase and CDK4/6 inhibitors. Additionally, we illustrated that lymphatic vessel infiltration was linked to improved immunotherapy outcomes in HR + /HER2 – SNF2 tumors

Por que isso importa

Overall, our study emphasizes the importance of multimodal assessments in optimizing precision treatments for HR + /HER2 – breast cancer

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.