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Case history

image A 67-year-old woman presented with a 1.9 cm nodule in her left breast. Biopsy revealed a grade 3 infiltrating ductal cancer that was oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative and human epidermal growth factor receptor 2 (HER2)-positive. A lumpectomy with sentinel node dissection was performed. Two out of four nodes were found to be positive for metastasis. She underwent complete axillary node clearance. All other nodes were clear of cancer.

Her medical history included hypertension controlled with ramipril and diet-controlled type 2 diabetes. She was an ex-smoker with a 20 pack-year smoking history. Her ECG showed sinus rhythm and was within normal limits. Her routine bloods tests were all normal.

She was keen to try any treatment option to reduce her risk of recurrence. A plan was made to start anthracycline-based chemotherapy followed by docetaxel and then trastuzumab for 1 year.

What are the risk factors for cardiac toxicity with anthracycline and trastuzumab?

Are newer HER2-targeted agents less cardiotoxic?

Are there any other cytotoxic drugs with potential to cause cardiac toxicity? What common cardiotoxicities are they associated with?

What are the common cardiac side effects of newer targeted treatments in oncology practice?

How should this patient be managed and followed up?

What are the risk factors for cardiac toxicity with anthracycline and trastuzumab?

Anthracycline

Anthracyclines are a class of antibiotics and are among the most effective anticancer drugs, but their use is limited by short- and long-term cardiotoxic effects. Commonly used anthracyclines include doxorubicin, mitoxantrone, epirubicin, idarubicin and daunorubicin.

The cumulative dose appears to be the strongest predictor of short- and long-term cardiac side effects. Although there is a wide range of individual susceptibility, doses above 300 mg/m2 of doxorubicin or 900 mg/m2 of epirubicin are associated with a higher incidence of heart failure events.13 There is also evidence that concurrent administration of other agents that affect heart function (e.g. trastuzumab) increases toxicity4 and that liposomal formulations are less toxic.5 Patient risk factors include age: those >65 years have a higher risk of events at a given dose.6 There is equivocal evidence for other risk factors including chest radiotherapy and pre-existing cardiovascular disease (including coronary artery disease, hypertension, peripheral vascular disease and diabetes).7,8

The mechanism of cardiac toxicity due to anthracyclines is incompletely understood, but is generally attributed to the production of toxic oxygen free radicals and an increase in oxidative stress, which can lead to cardiac myocyte apoptosis.7

Dexrazoxane, a derivative of EDTA, was developed to provide cardioprotection against anthracycline-induced cardiotoxicity by reducing superoxide free radicals. Its use has been limited by concern regarding reduced anti-tumour effect and risk of second malignancy,9,10 but more recent analyses have called this concern into question11 and its use is being reconsidered in guidelines.

Trastuzumab

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