Investigating the Long-term Cardiac Sequelae of Trastuzumab Therapy

  • participants needed
  • sponsor
    University of Glasgow
Updated on 30 January 2023
her2/neu-positive breast cancer


The introduction of trastuzumab for the treatment of patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer has had a major impact upon cancer outcomes. However, cardiac toxicity remains a substantial concern. Conventionally, this toxicity has been considered as a transient and reversible phenomenon occurring in the immediate peri-treatment period in around 20% of patients. Current guidelines recommend monitoring heart function during treatment and at completion. Recent registry data suggest that trastuzumab-related cardiotoxicity may also manifest in the longer-term. The nature and longer-term prevalence of left ventricular dysfunction with HER2 positive breast cancer treated with trastuzumab is unclear. The aim of this project is to define the prevalence of left ventricular dysfunction late after completion of trastuzumab therapy.


In 2014, there were 45,535 cases of breast cancer diagnosed in England and Wales(1). Predicted 10-year survival in 2015, from data by the National Statistics office was estimated at 81%(2). Breast cancer is the most common malignancy in Scotland and the second most common cause of death(3). Around 1 in 4 of these cancers overexpress human epidermal growth factor receptor 2 (HER2). For these patients, trastuzumab is a recommended and highly effective component of a chemotherapy regime that usually includes an anthracycline(4).

Up to a quarter of patients treated with trastuzumab will develop cardiac dysfunction(5-7), conventionally defined as an asymptomatic >10% fall in left ventricular ejection fraction (LVEF) to an absolute LVEF <50%, or symptomatic heart failure(8). The risk is greater in patients who have received prior anthracyclines(9). Trastuzumab-related cardiotoxicity has, typically been considered to be a reversible phenomenon which recovers with interruption or cessation of treatment(10-14). The long-term benefit of cardioprotective treatment with angiotensin converting enzyme inhibitors or beta blockers when cardiotoxicity is detected is unclear(8) and these agents are often either not continued or not be prescribed at all.

The incidence of cardiac dysfunction or heart failure in the longer-term is not well-defined (12,14-20) . Clinical trials, which have excluded patients with baseline cardiovascular comorbidity, report no excess of cardiovascular events after the first two years(21-23) but observational studies report a much higher incidence of up to 23.8%(9,24). A landmark analysis of patients with a history of breast cancer (median follow-up 9 years) reported that patients treated with anthracycline chemotherapy and trastuzumab were three-fold more likely to develop heart failure than those treated with anthracycline alone. Importantly, these data were derived from a population censored at one year and reflect 'late' manifestations of cardiotoxicity rather than ongoing symptoms from an early diagnosis(25). This important study reported the incidence of symptomatic heart failure and not LV dysfunction which would be expected to be substantially more prevalent(26). Furthermore, the long-term implications of an apparently transient drop in LVEF during treatment are unclear.

Cardiovascular magnetic resonance (CMR) is the gold standard for the assessment of LV function(27). Previous work has demonstrated that CMR may be better able to identify small changes in LVEF related to chemotherapeutic agents(18,28,29). CMR has superior accuracy and precision when compared with echocardiography and allows myocardial tissue characterisation(30,31). My proposed CMR protocol will generate important insights into the long-term cardiac effects of trastuzumab and further novelty will be provided by the incorporation of tissue mapping methods(32) and LV strain assessment(33,34). Via collaboration with mathematicians I will also derive computational models.

Condition Breast Cancer, her2/neu-positive breast cancer, cancer, breast, Cardiotoxicity, Breast Cancer Diagnosis, her2-positive breast cancer, HER2 Positive Breast Cancer, breast carcinoma, Cardiac Toxicity
Clinical Study IdentifierNCT05019365
SponsorUniversity of Glasgow
Last Modified on30 January 2023

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note