Generation of Heart Muscle Cells From Blood or Skin Cells of Breast Cancer Patients

Generation of Induced Pluripotent Stem Cell Derived Cardiomyocytes From Patients Exposed to Trastuzumab Therapy for Breast Cancer

The purpose of this study is to investigate whether cells from a biopsy taken from the patient skin can be transformed into cardiomyocytes the changes in cardiomyocyte (heart muscle cells) when grown in a special culture medium outside of the body. The structure and function of these cells will then be studied to determine why some patients with breast cancer who are treated with chemotherapy including anthracycline (e.g. Doxorubicin) and anti-HER2 therapy (e.g. Herceptin) develop decreased heart function.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: skin punch biopsy

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Angel Chan, MD, PhD; Phone Number: 212-639-7217; Email: chana5@mskcc.org
• Study Contact Backup: Name: Richard Steingart, MD; Phone Number: 212-639-8488

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center
      • Contact: Angel Chan, MD, PhD; Phone Number: 212-639-7217

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Potential research subjects will be identified by a member of the patient's treatment team, the protocol investigator, or research team at Memorial Sloan Kettering Cancer Center (MSKCC).

Description

Inclusion Criteria:

• Female
• Age greater than 18 years
• Willing to participate in protocol procedures with signed informed consent
• Assessment of LVEE via echocardiogram, cardiac MRI, or MUGA

Subjects in the cardiotoxicity group (TOX) must meet the following criteria:

• History of HER2 positive breast cancer (stage I-IV)
• Prior/current treatment with anthracycline based chemotherapy followed by anti-HER2 directed therapy or anti-HER2 directed therapy alone
• Assessment of LVEF at baseline prior to initiation of anthracycline or anti-HER2 therapy and during anti-HER2 therapy via echocardiogram, cardiac MRI, or MUGA
• Prior confirmed diagnosis of cardiotoxicity associated with anti-HER2 based therapy, defined as a decrease in LVEF > 10% from baseline to < 53% with symptoms of heart failure (NYHA class II-IV).

Subjects in the no cardiotoxicity group (NO-TOX) must meet the following criteria:

• History of HER2 positive breast cancer (stage I-IV)
• Completion of planned anthracycline and anti-HER2 therapy, or anti-HER2 therapy alone
• No symptoms of heart failure (NYHA class II-IV) during and at the end of anthracycline and anti-HER2 therapy
• Assessment of LVEF at baseline prior to innitiation of anthracycline or anti-HER2 therapy and during anti-HER2 therapy via echocardiogram, cardiac MRI, or MUGA
• Normal LVEF >53% at each assessment during and at the end of trastuzumab therapy.
• Maximum absolute decrease in LVEF <5% from baseline during and at the end of trastuzumab therapy.
• LVEF assessment performed at baseline and at least two time points during trastuzumab therapy.

Exclusion Criteria:

• Unwilling or unable to give skin biopsies
• Contraindications to punch biopsy including but not limited to bleeding diathesis, as determined by the investigator.

• Known pre-existing CV disease prior to initiation of breast cancer therapy as determined by the investigator, including

  • Obstructive coronary artery disease (stenosis >70%)
  • Arrhythmia - paroxysmal or persistent atrial arrhythmias, sustained ventricular tachycardia (>30 seconds), ventricular fibrillation, or cardiac arrest
  • Cardiomyopathy (EF <53%)
  • Heart failure (NYHA class II-IV)
  • Valvular heart disease with equal to or greater than moderate stenosis or regurgitation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breast Cancer Patients; In study participants undergoing breast reconstruction surgery prior to breast radiation therapy, we will obtain skin tissue at the time of reconstruction surgery from the surgical specimen.	Procedure: skin punch biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
derive iPSs from skin fibroblasts	described by Yamanaka et al with modification using the Millipore STEMCCA excisable polycystronic lentivirus reprogramming kit.2	1 day

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Angel Chan, MD, PhD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2016
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimated): May 13, 2016

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: cardiotoxicity; 16-025
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 16-025