Tumour stroma characterization for the clinical stratification of HR+/HER2- breast cancer

Background & objectives: Tumour microenvironment (TME) plays a pivotal role in the prognosis and therapeutic response in several types of cancer. Our study aimed to characterize TME cellular composition of HR+/HER2- breast cancer (BC) to gain insight into tumour development and disease progression. Methods: Tissue Microarrays from 70 HR+/HER2- BC patients have been created. Imaging analysis (HALO®) was used to assess immunohistochemical expression of senescence markers (p16, α-SMA) and collagen (Masson stain). Statistical analysis was performed using GraphPad Prism Software. The study was approved by the local Ethical Committee. The project was partially funded by the 2023 Fellowship Program promoted by Gilead Sciences. Results: Nuclear p16 expression in stromal cells was significantly higher in the non-metastatic than in the metastatic group (P=0.02). Survival analysis showed that % of α-SMA expression in stromal cells higher than 30 (median value) is indicative of a poor prognosis. In detail, patients with α-SMA expression exceeding 30% exhibit significantly shorter overall survival (Chi-square=6.635 and P=0.0100) compared to those with lower expression levels. Moreover, correlation analysis showed that deposition of collagen (quantified as the area of collagen/total area of tissue core) was associated with the proliferative index of cancer cells (P=0.008). Conclusion: This study confirms the complexity of TME in BC and proposes novel markers for assessing metastatic risk. Specifically, p16 may not function as inductor of TME senescence, but instead could be degraded through an IL-6-mediated mechanism, as recently proposed. In addition, our data confirm the negative impact of α-SMA on patient survival. As for collagen, further comprehensive investigations are needed to elucidate its potential impact on patient outcomes. Funding: The project was partially funded by the 2023 Fellowship Program promoted by Gilead Sciences.