Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06)

Breast Cancer Res Treat. 2018 Apr;168(3):631-638. doi: 10.1007/s10549-017-4628-3. Epub 2017 Dec 27.

Abstract

Background: Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients.

Methods: This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel.

Results: 173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2.

Conclusion: These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

Keywords: Brain natriuretic peptide; Cardiotoxicity; HER2 positive breast cancer; Lapatinib; Troponin T.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cardiotoxicity / blood*
  • Cardiotoxicity / pathology
  • Cardiovascular Abnormalities / blood*
  • Cardiovascular Abnormalities / chemically induced
  • Cardiovascular Abnormalities / pathology
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Lapatinib / administration & dosage
  • Lapatinib / adverse effects
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Receptor, ErbB-2 / genetics
  • Trastuzumab / administration & dosage
  • Trastuzumab / adverse effects
  • Troponin T / blood

Substances

  • Biomarkers
  • Troponin T
  • Lapatinib
  • Natriuretic Peptide, Brain
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Paclitaxel