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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Left Ventricular Ejection Fraction | 6 years |
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Inclusion Criteria
≥18 years of age
Initial diagnosis of Breast Cancer in 2005 or later
Documented BRCA testing (results from a local laboratory are acceptable) showing
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
Exclusion Criteria
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:
Women who are pregnant
Any other clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
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Initial diagnosis of Breast Cancer in 2005 or later BRCA testing documenting either germline mutation in BRCA1/BRCA2 or no mutation in BRCA1/2.
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| Name | Affiliation | Role |
|---|---|---|
| Bonnie Ky, MD | Abramson Cancer Center at Penn Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D061325 | Hereditary Breast and Ovarian Cancer Syndrome |
| D006331 | Heart Diseases |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D004452 | Echocardiography |
| D005080 | Exercise Test |
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D057791 | Cardiac Imaging Techniques |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| 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. |
|
| 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. |
|
| D017437 |
| Skin and Connective Tissue Diseases |
| D010051 | Ovarian Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D009386 | Neoplastic Syndromes, Hereditary |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D002318 | Cardiovascular Diseases |
| D014463 | Ultrasonography |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D012129 | Respiratory Function Tests |
| D003948 | Diagnostic Techniques, Respiratory System |
| D016552 | Ergometry |
| D008919 | Investigative Techniques |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |