Genetics and Heart Health After Cancer Therapy

NCT03510689 | Completed DMC

• 1 other identifier: UPCC 13117
• Study Type: observational
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this study is to use patient-centered in vitro and in vivo models to answer the fundamental question of whether or not pathogenic mutations in BRCA1/2 result in an increased risk of CV disease

Conditions

Breast Cancer; Hereditary Breast/Ovarian Cancer (brca1, Brca2); Heart Diseases; Drug-Induced Cardiomyopathy

Keywords

Cardio-oncology

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Ejection Fraction

  6 years

Study Arms (3)

Group 1

Subjects with genetic testing confirming deleterious mutations in BRCA1 or BRCA2 whose prior treatment for breast cancer includes anthracycline exposure. All groups have same schedule of study procedures, including echocardiography, cardiopulmonary exercise testing, and blood collection.

Diagnostic Test: echocardiography; Other: Cardiopulmonary Exercise Testing; Other: Blood Collection

Group 2

Subjects with genetic testing confirming deleterious mutations in BRCA1 or BRCA2 whose prior treatment for breast cancer does not include anthracycline exposure. All groups have same schedule of study procedures, including echocardiography, cardiopulmonary exercise testing, and blood collection.

Diagnostic Test: echocardiography; Other: Cardiopulmonary Exercise Testing; Other: Blood Collection

Group 3

Subjects with genetic testing confirming no mutation in BRCA1 or BRCA2 whose prior treatment for breast cancer includes anthracycline exposure. All groups have same schedule of study procedures, including echocardiography, cardiopulmonary exercise testing, and blood collection.

Diagnostic Test: echocardiography; Other: Cardiopulmonary Exercise Testing; Other: Blood Collection

Interventions

echocardiography DIAGNOSTIC_TEST

Resting echocardiograms (Vivid E9 or E95, GE Healthcare) with conventional measures of systolic and diastolic function, in conjunction with posthoc quantitation of novel measures of strain and strain rate will be obtained at each study time point.

Group 1; Group 2; Group 3

Cardiopulmonary Exercise Testing OTHER

A cardiopulmonary exercise test (CPET, also called V02 test) will be completed at each study time point utilizing a standard clinical protocol, on either a stationary bike or treadmill. The purpose of this test is to estimate maximal oxygen consumption (V02 max) as in index of cardiopulmonary fitness. Resting ECG, heart rate, and BP will be obtained prior to beginning the test, during each stage of the test and for 5 minutes after the test is stopped.

Group 1; Group 2; Group 3

Blood Collection OTHER

We will obtain blood samples (approximately 16mL) at baseline and (approximately 12mL) at each follow-up visit. Typically these will be drawn via peripheral venipuncture, however if patients have a port-a-cath in place, blood may be drawn from the port instead.

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Initial diagnosis of Breast Cancer in 2005 or later BRCA testing documenting either germline mutation in BRCA1/BRCA2 or no mutation in BRCA1/2.

You may qualify if:

• ≥18 years of age
• Initial diagnosis of Breast Cancer in 2005 or later
• Documented BRCA testing (results from a local laboratory are acceptable) showing
• confirmation of a germline mutation in BRCA1 or BRCA2 that is predicted or suspected to be deleterious OR
• confirmation that no mutation was detected in BRCA1 or BRCA2
• Non-carriers will have been treated with an anthracycline-based chemotherapy regimen; carriers may or may not have been treated with an anthracycline-based chemotherapy regimen.
• Approximately at least 12 months from initiation of adjuvant treatment or neo-adjuvant chemotherapy
• Able to provide informed consent

You may not qualify if:

• Stage IV Breast Cancer
• Genetic testing confirming a variant of unknown significance (VUS) or benign polymorphism in BRCA1 or BRCA2
• V02 Testing contraindicated for any reason, including:
• Myocardial infarction (within past 3 months)
• High-risk unstable angina;
• High-risk or uncontrolled cardiac arrhythmias;
• Symptomatic severe aortic stenosis;
• Uncontrolled symptomatic heart failure;
• Acute pulmonary embolus or pulmonary infarction;
• Acute myocarditis or pericarditis;
• Acute aortic dissection;
• Coronary revascularization procedure within the past three months;
• Uncontrolled hypertension, defined as systolic blood pressure ≥ 180mmHg or diastolic blood pressure ≥ 100mmHg;
• Clinically significant valvular heart disease (severe stenosis or regurgitation);
• Known aortic aneurysm; or

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Hereditary Breast and Ovarian Cancer Syndrome; Heart Diseases

Interventions

Echocardiography; Exercise Test; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplastic Syndromes, Hereditary; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Gonadal Disorders; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative

Study Officials

• Bonnie Ky, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: April 27, 2018
• Study Start: December 5, 2017
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: October 16, 2024

Record last verified: 2024-10

Locations

US (1)