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This pilot study involves very frequent monitoring of breast cancer patient blood levels of hs-cTnT Troponin and n-t-BNP (Brain Natriuretic Peptide) before and after initiation of chemotherapy with either adriamycin or trastuzumab in order to define the kinetics of both biomarkers during the first two cycles of chemotherapy. Cardiac troponins and BNP are frequently elevated after experimental chemotherapy in animal models. Their behavior in humans has been inconsistent, with occasional elevations seen, usually within 30 days of therapy. Assays for troponin with sensitivity into the pg/ml range have now been introduced. A majority of patients greater than age 50 have elevations above the detection limit, compared to only 1-3% with conventional troponin assays, and over 90% of diabetics have elevations above the detection limit. Moreover, augmented release of high sensitivity troponin is detected after exercise or rapid atrial pacing of durations of 10-15 minutes in patients with and without coronary artery disease. This improved sensitivity suggests the potential for detection and monitoring of cardiac damage after cancer chemotherapy. We hypothesized that this new generation of troponin assay would be associated with kinetic behavior suggesting ongoing cardiac damage with anthracycline therapy, and possibly also with trastuzumab.
Collect blood samples in two groups of patients (n=10 per group) for amino-terminal brain natriuretic peptide (n-t-BNP) and high sensitivity cardiac troponin T (hs-cTnT):
Blood samples for hs-cTNT and n-t-BNP will be obtained on days pre-treatment, and post-treatment days 1, 2, 3, 7, pre-cycle 2, and post-cycle 2 days 1,2,3 and 7. The interval for treatment is usually two weeks for adriamycin and three weeks for trastuzumab. We will identify frequency of detectible levels above the detection limit and above the baseline, peak values and area under the curve. Enrollment of up to 15 per group will be allowed to guarantee acquisition of 10 full sets of samples. Lab draw from chemotherapy ports will be allowed. We plan to store specimens for future analyses with more sensitive assays in development.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Patients with breast cancer beginning chemotherapy with a dose-dense regimen including adriamycin without concurrent trastuzumab. | ||
| Group 2 | Patients receiving trastuzumab in the adjuvant, neo-adjuvant, or metastatic setting in a regimen not containing simultaneous adriamycin therapy. |
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| Measure | Description | Time Frame |
|---|---|---|
| Area under the curve | Concentration-time plots from pre-treatment through days 1,2,3,7,and pre-cycle two | one year |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline to peak | The difference between the pretreatment value and the highest level on days 1,2,3 or 7 | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Descriptive statistics | Descriptive statistics will be used to describe the quantitative values, and frequencies above and below the detection limit, time to peak, and amplitude of peak versus baseline values for both n-t-BNP and hs-cTnT. | 1 year |
Inclusion Criteria:
Exclusion Criteria:
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Mayo Clinic Florida female, adult patients from Hematology/Oncology Department undergoing clinically-indicated treatment for breast cancer which includes either, but not both, adriamycin or trastuzamab will be eligible to participate
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| Name | Affiliation | Role |
|---|---|---|
| Joseph L Blackshear, M.D. | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Jacksonville | Florida | 32224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28704807 | Result | Advani P, Hoyne J, Moreno-Aspita A, Dubin M, Brock S, Harlow C, Chumsri S, Suter T, Blackshear JL. High-Sensitivity Troponin T and NT-proBNP Kinetics in Breast Cancer Chemotherapy. Chemotherapy. 2017;62(6):334-338. doi: 10.1159/000477797. Epub 2017 Jul 14. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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Whole blood 10 ml per draw, yielding 5 ml of serum. After testing, the remaining serum will be stored.
| D017437 |
| Skin and Connective Tissue Diseases |