Lead Investigator: Youssef Zeidan, American University of Beirut Medical Center
Title of Proposal Research: Evaluation of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Treated with Radiation Therapy and Trastuzumab
Vivli Data Request: 6068
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Background: Patients with breast cancer are usually treated depending on the types of receptors involved in the steps leading to the development of the cancer. For patients with HER-2 positive breast cancer (HER-2 is the Human Epidermal growth factor, a human protein that can affect the growth of breast cancer cells), the general adjuvant treatment plan includes trastuzumab – a monoclonal antibody that binds and counteracts HER-2 – with or without radiation therapy (monoclonal antibodies are proteins derived from a single cell line and bind to a single recognition site). This treatment plan has proven beneficial, leading to lower rates of locoregional recurrence (which is the reoccurrence of a tumor on a side previously affected by cancer), and an improved overall survival.
However, this treatment comes with a side effect profile that includes cardiotoxicity mainly in the form of declining left ventricular ejection fraction (LVEF). Left ventricular ejection fraction is a measure of the heart’s function; it measures the ability of the heart to pump blood. In addition, radiation therapy for breast cancer has also shown some cardiotoxic side effects.
The question remains as to whether the combination of trastuzumab in addition to radiotherapy for patients with HER-2 positive breast cancer leads to a compounded cardiotoxicity. This question has been answered by a few studies, however, the sample size was mostly relatively small.
To date, there are no large studies evaluating the cardiotoxicity of the concurrent use of radiotherapy and trastuzumab in patients with HER-2 positive breast cancer. We are in need of more studies with a larger sample size and longer follow-up. Therefore, the analysis of clinical data from the HERA trial – which includes more than 5,000 patients that were followed up for more than 10 years of follow-up – would be crucial to answer this question.
Necessity: Although previous studies have shown that there is no increase in cardiotoxicity with the addition of chest wall radiotherapy to adjuvant (post-cancer treatment) trastuzumab in the treatment of patients with HER-2 positive breast cancer, to date, there are no large scale studies with high statistical power and long follow-up to measure the cardiotoxicity profile with high efficacy. Therefore, this study would be able to help fine tune treatment modalities.
Effect: Since there are -to date- no large-scale studies that show the effect of concomitant radiotherapy and trastuzumab in treating patients with HER-2 positive breast cancer, the effect of this study is expected to impact all patients with HER-2 positive breast cancer being treated with radiation therapy and trastuzumab. Breast cancer is the most common diagnosed cancer among US females with a prevalence of around 70 per 100,000 in 2019. In addition, incidence of breast cancer is increasing (0.3% annually). It is estimated that 15-25% of patients with breast cancer are HER-2 positive, and this is associated with a more aggressive tumor behavior. Therefore, this study will have a large impact on patients with HER-2 positive breast cancer.
Requested Studies:
A Randomized Three-Arm, Multicenter Comparison of 1 Year and 2 Years of Herceptin Versus No Herceptin in Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy
Sponsor: Roche
Study ID: NCT00045032
Sponsor ID: BO16348
Update: This data request was withdrawn on 28-Apr-2022 by the researcher.