A 61-year-old woman comes to the physician due to mild exertional dyspnea. She has difficulty going up the stairs and feels very tired by the end of the day. She has no chest pain, orthopnea, lower extremity swelling, or syncope. The patient is being treated for locally advanced HER2-positive breast cancer. She underwent left-sided mastectomy and received adjuvant chemotherapy with docetaxel and carboplatin in addition to trastuzumab 6 months ago. Preoperative evaluation showed normal cardiac function. Currently, the patient receives periodic trastuzumab infusions. Echocardiogram shows a left ventricular ejection fraction of 30%. The patient wonders if her symptoms are related to cancer therapy and wants to know her long-term prognosis. What is the best response to this patient's concerns?

Question

A 61-year-old woman comes to the physician due to mild exertional dyspnea.  She has difficulty going up the stairs and feels very tired by the end of the day.  She has no chest pain, orthopnea, lower extremity swelling, or syncope.  The patient is being treated for locally advanced HER2-positive breast cancer.  She underwent left-sided mastectomy and received adjuvant chemotherapy with docetaxel and carboplatin in addition to trastuzumab 6 months ago.  Preoperative evaluation showed normal cardiac function.  Currently, the patient receives periodic trastuzumab infusions.  Echocardiogram shows a left ventricular ejection fraction of 30%.  The patient wonders if her symptoms are related to cancer therapy and wants to know her long-term prognosis.  What is the best response to this patient's concerns?

Quizplus · Accepted Answer

Explanation: This patient has developed trastuzumab-associated cardiotoxicity. Trastuzumab is a monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2). It is used in addition to adjuvant chemotherapy for the treatment of patients with HER2-positive tumors. Trastuzumab may cause a decline in left ventricular ejection fraction (LVEF), which is usually asymptomatic but may occasionally lead to overt clinical heart failure. The incidence of cardiotoxicity is approximately 5% with trastuzumab monotherapy, but it is 25% with trastuzumab combined with anthracycline (eg, doxorubicin) and cyclophosphamide. In most patients, trastuzumab-associated cardiotoxicity is reversible; there is complete recovery of cardiac function after treatment discontinuation. In contrast, chronic anthracycline-associated cardiotoxicity may not be reversible after treatment discontinuation due to myocyte necrosis, destruction, and replacement by fibrous tissue. (Choice A) Trastuzumab-related cardiotoxicity is due to loss of myocardial contractility (myocardial hibernation) leading to a decrease in LVEF. It is not associated with accelerated atherosclerosis. (Choice B) Cardiotoxicity with anthracyclines is strongly related to cumulative doses but trastuzumab-associated cardiotoxicity is not dose-related. (Choice D) Trastuzumab should be withheld for 4 weeks if LVEF decreases by >16% from baseline, or by 10%-15% from baseline to below the lower limits of normal. It should be completely discontinued if patients develop symptomatic heart failure. (Choice E) Trastuzumab-related cardiotoxicity responds well to standard therapy for heart failure, including beta-blockers and angiotensin converting enzyme (ACE) inhibitors. Educational objective: Trastuzumab-related cardiotoxicity usually presents with an asymptomatic decline in left ventricular ejection fraction, but may occasionally lead to overt heart failure. It is unrelated to cumulative dosage and is often reversible in most patients after discontinuation of trastuzumab therapy. References: Trastuzumab-associated cardiotoxicity (http://www.ncbi.nlm.nih.gov/pubmed/12237930) Cardiotoxicity associated with trastuzumab treatment of HER2+ breast cancer (http://www.ncbi.nlm.nih.gov/pubmed/19669637)

A 61-Year-Old Woman Comes to the Physician Due to Mild