Long-Term Risk of Heart Failure in Breast Cancer Patients After Adjuvant Chemotherapy With or Without Trastuzumab.
OBJECTIVES
This study sought to evaluate the long-term risk of developing heart failure (HF) in patients receiving trastuzumab therapy.


BACKGROUND
Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. The long-term risk of HF is less well described.


METHODS
In a nationwide Danish retrospective cohort study, 9,901 patients scheduled for adjuvant treatment for early-stage breast cancer were identified in the Danish Breast Cancer Cooperative Group database. Of these, 8,812 patients (25% HER2-positive; 51.7 ± 8.5 years of age) received chemotherapy including anthracycline; and if they were HER2 positive, trastuzumab was added. The primary endpoint was a diagnosis of HF assessed before and after 18 months in a landmark analysis to distinguish short- and long-term risks.


RESULTS
Median follow-up was 5.4 years (interquartile range [IQR]: 4.1 to 6.8 years). In the trastuzumab group, 60 patients had HF by 9 years versus 51 in the group who were treated with chemotherapy alone, corresponding to incidence rates per 1,000 patient years of 5.3 (95% confidence interval [CI]: 4.1 to 6.8) versus 1.4 (95% CI: 1.1 to 1.8), respectively. The cumulative incidence of HF was higher in the trastuzumab group at both the short- and long-term (p < 0.01), yielding adjusted hazard ratios of 8.7 (95% CI: 4.6 to 16.5; p < 0.01) for early HF and 1.9 (95% CI: 1.2 to 3.3; p = 0.01) for late HF associated with trastuzumab treatment.


CONCLUSIONS
Trastuzumab treatment is associated with a 2-fold increased risk of late HF compared with chemotherapy treatment alone.
['Banke|Ann|A|', 'Fosbøl|Emil L|EL|', 'Ewertz|Marianne|M|', 'Videbæk|Lars|L|', 'Dahl|Jordi S|JS|', 'Poulsen|Mikael Kjær|MK|', 'Cold|Søren|S|', 'Jensen|Maj-Britt|MB|', 'Gislason|Gunnar H|GH|', 'Schou|Morten|M|', 'Møller|Jacob E|JE|']
D000328:Adult D000368:Aged D000074322:Antineoplastic Agents, Immunological D000971:Antineoplastic Combined Chemotherapy Protocols D001943:Breast Neoplasms D018270:Carcinoma, Ductal, Breast D066126:Cardiotoxicity D017024:Chemotherapy, Adjuvant D015331:Cohort Studies D003520:Cyclophosphamide D003718:Denmark D000077143:Docetaxel D015251:Epirubicin D005260:Female D006333:Heart Failure D006801:Humans D015994:Incidence D008137:Longitudinal Studies D015412:Mastectomy, Segmental D008875:Middle Aged D018719:Receptor, ErbB-2 D012189:Retrospective Studies D012306:Risk D013318:Stroke Volume D000068878:Trastuzumab
heart failure trastuzumab breast cancer cardiotoxicity epidemiology