Background: Breast cancer is the leading cause of cancer in women, with 1.8 million patients diagnosed globally each year. In early stage disease, anthracycline regimens are commonly employed, but the risk of cardiotoxicity is high. Replacing anthracyclines with taxanes in combination with cyclophosphamide may improve response  and Bevacizumab (BVZ) may provide addtional benefit. However, as BVZ can cause hypertension and increased risk of cardiac failure, a rationale exists for studying biomarkers of cardiotoxicity in this setting.
Methods: We assessed a panel of biomarkers in n = 57 early stage breast cancer patients whom underwent docetaxel/cyclophosphamide/BVZ therapy on the TC-Avastin Trial (NCT00911716). Serum was collected prior to treatment and at 3 months. Cardiotoxicity was defined as decline in left ventricular ejection fraction ≥ 10% to <55% over 1 year treatment + 2 year follow-up. Cardiac troponin I and T [cTnI, cTnT], Endothelin-1, Galectin-3, Placental Growth Factor [PlGF], Platelet Derived Growth Factor, Vascular Endothelial Growth Factor receptors 1 and 2, total nitrous oxide NO and myeloperoxidase [MPO]) were screened by ELISA in a subgroup (n = 16). Pilot and recently published findings  implicated PlGF, cTn1 and MPO, which were subsequently assessed in the larger cohort.
Results: Changes in serum MPO or cTnI were not related to cardiotoxicity when analysed in the larger cohort. However, a “cut-off” PlGF fold change of 0.99 could differentiate patients who developed cardiotoxicity from those that did not. 74% of cardiotoxicity patients, compared to only 35% of non-cardiotoxicity fell below the 0.99 cut-off. Conversely, 65% of non-cardiotoxicity patients, compared to 25% of cardiotoxicity patients fell above the cut-off (p = 0.0042).
Conclusions: Our data suggest that decreased PlGF at 3 months may predict cardiotoxicity. These observations require further validation.
This work was funded by AngioTox, an EC FP7 IAPP Marie Curie Award (Grant Agreement 251528). Jones et al., J. Clin. Oncol.27, 1177-1183 (2009);  Putt et al., Clin. Chem 61, 1164-1172 (2015).
Citation Format: David W. Murray, Alice C. O’Farrell, Giuseppe Gullo, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Bonnie Ky, William M. Gallagher, Norma O’Donovan, John Crown, Annette T. Byrne. Analysis of putative serum biomarker candidates for cardiotoxicity prediction in a cohort of early stage breast cancer patients treated with docetaxel, cyclophosphamide, and bevacizumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1828.