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

Recruiting
Conditions
Breast Cancer
Interventions
Procedure: skin punch biopsy
Registration Number
NCT02772367
Lead Sponsor
Memorial Sloan Kettering Cancer Center
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
120
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.
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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
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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Breast Cancer Patientsskin punch biopsyIn 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.
Primary Outcome Measures
NameTimeMethod
derive iPSs from skin fibroblasts1 day

described by Yamanaka et al with modification using the Millipore STEMCCA excisable polycystronic lentivirus reprogramming kit.2

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

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