Association between PIK3CA Mutations in Blood and Tumor-Infiltrating Lymphocytes in Peruvian Breast Cancer Patients

Abstract

Objective: To evaluate the relationship between circulating tumor DNA (ctDNA) presence and tumor features including tumor-infiltrating lymphocyte (TIL) levels in Peruvian breast cancer patients. Materials and Methods: This was a prospective study conducted at the Instituto Nacional de Enfemedades Neoplasicas, Peru. We evaluated level of TIL and PIK3CA mutations in ctDNA. Clinical characteristics, including outcome data, were collected from the patient file. Survival was calculated from the date of blood sample drawn to the event time. Data collected were analyzed using SPSS software version 25. Results: We analyzed plasma samples from 183 breast cancer patients. most cases were of Luminal-B (44.8%) phenotype and stage II (41.5%), and median stromal TIL was 30%. PIK3CA mutation in ctDNA was detected in 35% cases (most with E545K) and was associated with lower TIL level (p=0.04). PIK3CA in ctDNA tended to be associated with advanced stages (p=0.09) in the whole series and with higher recurrence rates (p=0.053) in the non-metastatic setting. Patients with presence of PIK3CA in ctDNA tended to have shorter survival (p=0.083). Conclusion: Presence of PIK3CA mutation in ctDNA was frequently found in our Peruvian breast cancer series, was associated with lower TIL levels and tended to predict poor outcomes.

Circulating Tumor DNA in Human Papillomavirus–Mediated Oropharynx Cancer

“…De Sarkar et al 77 demonstrated that specific prostate cancer ctDNA profiles had nucleosome patterns associated with transcriptional activity in key regions. Studies in breast cancer have shown that PIK3CA mutations, high DNA integrity, and ALU 247 repeat elements were associated with lower levels of tumor-infiltrating lymphocytes, as well as poor outcomes 78,79 . Furthermore, variable posttreatment PIK3CA levels may be explained by intratumoral heterogeneity in advanced breast cancer 80 .…”

“…Studies in breast cancer have shown that PIK3CA mutations, high DNA integrity, and ALU 247 repeat elements were associated with lower levels of tumor-infiltrating lymphocytes, as well as poor outcomes. 78,79 Furthermore, variable posttreatment PIK3CA levels may be explained by intratumoral heterogeneity in advanced breast cancer. 80 In summary, these data suggest promise for using ctDNA assays to reveal information regarding tumor phenotypes and microenvironment; however, further studies are needed in HPV-mediated oropharyngeal cancer.…”