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

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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.

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Acknowledgments

The authors thank Marie Fleisner of the Marshfield Clinic Research Foundation’s Office of Scientific Writing and Publication for proofreading/copyediting assistance. Funding for this study was provided by the Marshfield Clinic Physician Research Funds and the Marshfield Clinic Research Foundation Disease Specific Funds.

Conflicts of interest

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Marshfield Clinic Weston Center, 3501 Cranberry Boulevard, Weston, WI, 54476, USA

    Adedayo A. Onitilo

  2. Marshfield Clinic Research Foundation, Marshfield, WI, USA

    Adedayo A. Onitilo & Rachel V. Stankowski

  3. Clinical Epidemiology Unit, School of Population Health, University of Queensland, Brisbane, QLD, Australia

    Adedayo A. Onitilo & Suhail A. R. Doi

  4. Department of Hematology/Oncology, Marshfield Clinic Cancer Care at St Michaels, Stevens Point, WI, USA

    Jessica M. Engel

  5. Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA

    Hong Liang & Richard L. Berg

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  1. Adedayo A. Onitilo
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Correspondence to Adedayo A. Onitilo.

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Onitilo, A.A., Engel, J.M., Stankowski, R.V. et al. 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 Res Treat 134, 291–298 (2012). https://doi.org/10.1007/s10549-012-2039-z

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  • DOI: https://doi.org/10.1007/s10549-012-2039-z

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