Triple-negative Breast Cancer: a New Perspective on Biomarkers (TNBCbrazil)

Instituto Nacional de Cancer, Brazil

Status: Completed

Conditions: Triple Negative Breast Neoplasms; Triple Negative Breast Cancer

Study type: Observational

Funder types: Other

Identifiers

NCT03539965

TNBCbrazil

Details and patient eligibility

About

A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.

Full description

Background/Rationale: Triple negative breast cancer (TNBC) is known to be a heterogeneous disease, and different molecular sub-classifications are proposed based in specific biomarkers as immunohistochemical (IHC) expression of the androgen-receptor (AR), Epidermal growth Factor Receptor (EGFR), Cytokeratin 5/6 (CK5/6), Cytokeratin14 (CK14), Cytokeratin 17 (CK17), clusters of differentiation 117 (CD 117), p53, Ki67 level, Programmed cell death-ligand 1 (PD-L1) and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes (PD-1+, FOXP3+, CD 4+ or cluster designation 8 (CD8 +), CD 3+, cluster of differentiation 56 (CD56+), cluster designation 68 (CD68+) or CD 14+). Predicting response and survival to neoadjuvant treatment of locally advanced triple-negative breast cancer remains a major challenge. Many doubts still prevail over the role of new biomarkers in predicting different outcomes for tumors with the same stage and morphological characteristics.

Objectives and Hypotheses:

Primary objective: To evaluate the association of the intratumoral lymphocytic infiltrate (TILs) status profile in the core biopsy with complete pathological response (CPR) outcomes to neoadjuvant chemotherapy and progression-free survival (PFS). Secondary objectives: To evaluate the association of the others biomarkers expression profile and the quality of TILs with PFS and CPR. To determine the prevalence of a large immunohistochemical panel (AR, EGFR, CK5/6, CK14, CK17, CD 117, p53, Ki67 level, PD-L1 and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes PD-1+, FOXP3+, CD 4+ , CD8 +, CD 3+, CD56+, CD68+ and/or CD 14+), before and after neoadjuvant chemotherapy. To determine if the negativation of biomarkers after the systemic treatment is associated with CPR and PFS.

Methods:

Study design: A cohort with retrospective data collection and sectional analysis of pathological material.

Data Source(s): Medical records and pathological material. Study Population: Women with locally advanced triple negative breast cancer consecutively enrolled at Brazilian National Cancer Institute (INCA) submitted to neoadjuvant treatment and subsequently operated.

Exposure(s): Status of specified biomarkers. Outcome(s): Complete Pathologic Response and Progression free Survival and Sample Size Estimations: With a type I error of 5% and study power of 80%, it is estimated that 155 patients are needed.

Statistical Analysis: Statistical analysis will be performed using SPSS (version 18.0 for windows, statistical package for social science (SPSS) Inc., Chicago, IL). Survival curves will be constructed using the Kaplan-Meier method.

Enrollment: 239 patients

Sex: Female

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women older than 18 years
• Locally advanced TNBC (T3-4, any Node, M0; any Tumor, N1-3, M0)
• Patients submitted to anthracycline and taxane-based neoadjuvant chemotherapy and then operated between January 2010 and December 2014 at the Brazilian National Cancer Institute.

Exclusion criteria

• Patients with metastatic Breast Cancer;
• Other non-epithelial histologies of breast cancer;
• Pure Ductal Carcinoma In Situ diagnoses are not eligible.
• Patients with scarce material for immunohistochemistry;
• Other primary synchronous or anachronistic tumors in the breast or other sites;
• No prior immunotherapeutic, chemotherapeutic or antiandrogenic drugs allowed
• Patients treated with alternative neoadjuvant chemotherapy regimens (not based on anthracycline and taxane) or with only hormone therapy;
• Patients who received chemotherapy or who were operated outside the INCA.

Trial design

239 participants in 1 patient group

Single-arm cohort

Description:

Initially, patients will be analyzed in a single group. After determining the status of the biomarkers, the patient sample will be divided into specific groups for comparative purposes.