2023-05-22 13:45:43
At Baylor College of Medicine, a team of researchers, led by Dr. Rachel Schiff and Dr. Mothaffar F. Rimawi, have taken a step closer to achieving personalized treatment for breast cancer. These researchers have developed a method to predict with high accuracy which patients with HER2 breast cancer would be candidates for anti-HER2 treatment without the need for chemotherapy.
New perspectives in the personalized treatment of breast cancer
HER2 type breast cancers account for regarding one fifth of all breast cancer cases. They express high levels of HER2 protein and are physiologically dependent on the abundance of this protein to grow rapidly and metastasize. Traditionally, this type of cancer was treated with chemotherapy alone, but the results for patients were disappointing. This changed in the late 1990s with the introduction of anti-HER2 therapies, drugs that block the growth effects of HER2, thereby transforming the treatment of this disease.
The Baylor College of Medicine team has developed and validated in clinical trials a multiparametric molecular test to predict with a high level of confidence which patients would be candidates for anti-HER2 treatment without chemotherapy. This molecular test also makes it possible to precisely identify patients whose tumors may require chemotherapy or other targeted therapies.
A molecular test for targeted treatments
The molecular test developed by the researchers consists of three components. The first measures the amount of HER2 genes and proteins in cancer cells and checks whether the expression is homogeneous throughout the tumor. The second analyzes whether the cancer expresses a set of genes reflecting the dependence of cancer growth on HER2. Finally, the third component examines the PIK3CA gene. Mutations in this gene bypass HER2-mediated pathways, providing alternative molecular pathways for cancer cell growth when the HER2 protein is blocked.
The test was performed on tumor samples from two previous clinical trials. To be a candidate for anti-HER2 therapy without chemotherapy, a tumor must have all the characteristics mentioned above.
Towards a more precise therapeutic approach
In addition to identifying patients who might benefit from HER2-targeted therapy alone, the test can also accurately identify patients whose tumors are not HER2-dependent and therefore might not be good candidates. for treatment de-escalation.
“Traditionally, in an effort to remove the tumor, we give patients more aggressive treatments, but these also increase toxicity and affect patients’ quality of life,” said Dr. Jamunarani Veeraraghavan, first author of the study. “But when we provide personalized treatment, we give patients what they need to treat the tumour, not more, thus minimizing the impact on their quality of life. This is an essential aspect of precision medicine that we do not don’t want to miss.”
Promising results for the future
“Studying the biology of the tumor tells us what would be needed to clear the tumor. Our results strongly support the idea that safe de-escalation of treatment is possible,” Dr. Rimawi said. The Baylor researchers now plan to evaluate their molecular test in a prospective clinical trial to confirm its clinical utility. If this test is validated, it might serve as a molecular triage tool to safely and appropriately select patients with HER2 breast cancer for treatment de-escalation.
This discovery is the product of many years of research and might represent a significant advance in the treatment of HER2 breast cancer. By identifying patients who may benefit from more targeted treatment, researchers hope to improve not only therapy outcomes, but also patients’ quality of life.
Clin Cancer Res CCR-22-3753.
https://doi.org/10.1158/1078-0432.CCR-22-3753
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