By: David Vaught, Ph.D.
Research Grants Manager
All breast cancer research has one ultimate goal: to help patients live longer and with better quality of life. Research that leads to prevention, early detection, new treatment strategies, and improved access to and utilization of healthcare services moves us towards this goal. Recently, work by one of our Komen-funded investigators made its way from the lab to a clinical trial, revealing new information about the treatment of breast cancer.
Breast cancers are diverse and complex, making them difficult to treat. This is why a single treatment strategy will not work on all. Therefore, classifying and understanding the individual characteristics of a breast cancer such as tumor grade, stage and molecular subtype helps clinicians find the most effective treatments.
Aleix Prat, M.D., Ph.D. is currently Head of the Medical Oncology Department and Team Leader at the Institute for Biomedical Research August Pi i Sunyer (IDIBAPS) in Spain. Prior to this, Dr. Prat trained in the laboratory of Komen Scholar Dr. Charles Perou, where he studied HER2-positive breast cancer, a molecular subtype of breast cancer that accounts for 15-20 percent of all cases. However, this subtype of breast cancer is not a uniform disease - patients with HER2-positive breast cancer can respond differently to the same treatment. During his training, Dr. Prat and a team of scientists showed that the HER2-positive breast cancer subtype can be classified into four different subtypes within itself. This new information could be used to better inform patient prognosis and treatment versus knowing the HER2 subtype status alone.
Dr. Aleix Prat (center) and his lab at the Institute for Biomedical Research August Pi i Sunyer in Spain
One of the subtypes that they identified is called HER2-enriched (HER2-E) – “enriched” because it has high levels of the protein called HER2 as well as high levels of the genes that “turn on” HER2, which means these tumors are more aggressive. These findings led Dr. Prat to carry out a clinical trial known as PAMELA (PAM50 HER2-enriched Phenotype as a Predictor of Response to Dual HER2 Blockade in HER2-positive Early Breast Cancer).
The current standard of care for patients with HER2-positive breast cancer is treatment with chemotherapy + a drug that blocks HER2 activity (trastuzumab, lapatinib or pertuzumab). The goal of the PAMELA trial was to determine if HER2-E could be a biomarker (a biological signal) for patients with HER2-positive breast cancer who have a good chance of responding well to trastuzumab + lapatinib treatment without the use of chemotherapy. If successful, this study could reveal a subset of patients that could be spared the harsh side effects of chemotherapy while receiving treatment that improves survival.
After analyzing 151 patient tumor samples collected from this clinical trial (with support from Komen), Dr. Prat’s study confirmed that the HER2-E biomarker can be measured early during treatment and can identify patients more likely to benefit from trastuzumab + lapatinib treatment without chemotherapy. The novel results of this study, published in a leading journal - Lancet Oncology - not only show remarkable treatment response and promise for patients with the HER2-E subtype, but also identify those patients with HER2-positive breast cancer that can avoid chemotherapy.
“I truly believe our results are very important and especially relevant for this group [HER2-E] of patients who have newly diagnosed, early-stage, HER2-positive tumors where the benefit of anti-HER2 therapy before or after surgery is very high. The results of this study have opened the door on a potential new treatment strategy, allowing us to determine if some patients can be cured with drugs that block HER2 but without the need for chemotherapy,” says Dr. Prat.
Although this work is an important first step, Dr. Prat and his team plan to validate their findings in a different set of patient samples to make sure their observations are consistent in more than one clinical trial. Overall, these results should help physicians make more informed decisions about the clinical care of patients with HER2-positive breast cancer, which could improve overall survival and patient quality of life.
You can learn more about Komen’s investment in HER2-positive Breast Cancer and read a previously published Komen Blog on Dr. Prat’s Komen-funded research.
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