High-sensitivity C-reactive protein (hs-CRP) as a biomarker for trastuzumab-induced cardiotoxicity in HER2-positive early-stage breast cancer: A pilot study

Onitilo, Adedayo A., Engel, Jessica M., Stankowski, Rachel V., Liang, Hong, Berg, Richard L. and Doi, Suhail A. R. (2012) High-sensitivity C-reactive protein (hs-CRP) as a biomarker for trastuzumab-induced cardiotoxicity in HER2-positive early-stage breast cancer: A pilot study. Breast Cancer Research and Treatment, 134 1: 291-298. doi:10.1007/s10549-012-2039-z


Author Onitilo, Adedayo A.
Engel, Jessica M.
Stankowski, Rachel V.
Liang, Hong
Berg, Richard L.
Doi, Suhail A. R.
Title High-sensitivity C-reactive protein (hs-CRP) as a biomarker for trastuzumab-induced cardiotoxicity in HER2-positive early-stage breast cancer: A pilot study
Journal name Breast Cancer Research and Treatment   Check publisher's open access policy
ISSN 0167-6806
1573-7217
Publication date 2012-07-01
Sub-type Article (original research)
DOI 10.1007/s10549-012-2039-z
Open Access Status Not yet assessed
Volume 134
Issue 1
Start page 291
End page 298
Total pages 8
Place of publication New York, NY, United States
Publisher Springer New York
Language eng
Abstract Monitoring of left ventricular ejection fraction (LVEF) is the current standard for detection of trastuzumab-induced cardiotoxicity; however, time-to-diagnosis and cost of assessment are suboptimal in women with early-stage breast cancer. We assessed the utility of B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin I (cTnI) as serum biomarkers for early detection of trastuzumab-induced cardiotoxicity. Fifty-four women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were prospectively enrolled, and the relationship between elevated serum BNP, hs-CRP, and cTnI levels and clinically significant decreases in LVEF was examined. LVEF was monitored at 3-4 month intervals during trastuzumab treatment. Laboratory testing for candidate biomarkers was repeated every 3 weeks with each cycle of trastuzumab. Trastuzumab-induced cardiotoxicity was defined as a decrease in LVEF of >15 % or to a value below 50 %. A clinically significant decrease in LVEF was observed in 28.6 % of women. Abnormal hs-CRP (>3 mg/L) predicted decreased LVEF with a sensitivity of 92.9 % (95 % CI 66.1-99.8) and specificity of 45.7 % (95 % CI 28.8-63.4), and subjects with normal hs-CRP levels (<3 mg/L) have 94.1 % negative predictive 94.1 % (95 % CI 70.3-99.9) suggesting that normal hs-CRP levels may be associated with low future risk for decreased LVEF; however, no association with BNP or cTnI was observed. A false positive would have a relatively low associated cost in breast cancer patients undergoing adjuvant trastuzumab therapy and would indicate continuation of routine observation during treatment through traditional means. The maximum hs-CRP value was observed a median of 78 days prior to detection of cardiotoxicity by decreased LVEF, and those with normal levels were at lower risk for cardiotoxicity. Regular monitoring of hs-CRP holds promise as a biomarker for identifying women with early-stage breast cancer at low risk for asymptomatic trastuzumab-induced cardiotoxicity. To our knowledge, this is the first study documenting the utility of a less expensive, reproducible, easily obtainable biomarker with rapid results for evaluating cardiotoxicity related to trastuzumab therapy.
Keyword Antibodies, Monoclonal/therapeutic use
Breast neoplasms/metabolism/mortality
Heart diseases/chemically induced
hs-CRP
Receptor, HER2
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Public Health Publications
 
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