Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation.
OBJECTIVE
Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated.


METHODS
In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%.


RESULTS
TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001).


CONCLUSIONS
TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.
Cardinale
Daniela
D
Cardiology Unit, European Institute of Oncology, Milan, Italy. daniela.cardinale@ieo.it
Colombo
Alessandro
A
Torrisi
Rosalba
R
Sandri
Maria T
MT
Civelli
Maurizio
M
Salvatici
Michela
M
Lamantia
Giuseppina
G
Colombo
Nicola
N
Cortinovis
Sarah
S
Dessanai
Maria A
MA
Nolè
Franco
F
Veglia
Fabrizio
F
Cipolla
Carlo M
CM
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D000068878:Trastuzumab; D016896:Treatment Outcome; D019210:Troponin I / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019210:Troponin I; D000068878:Trastuzumab