Ricerc@Sapienza

The pathway PD1/PD-L1 is a key player in the mechanism of tumor escape from immune surveillance but, the role of PDL1 as a marker of outcome in breast cancer patients is still unclear to date. We aim to analyze PD-L1 expression on circulating tumor cells during neoadjuvant chemotherapy (NACT) in locally advanced breast cancer patients. In our opinion, CTCs better than other samples can describe molecular portrait of the tumor, being a critical step in the metastatic process and quite often present in the blood in the very early phase of neoplastic disease. Moreover, serial liquid biopsies investigating PD-L1 expression could recreate a dynamic portrait of the cancer complexity able to inform on the genomic heterogeneity during treatment. To date, PD-L1 expression on breast CTCs during NACT has never been investigated. We hope in the future liquid biopsy could guide breast cancer management, as a tool that very early intercept ensuing resistance before clinical tumor progression, allowing prompt treatment modifications. Moreover, PD-L1 positive CTCs could be a very promising biomarker to predict pRC or to early identify patients with poor response to treatment, who need a more aggressive treatment and a closer follow up. Preliminary results show a high expression of PD-L1 positive CTCs in BRCA1/2 mutated breast cancers, regardless of intrinsic subtype, with the highest rate found in basal breast cancers. This observation support the hypothesis that PD1/PDL1 pathway could be the principal mechanism of the immune escape in BRCA1/2 mutated cancer and in all tumors with DNA repair mechanism defects.