167P - A tumor immune microenvironment-based model for prediction of everolimus efficacy in premenopausal women with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Preliminary results from MIRACLE trial

Background

Everolimus (EVE), a mammalian target of rapamycin (mTOR) inhibitor, has been proven beneficial for patients with HR⁺/HER2⁻, advanced breast cancer (ABC) with endocrine resistance. Preclinical studies showed mTOR has close relationships with the tumor immune microenvironment (TME). Therefore, this study aimed to identify TME-related markers to predict efficacy of EVE in patients with HR⁺/HER2⁻ ABC.

Methods

Tumor tissues of patients from Miracle trial receiving EVE were collected for NanoString RNA expression analysis. TME cell type and TME signatures associated with efficacy were identified using the 289-immuno-gene panel of NanoString nCounter platform. Multiple statistical approaches were applied for enrichment analyses, survival estimation and validation.

Results

Mast cell scores significantly increased in patients who did not respond to EVE (P = 0.031) and those who had progression-free survival (PFS) < 6 months (P = 0.029). CD8 T cells were highly infiltrated in tumor tissue from patients with PFS < 1 year (P = 0.035). Patients with PFS > 1 year had lower scores of chemokines (P = 0.032) and Teff (P = 0.028) than those with PFS < 6 months did. Histidine decarboxylase (HDC), TNF receptor superfamily member 1A (TNFRSF1A), and RAD51 correlated with PFS and EVE response. Patients with HDC (P = 0.013) or TNFRSF1A (P = 0.0031) overexpression showed shorter PFS, whereas patients with RAD51 overexpression showed prolonged PFS (P = 0.049). A predictive model comprising HDC, TNFRSF1A, and RAD51 was established, and the receiver operating characteristic curve demonstrated its superiority (AUC = 0.96). The results also showed that patients whose tumors were non-responsive to EVE (P = 0.00021) or whose PFS was poor (P = 0.0025) were at a higher risk in the model.

Conclusions

The immune-related gene model consisting of HDC, TNFRSF1A, and RAD51 could potentially predict the efficacy of EVE in premenopausal patients with HR⁺/HER2⁻ ABC with endocrine resistance, which could help stratify responders to EVE and guide the choice of EVE in clinical practice.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.