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

Sponsor

Instituto Nacional de Cancer, Brazil (Other)

Overall Status

Completed

CT.gov ID

NCT03539965

Collaborator

(none)

239

Enrollment

Location

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Neoplasms Triple Negative Breast Cancer

Detailed 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.

Study Design

Study Type:

Observational

Actual Enrollment :

239 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Triple-negative Breast Cancer: a New Perspective on Predictive and Prognostic Biomarkers

Actual Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Dec 31, 2014

Actual Study Completion Date :

Dec 31, 2014

Arms and Interventions

Arm	Intervention/Treatment
Single-arm cohort 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.

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.]
The first event defined as local recurrence or distant relapse, or death, whichever come first.

Secondary Outcome Measures

Clinical Response Rate [From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks]
To determine the clinical response rate in patients with palpable disease.
Objective response rate [From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks]
To compare overall objective response rate in both treatment groups.
Determine predictive markers [Approximately 24 weeks: from diagnosis up to surgery.]
To determine predictive markers for sensitivity and resistance to chemotherapy.
Determine prognostic markers [Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.]
To determine prognostic markers for progression free survival after neoadjuvant chemotherapy and surgery.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts 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.