1769P Circulating T cells and response to neoadjuvant chemotherapy in locally advanced breast cancer

Abstract

Background Breast cancer (BC) is the most frequent and leading cause of cancer death among women. Immune system plays a importante role in the development and prognosis of BC. T lymphocytes contribute to tumor immunosurvaillance and preclinical and clinical data indicate that the immune system influences the prognosis and response to chemotherapy. However, there are few data considering circulating T cell and its clinical relevance is not fully established in breast cancer. This study aimed to characterize the profile of circulating T, B, NK and NKT cells in patients with locally advanced breast cancer.

Methods Two prospective cohorts of women with locally advanced BC (n=80) and healthy controls (HC) (n=25). Tumor subtype distribution was as follow: 8 luminal A (LA), 26 luminal B (LB), 18 HER2 + and 28 Triple-Negative (TN). The percentage of lymphocytes (T, NK, NKT, iNKT) and their populations were determined by flow cytometry in the peripheral blood of patients prior the initiation of neoadjuvant chemotherapy (NCT). Pathological complete response (pCR) was defined as the absence of invasive neoplasia in the surgical specimen (breast and axilla). The Mann Whitney test was used for analysis between groups through the GraphPad Prism program, v6.0.

Results Patients with pCR had lower CD4+ T lymphocytes (p <0.0001) and higher TCD8+ lymphocytes (p = 0.0088) counts versus non-pCR (NpCR). LA and TN subtypes had fewer circulating CD161 + NKT cells than HC (p = 0.0039); whereas LA subtype had higher counts of CD94 + NKT cells compared to LB, HER2 +, TN and HC (p < 0.05). Total circulating iNKT cells counts was higher in patients when CS (p <0.05), and CD4 + iNKT populations were elevated in all subtypes than iNKT CD8 + (p <0.05). iNKT CD4+ count was higher in HER2+ (P = 0.03) and TN (p = 0.02), and iNKT CD8+ count was higher in LB compared to LA (p = 0.04), HER2 + (p = 0.04) and HC (P = 0.02). The count of iNKT CD4+CD8 + was lower than HC in LA (p = 0.02), LB (p = 0.002) and TN (p = 0.003). The percentage of circulating CD4 + CD8 + iNKT cells were reduced in lymph node positive (LN+) BC (p = 0.02) compared to those with LN- and in NpCR (p = 0.02).

Conclusions The cellular immune response profile in peripheral blood varies according to the subtype of breast cancer, and may be predictive of pCR and of lymph node involvement.