Trastuzumab induced cardiotoxicity in HER2 positive breast cancer patients attended in a tertiary hospital

Ayres, Lorena Rocha; Campos, Marília Silveira de Almeida; Gozzo, Thaís de Oliveira; Martinez, Edson Zangiacomi; Ungari, Andrea Queiróz; Andrade, Jurandyr Moreira de; Pereira, Leonardo Régis Leira

doi:10.1007/s11096-015-0070-y

Cited by 21 publications

(24 citation statements)

References 29 publications

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“…Based on these results, trastuzumab has become the standard of care for the treatment of HER2-positive early-stage breast cancer in the adjuvant setting. Although generally well tolerated, an important issue of concern regarding trastuzumab is cardiac toxicity, which can lead to treatment discontinuation, thus depriving patients of therapeutic benefits [45]. In particular, trastuzumab-induced cardiac toxicity often develops when combined with chemotherapy such as doxorubicin and epirubicin, agents with documented dose-related cardiac toxicity that can lead to chronic heart failure, reduced quality of life, and even death [678].…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab

et al. 2017

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PurposeWe intended to determine whether dexrazoxane (DZR) is cardioprotective during administration of adjuvant anthracycline-based chemotherapy followed by a 1-year trastuzumab treatment.MethodsThe medical records of 228 patients who underwent surgical resection and received adjuvant chemotherapy with trastuzumab for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer between January 2010 and December 2014 were reviewed. Approximately 25% of patients received DZR prior to each administration of doxorubicin during doxorubicin with cyclophosphamide (AC) chemotherapy. DZR was not administered during the 1-year trastuzumab maintenance period. Rates of cardiac events (reduction in left ventricular ejection fraction [LVEF] by 10% or more; reduction in absolute LVEF to <45%) and cardiac event-free duration (CFD) were examined. The trastuzumab interruption rate was also assessed.ResultsTwelve percent of patients experienced a cardiac event. Repeated-measures analysis of variance for ejection fraction revealed a significant main effect of time, and a significant group (DZR)×time interaction. The group treated with adjuvant chemotherapy and DZR experienced significantly lower frequencies of cardiac events than the adjuvant chemotherapy only group. In multivariate analysis, DZR administration was associated with significantly fewer cardiac events. Moreover, DZR administration was an independent good prognostic factor for CFD. Only one patient (2.3%) experienced early interruption of trastuzumab in the adjuvant chemotherapy with DZR group due to cardiac toxicity, whereas 10 patients (7.6%) experienced a trastuzumab stop event in the adjuvant chemotherapy only group.ConclusionDZR is cardioprotective in HER2-positive breast cancer patients who received adjuvant chemotherapy with trastuzumab. A large cohort randomized trial is needed to determine if DZR has an effect on trastuzumab interruption and completion of 12-month trastuzumab. Because cardiac toxicity has a significant negative effect on trastuzumab maintenance and quality of life, DZR administration could be considered concomitantly with anthracycline-based adjuvant chemotherapy with trastuzumab.

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Section: Introductionmentioning

confidence: 99%

Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab

et al. 2017

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“…5,21 Nevertheless, in the prospective study performed in Poland and in Brazilian retrospectives studies, no risk factor was associated with the development of trastuzumab-related cardiotoxicity. 3,4,22 It is noteworthy that this cohort seems to have a higher incidence of cardiotoxicity in the metastatic setting than studies performed in other countries despite their similar incidence of comorbidities. One point which might be considered is that genetic variants could also play a role in the development of cardiotoxicity in breast cancer patients.…”

Section: Discussionmentioning

confidence: 63%

“…Symptomatic HF events (New York Heart Association [NYHA] functional class III/IV) were experienced by 6.2% of EBC patients, which was similar to the incidence observed in clinical trials (range from 1.2 to 14.2%) 1,[16][17][18][19] and also to one retrospective Brazilian study (incidence of 6.3%). 3 The incidence of trastuzumab-related LVEF dysfunction during metastatic treatment has usually been reported higher than in adjuvant setting. The incidence of symptomatic and asymptomatic cardiac dysfunction in MBC patients was 75%, which was higher than the one reported by Slamon et al, in a phase III trial (27%) 2 and two other retrospective observational studies from United Kingdom and the USA (incidence of 13.1% and 34.2%, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…In reallife settings, observational studies have shown a higher incidence than those reported in clinical trials. [3][4][5][6] The cardiotoxicity associated with trastuzumab is mostly reversible; nevertheless, in some cases, it could lead to severe heart failure (HF) and death. 7 To the best of our knowledge, no studies have measured in a prospective way the incidence of trastuzumab-related cardiotoxicity (TRC) in Brazilian patients with early and metastatic HER-2 positive breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Observational study of trastuzumab-related cardiotoxicity in early and metastatic breast cancer

Grazziotin

Picon

2016

J Oncol Pharm Pract

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Introduction Trastuzumab-related cardiotoxicity has been a major concern in clinical practice, since observational studies have shown higher incidences than that reported in clinical trials. We aim to measure the incidence of trastuzumab-related cardiotoxicity in patients with early and metastatic breast cancer in the south of Brazil. Methods Multicenter prospective observational study, which included 109 patients with early or metastatic HER-2+ breast cancer undergoing any trastuzumab-based regimen. Cardiac events were measured by transthoracic echocardiography assessments and by signs and symptoms of heart failure. Results Trastuzumab-related cardiotoxicity was observed in 58 patients (53.2%). Emergency and hospitalization admissions were necessary in seven and three patients, respectively, due to symptoms of heart failure. One patient died in consequence of trastuzumab-related cardiotoxicity. In total, trastuzumab was discontinued in 31.2% of patients, of which almost a third could not return to treatment. In this study, no risk factors were significantly associated with the development of cardiotoxicity. Discussion The incidence of TRC and trastuzumab's early discontinuation observed was significantly higher in comparison with other studies. These findings endorse the fact that trastuzumab-related cardiotoxicity is a relevant adverse reaction, and therefore, cardiac dysfunction's monitoring must be highlighted in order to allow a safe use of trastuzumab in this population.

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“…A different form of cardiac toxicity that is, in most cases, reversible can be caused by the monoclonal antibody trastuzumab, which causes a condition of frozen myocardium; discontinuing the drug reverses the effect. 41 Risk of cardiac toxicity with trastuzumab also increases with age, and management consists of suspending the administration of trastuzumab, although the drug may be safely restarted when myocardial function has been restored.…”

Section: Treatment-related Complicationsmentioning

confidence: 99%

Palliative Care in Older Patients with Cancer

2015

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The scope of palliative care encompasses more issues that symptom management and, for this reason, palliative care should be provided once the diagnosis of cancer is established. Determining treatment goals is essential to improve the treatment experience. Symptom management is similar in older and young patients, but symptoms in the older population may be associated with more frequent and severe complications. Many options exist to prevent and ameliorate the complications of oncology treatment in the aged. However, more studies should be conducted on the long-term care of older patients who have survived cancer.

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Trastuzumab induced cardiotoxicity in HER2 positive breast cancer patients attended in a tertiary hospital

Cited by 21 publications

References 29 publications

Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab

Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab

Observational study of trastuzumab-related cardiotoxicity in early and metastatic breast cancer

Palliative Care in Older Patients with Cancer

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