Triple-negative Breast Cancer: a New Perspective on Biomarkers

Triple Negative Breast Cancer Clinical Trial

— TNBCbrazil  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03539965
• Other study ID #: TNBCbrazil
• Status: Completed
• Start date: January 1, 2010
• Est. completion date: December 31, 2014

Study information

• Verified date: May 2018
• Source: Instituto Nacional de Cancer, Brazil
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 239
• Est. completion date: December 31, 2014
• Est. primary completion date: December 31, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Locations

Country	Name	City	State
Brazil	Instituto Nacional do Cancer - CPQ	Rio De Janeiro

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancer, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	The first event defined as local recurrence or distant relapse, or death, whichever come first.	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.
Secondary	Clinical Response Rate	To determine the clinical response rate in patients with palpable disease.	From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Secondary	Objective response rate	To compare overall objective response rate in both treatment groups.	From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Secondary	Determine predictive markers	To determine predictive markers for sensitivity and resistance to chemotherapy.	Approximately 24 weeks: from diagnosis up to surgery.
Secondary	Determine prognostic markers	To determine prognostic markers for progression free survival after neoadjuvant chemotherapy and surgery.	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.