A 52-year-old woman with a history of locally advanced breast cancer comes to the office for follow-up. The patient is undergoing trastuzumab-based chemotherapy but has not received radiation therapy. She has no symptoms except mild fatigue. Blood pressure is 120/72 mm Hg and pulse is 85/min and regular. The patient is afebrile. Transthoracic echocardiography reveals a left ventricular ejection fraction of 40% with no evidence of valvular disease. Cardiac assessment prior to chemotherapy initiation was normal. Which of the following pathologic findings is most likely to be present in this patient's heart?

Question

A 52-year-old woman with a history of locally advanced breast cancer comes to the office for follow-up.  The patient is undergoing trastuzumab-based chemotherapy but has not received radiation therapy.  She has no symptoms except mild fatigue.  Blood pressure is 120/72 mm Hg and pulse is 85/min and regular.  The patient is afebrile.  Transthoracic echocardiography reveals a left ventricular ejection fraction of 40% with no evidence of valvular disease.  Cardiac assessment prior to chemotherapy initiation was normal.  Which of the following pathologic findings is most likely to be present in this patient's heart?

Quizplus · Accepted Answer

Trastuzumab is a monoclonal antibody used in the treatment of breast cancer caused by tumor cells that overexpress human epidermal growth factor receptor-2 (HER2). By binding to HER2, trastuzumab blocks downstream signaling that promotes cellular proliferation and thereby encourages malignant cell apoptosis. The major adverse effect of trastuzumab is a risk of cardiotoxicity, likely because HER2 signaling plays a role in minimizing oxidative stress on cardiomyocytes and preserving cardiomyocyte function. Cardiotoxicity typically manifests as a decrease in myocardial contractility (myocardial stunning) without cardiomyocyte destruction or myocardial fibrosis. Patients usually experience an asymptomatic decline in left ventricular ejection fraction; however, overt heart failure can also occur. Unlike the cardiotoxicity that occurs with anthracyclines (eg, doxorubicin), trastuzumab-induced cardiotoxicity is not related to the cumulative chemotherapy dose and is often reversible with discontinuation of therapy. (Choice A) Abnormal protein accumulation in the cardiac extracellular space is seen in patients with amyloidosis, namely with the light-chain (AL) and transthyretin (ATTR) subtypes. The disease typically manifests initially as restrictive cardiomyopathy with impaired diastolic function and preserved ejection fraction. (Choice B) Focal ischemic cardiomyocyte necrosis leading to left ventricular systolic dysfunction is seen in patients with a prior myocardial infarction due to coronary heart disease. (Choice C) Breast cancer is one of the most common malignancies to metastasize to the heart, typically causing pericardial effusion that may gradually progress to cardiac tamponade. However, tamponade predominantly affects diastolic filling of the right-sided heart chambers and does not decrease left ventricular ejection fraction. (Choice D) Anthracycline-induced cardiotoxicity occurs due to oxidative damage of cellular membranes, leading to cardiomyocyte necrosis and death with eventual myocardial fibrosis. Educational objective: Trastuzumab is a monoclonal antibody that blocks human epidermal growth factor receptor-2 (HER2) to disrupt malignant cell signaling and encourage apoptosis. Because HER2 helps preserve cardiomyocyte function, trastuzumab can cause cardiotoxicity that manifests as a decrease in myocardial contractility without cardiomyocyte destruction or myocardial fibrosis. __________ References: Twenty years of anti-HER2 therapy-associated cardiotoxicity. (http://www.ncbi.nlm.nih.gov/pubmed/27843627) Cardiotoxicity associated with trastuzumab treatment of HER2+ breast cancer. (http://www.ncbi.nlm.nih.gov/pubmed/19669637)

A 52-Year-Old Woman with a History of Locally Advanced Breast