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
Sub-type Article (original research)
DOI 10.1007/s10549-012-2039-z
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
Collection year 2013
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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