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Difficulty: MediumMonitoring and Treatment Evaluation

A 54-year-old woman comes to the oncology clinic for a routine follow-up visit. Six months ago, she underwent a lumpectomy and adjuvant radiation therapy for early-stage right breast cancer. Surgical pathology revealed a tumor that was positive for human epidermal growth factor receptor 2 (HER2) and negative for estrogen and progesterone receptors. She recently completed a course of paclitaxel and is currently receiving maintenance therapy with trastuzumab. She has a history of well-controlled essential hypertension and type 2 diabetes mellitus. Her current medications include lisinopril, metformin, and trastuzumab. She reports feeling well, has resumed her normal daily activities, and exercises for 30 minutes daily without difficulty. She denies chest pain, shortness of breath, orthopnea, or lower extremity edema. Her blood pressure is 124/76 mm Hg, and pulse is 72/min. Physical examination reveals clear lungs, a regular heart rhythm with no murmurs, and no jugular venous distention or peripheral edema. Which of the following is the most appropriate next step in the management of this patient?

  1. EchocardiographyAnswer
  2. B
    Positron emission tomography scan
  3. C
    Pulmonary function testing
  4. D
    Measurement of serum CA 15-3
  5. E
    Discontinuation of lisinopril

Answer

Echocardiography
The correct step is to perform echocardiography. Trastuzumab is a monoclonal antibody that targets the HER2 receptor and is a cornerstone in the management of HER2-positive breast cancer. A well-recognized and significant adverse effect of trastuzumab is cardiotoxicity. Unlike anthracycline-induced cardiotoxicity (e.g., doxorubicin), which causes cumulative, dose-dependent, and often irreversible myocardial damage (Type I cardiotoxicity), trastuzumab causes Type II cardiotoxicity. This is typically not dose-dependent, does not cause ultrastructural changes to the myocardium, and is often reversible upon cessation of the drug. Because the decline in left ventricular ejection fraction (LVEF) is frequently asymptomatic, patients require routine, scheduled monitoring. Clinical guidelines recommend assessing LVEF with echocardiography (or a MUGA scan) at baseline prior to initiation, and subsequently every 3 months during active therapy.

Step-by-Step Solution

1
Identify the patient's active high-risk pharmacotherapy.
The patient is currently receiving maintenance therapy with trastuzumab for HER2-positive breast cancer.
Specific chemotherapeutic and targeted biologic agents have unique, significant toxicity profiles that mandate routine clinical monitoring.
2
Recall the major toxicity associated with trastuzumab.
Trastuzumab is known to cause cardiotoxicity, most commonly manifesting as an asymptomatic decrease in left ventricular ejection fraction (LVEF).
Understanding the adverse effect profile dictates the required surveillance testing.
3
Determine the appropriate monitoring protocol for this toxicity.
Echocardiography (or a MUGA scan) should be ordered to assess LVEF at baseline and typically every 3 months during treatment.
Because the decline in cardiac function is frequently asymptomatic initially, regular objective imaging of cardiac contractility is the standard of care.

Key Concept

Patients receiving trastuzumab require routine monitoring of left ventricular ejection fraction (LVEF) with echocardiography at baseline and every 3 months due to the significant risk of cardiotoxicity.
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Topics

Monitoring and Treatment Evaluation

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