Cardiac toxicity is the most significant adverse effect of trastuzumab (Trastuzumab s). Advanced age, prior heart disease, radiation therapy to the chest, and use of anthracyclines all increase the cardiotoxicity of trastuzumab.
What heart problems may trastuzumab cause?
- Screening for left ventricular insufficiency may also cause a decrease in left ventricular ejection fraction (LVEF) (suggesting a decrease in the heart’s pumping function) leading to related symptoms.
- Cardiac arrhythmias.
- Hypertension.
- Heart failure presenting as a symptom.
- Cardiomyopathy.
- Death from cardiac causes.
How likely is trastuzumab to cause cardiotoxicity?
Some studies have shown that trastuzumab is less likely to cause cardiotoxicity, and researchers have noted that most people treated with trastuzumab after chemotherapy do not experience cardiotoxicity, and most of those who do experience cardiotoxicity recover left ventricular function after stopping trastuzumab.
The rate of cardiotoxicity over 3.6 years was reported to be 4.4% in those on trastuzumab for 1 year and 0.6% in those not on the drug, but most adverse cardiac events are reversible.
Other studies reported that the rates of discontinuation of trastuzumab therapy due to cardiotoxicity in patients on trastuzumab for 2 years and 1 years were 9.4% and 5.2%, respectively, with or without trastuzumab and for how long, the rates of death due to cardiac causes, development of severe heart failure, and The incidence of significant reduction in LVEF was low, but in patients on trastuzumab for 2 years and 1 years, severe congestive heart failure ( 0.8%, 0.8% and 0, respectively), significant reduction in LVEF (  ;7.2%, 4.1% and 0.9%) occurred more frequently than in those who did not apply the drug. Among patients who developed cardiotoxicity on trastuzumab, there was 87.2% and 79.5% recovery at 7.2 months and 6.6 months, respectively.
As seen, all cardiac adverse events occurred during trastuzumab treatment, and fewer cardiac adverse events occurred after discontinuation of treatment.
How to prevent and treat cardiotoxicity with trastuzumab?
Before the first dose of trastuzumab, the physician will fully assess the patient’s cardiac function, including taking a detailed history, performing a physical examination, and performing an echocardiogram or even a cardiac angiogram. The decision to use trastuzumab and the timing of treatment initiation is made only after the physician has thoroughly assessed the risk of cardiotoxicity.
The LVEF is typically measured by cardiac ultrasound every 3 months during trastuzumab treatment and at the end of treatment.
- Physicians may ask to stop trastuzumab therapy if LVEF is reduced from pre-treatment to a certain level, or if LVEF is below normal and reduced relative to pre-treatment to a certain level.
- If symptomatic heart failure occurs during treatment, your doctor may give standard therapy with diuretics, cardiac glycosides, and/or angiotensin-converting enzyme inhibitors (ACEIs).
- For patients with symptomatic heart failure, doctors generally do not give trastuzumab unless the benefit outweighs the risk.
- Physicians generally do not recommend trastuzumab for patients who have had heart failure, have severe uncontrolled arrhythmias, have angina requiring medication, have some valve disease, have an electrocardiogram that shows a more severe myocardial infarction, or have poorly controlled hypertension.
In addition to this, serious infusion reactions and pulmonary toxicity have been reported during the use of trastuzumab.
When should I be evaluated for cardiotoxicity when receiving trastuzumab?
1 year is the standard time to receive trastuzumab for patients with human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. Most guidelines recommend that trastuzumab should be evaluated before starting trastuzumab therapy, monitored during the 3rd, 6th, and 9th months of therapy and at the 12th and 18th months after starting therapy, and of course, suspected cardiac adverse effects during therapy The patient should be examined at any time when an adverse cardiac reaction is suspected during treatment.
Physicians generally recommend stopping trastuzumab therapy for at least 4 weeks and testing 1 LVEF every 4 weeks if any of the following occur.
- Absolute decrease in LVEF from pre-treatment values ≥16%.
- LVEF below the normal range for this provider and LVEF decreased by ≥10% in absolute terms from pre-treatment values.
- Trastuzumab may be resumed if LVEF returns to the normal range or LVEF decreases by ≤15% in absolute terms from pretreatment values within 4 to 8 weeks.
- A sustained decline in LVEF (>8 weeks) or more than 3 discontinuations of trastuzumab therapy due to cardiomyopathy, discontinue trastuzumab permanently.
Trastuzumab specifically acts on HER2 to exert anti-breast cancer effects, however, cardiotoxicity also often leads to concerns in patients applying trastuzumab. Doctors will weigh the pros and cons to make appropriate treatment recommendations. (Contributed by Yuqing Yang, Xijing Hospital, Air Force Military Medical University)