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

May 29, 2018 updated by: Jesse Lopes da Silva, Instituto Nacional de Cancer, Brazil

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

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

239

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Rio De Janeiro, Brazil, 20231050
        • Instituto Nacional do Cancer - CPQ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Women who is biopsied and diagnosed with breast cancer in the public health system is referred to Brazilian National Cancer Institute (INCA) through a registry and screening performed by the Municipal Health Department of the city of Rio de Janeiro. Therefore, it becomes a great field for research of cancer patients by the large number of cases. Absolutely all patients enrolled in INCA for treatment have their biopsy material reviewed in DIPAT.

In this cohort, will be studied women with locally advanced TNBC consecutively enrolled at INCA between January 2010 and December 2014 that were submitted to neoadjuvant chemotherapy and subsequently operated.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response Rate
Time Frame: 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.
From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Objective response rate
Time Frame: 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.
From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks
Determine predictive markers
Time Frame: Approximately 24 weeks: from diagnosis up to surgery.
To determine predictive markers for sensitivity and resistance to chemotherapy.
Approximately 24 weeks: from diagnosis up to surgery.
Determine prognostic markers
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Cancer, Brazil

Investigators

  • Principal Investigator: Jesse L da Silva, MD, Instituto Nacional de Câncer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2010

Primary Completion (Actual)

December 31, 2014

Study Completion (Actual)

December 31, 2014

Study Registration Dates

First Submitted

May 4, 2018

First Submitted That Met QC Criteria

May 25, 2018

First Posted (Actual)

May 30, 2018

Study Record Updates

Last Update Posted (Actual)

May 31, 2018

Last Update Submitted That Met QC Criteria

May 29, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TNBCbrazil

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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