Clinical Relevance of Tumour-Infiltrating Immune Cells in HER2-Negative Breast Cancer Treated with Neoadjuvant Therapy.

Currently, therapy response cannot be accurately predicted in HER2-negative breast cancer (BC). Measuring stromal tumour-infiltrating lymphocytes (sTILs) and mediators of the tumour microenvironment and characterizing tumour-infiltrating immune cells (TIICs) may improve treatment response in the neoadjuvant setting. Tumour tissue and peripheral blood samples were retrospectively collected from 118 patients, and sTILs were evaluated. Circulating exosomes and myeloid-derived suppressor cells were determined by flow cytometry. TIICs markers (CD4, CD8, CD20, CD1a, and CD68) were assessed immunohistochemically. High sTILs were significantly associated with pathological complete response (pCR; p = 0.048) and event-free survival (EFS; p = 0.027). High-CD68 cells were significantly associated with pCR in triple-negative (TN, p = 0.027) and high-CD1a cells with EFS in luminal-B (p = 0.012) BC. Cluster analyses of TIICs revealed two groups of tumours (C1 and C2) that had different immune patterns and clinical outcomes. An immunoscore based on clinicopathological variables was developed to identify high risk (C1) or low-risk (C2) patients. Additionally, cluster analyses revealed two groups of tumours for both luminal-B and TNBC. Our findings support the association of sTILs with pCR and show an immunological component in a subset of patients with HER2-negative BC. Our immunoscore may be useful for future escalation or de-escalation treatments.

Secreted Protein Acidic and Rich in Cysteine (SPARC) Polymorphisms in Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer Patients.

Secreted protein acidic and rich in cysteine (SPARC) expression has been proposed as a prognostic and predictive biomarker for some cancer types, but knowledge about the predictive value of SPARC polymorphisms in the context of neoadjuvant therapy for breast cancer (BC) is lacking. In 132 HER2-negative BC patients treated with neoadjuvant chemotherapy, we determined polymorphisms in the SPARC gene and analyzed their association with outcome. We also determined SPARC protein expression in tumor tissue. SPARC rs19789707 was significantly associated with response to treatment according to the Miller and Payne system in the breast (multivariate: odds ratio (OR), 3.81; p = 0.028). This association was significant in the subgroup of patients with luminal tumors (univariate: p = 0.047). Regarding survival, two SPARC variants showed significant associations with event-free survival: the rs19789707 variant in the subgroup of luminal A tumors (univariate: p = 0.006), and the rs4958487 variant in the subgroup of luminal B tumors (univariate: p = 0.022). In addition, SPARC rs4958487, rs10065756, and rs12153644 were significantly correlated with SPARC protein expression. Our findings suggest that SPARC polymorphisms could be good predictors of treatment response and survival in BC patients treated with neoadjuvant chemotherapy, especially those with luminal tumors.