Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors

Farolfi, Alberto; Melegari, Elisabetta; Aquilina, Michele; Scarpi, Emanuela; Ibrahim, Toni; Maltoni, Roberta; Sarti, Samanta; Cecconetto, Lorenzo; Pietri, Elisabetta; Ferrario, Cristiano; Fedeli, Anna; Faedi, Marina; Nanni, Oriana; Frassineti, Giovanni Luca; Amadori, Dino; Rocca, Andrea

doi:10.1136/heartjnl-2012-303151

Cited by 99 publications

(80 citation statements)

References 29 publications

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“…Past use of anthracyclines, especially at high cumulative doses (>250 mg/m 2 of doxorubicin or >600 mg/m 2 of epirubicin),53 appears to be the most important risk factor for subsequent cardiac dysfunction 49. In 1 retrospective analysis, past anthracycline use was the only significant predictor of trastuzumab‐induced cardiotoxicity 54. Additionally, concomitant use of anthracycline or short period (3 weeks versus 3 months) between anthracycline use and administration of trastuzumab appear to increase the risk of cardiac adverse events in some studies 14, 55.…”

Section: Risk Factors For Cardiotoxicity Associated With Her2 Targetementioning

confidence: 99%

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Florido

Smith

Cuomo

et al. 2017

JAHA

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Section: Risk Factors For Cardiotoxicity Associated With Her2 Targetementioning

confidence: 99%

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Florido

Smith

Cuomo

et al. 2017

JAHA

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“…It did not include patients with reduced cardiac function at baseline and identified coronary artery disease, atrial fibrillation, hypertension, diabetes mellitus, chronic kidney disease, aged >74 years, and administration of other chemotherapy as risk factors 28. Other retrospective cohort studies, not limited to a Medicare population but including patients of all ages, were unable to identify any predictors for TIC other than >240 mg/m 2 doxorubicin exposure 9, 29. However, this has also not been consistently seen as a risk factor.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, the HERA (HERceptin Adjuvant) trial showed an HF incidence of only 0.8% and decreases in LVEF of ≥10% from baseline to an LVEF of <50% in only 7.2% of patients 34. In contrast, real world cohort studies noted a decline in LVEF by ≥10% points in 15% to 40% of patients 9, 29. The current study is in agreement with these previous reports.…”

Section: Discussionmentioning

confidence: 99%

“…Adverse events typically associated with chemotherapy, such as alopecia, myelosuppression, and nausea and vomiting are not seen with trastuzumab. Cardiotoxicity, either leading to an asymptomatic decrease in left ventricular ejection fraction (LVEF) or heart failure (HF), remains the most important adverse effect 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16…”

Section: Introductionmentioning

confidence: 99%

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Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

Nowsheen

Aziz

Park

et al. 2018

JAHA

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BackgroundTrastuzumab is life‐extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 (HER2+), but has known cardiotoxic risk. We sought to determine if trastuzumab can be administered to patients with reduced baseline cardiac function at no higher cardiotoxicity risk than in those with normal cardiac function at baseline.Methods and ResultsWe performed a retrospective study of women treated with trastuzumab for human epidermal growth factor receptor 2 breast cancer at Mayo Clinic Rochester between January 1, 2000 and August 31, 2015 with pre‐ and on‐therapy echocardiograms available for review. A left ventricular ejection fraction (LVEF) <53% was considered abnormal, and a ≥10% decline in LVEF as evidence of cardiotoxicity based on the criteria of the American Society of Echocardiography. A total of 428 women were identified; 408 had a normal cardiac function (LVEF 63.4±5%) and 20 had an impaired cardiac function (LVEF 45.4±7%) before trastuzumab. Seven women (35%) with reduced LVEF at baseline had a ≥10% reduction in LVEF, compared with 179 (43.9%) of those with normal LVEF before trastuzumab initiation (P=NS). Symptomatic heart failure developed more often in patients with reduced versus normal baseline LVEF (25% versus 4.2%, P<0.05). After adjusting for patient age and breast cancer disease stage, survival rates over 5 years from time of diagnosis were found to be lower for patients with reduced baseline LVEF compared with patients with normal baseline LVEF (P<0.001); the adjusted proportion of patients surviving at 5 years for those with low LVEF at baseline was 79% and for those with normal LVEF was 93%.ConclusionsWomen undergoing trastuzumab therapy for breast cancer with impaired baseline cardiac function experience no higher risk of LVEF decline, but more frequently develop symptomatic heart failure. While trastuzumab could be considered, these patients should be co‐managed by a cardiologist.

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“…It has also been seen that cardiac side-effects may occur after adjuvant treatment with trastuzumab, with an absolute 12.0% higher adjusted incidence rate for heart failure over 3 years (2). Although preclinical data originally pointed towards a radiosensitizing effect of trastuzumab, more recent clinical studies have demonstrated that concurrent RT and trastuzumab for EBC is not associated with increased acute adverse events, including those of a cardiological nature (3,4).…”

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The impact of radiotherapy, trastuzumab and hormonal therapy on cardiac fibrosis. More is worse?

Farolfi¹

2014

Anadolu Kardiyol Derg

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The impact of radiotherapy, trastuzumab and hormonal therapy on cardiac fibrosis. More is worse?334 Radiotherapy (RT) for early breast cancer (EBC) has proven capable of reducing the rates of recurrence and death from the disease. Similarly, trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) antibody, has significantly improved the prognosis of breast cancer patients in both the adjuvant and metastatic settings. However, major concerns have arisen about these treatments because both have been linked to cardiac toxicity, the former increasing the risk of ischemic heart disease, the latter, heart failure.Before the era of 3-dimensional CT-based treatment planning it was observed that rates of major coronary events increased linearly for the first 5 years after radiotherapy (1). It has also been seen that cardiac side-effects may occur after adjuvant treatment with trastuzumab, with an absolute 12.0% higher adjusted incidence rate for heart failure over 3 years (2). Although preclinical data originally pointed towards a radiosensitizing effect of trastuzumab, more recent clinical studies have demonstrated that concurrent RT and trastuzumab for EBC is not associated with increased acute adverse events, including those of a cardiological nature (3, 4).Having said that, cardiotoxicity is becoming an increasingly important issue in modern medical practice as more and more patients are being treated with RT or chemotherapy and targeted therapies and are surviving longer. Moreover, the widely used definition of cardiotoxicity, originally created by oncologists decades ago and based on the development of heart failure symptoms and/or left ventricular ejection fraction reduction, has become obsolete. In fact, it refers to the detection of cardiac damage only after the onset of cardiac dysfunction and does not take into consideration the possibility of taking timely preventive measures. Finally, the survival rate of cancer patients has greatly increased over the past twenty years (5), making those who recover at higher risk for cardiovascular events.In this context, Cihan et al. (6) published in this issue evaluated the effect of RT, trastuzumab and hormone therapy sequencing on cardiac function in animal models. A single 12-Gy fraction to the rats caused increased fibrosis of the atrium, left ventricle and aorta after 6 months with respect to the control group. The trastuzumab-only treated arm also had higher fibrosis scores than the control group. Interestingly, this study highlighted a difference in the effect of the hormonal agents used, i.e. anastrozole and exemestane reduced the severity of the fibrosis, whereas letrozole and tamoxifen showed no impact on the myocardial damage induced after RT and trastuzumab administration.In Azria et al. (7) preclinical study of breast cancer cells transfected with an aromatase gene, letrozole showed a strong radiosensitising effect. However, the same authors did not observe a clinically meaningful effect in terms of the occurrence of acute or late adverse events w...

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Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors

Abstract: TIC is a frequent, albeit generally mild, adverse event in clinical practice. Further studies are warranted to better define the risk of and protective factors for TIC.

Cited by 99 publications

References 29 publications

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

The impact of radiotherapy, trastuzumab and hormonal therapy on cardiac fibrosis. More is worse?

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