HER2 Phosphorylation and Dimerization with EGFR Predict Neoadjuvant HER2+ pCR for Personalized (Escalation or De-Escalation) Breast Cancer Therapy
Abstract
In about 1 of every 5 breast cancers, the cancer cells make an excess of a surface protein called HER2. When breast cancer is diagnosed by a biopsy, the pathologist scores whether the cancer cells have high levels of HER2. If so, the cancer is then designated to be HER2-positive. HER2-positive breast cancers tend to be more aggressive than other types of breast cancer because when the HER2 protein is active and “firing,” it stimulates the cancer to grow and spread. Fortunately several treatments exist that specifically target HER2-positive cancers. These treatments are very effective. They are so effective that approximately 50% of the patient’s tumors are completely absent: The tissue where the tumor was located does not containing any living tumor cells when examined by the pathologist. This level of effectiveness following a cancer treatment is called completed pathologic response or pCR. It is known that patients whose tumors are classified as pCR will have a much better long-term survival compared to patients in which some of the tumor remains after treatment. We have developed a test to predict the likelihood that an individual patient’s HER2-positive tumor will respond so well to HER2 therapies that the response will be classified as a highly favorable pCR. Our new test measures whether the HER2 protein is active or “firing.” The test is performed on the diagnostic biopsy at the time the patient is receiving the diagnosis of a HER2-positive tumor. The test works on different classes of HER2 therapies. No additional biopsy or x-ray imaging is required. We believe the test can have great benefit for individualizing therapies. Two classes of patients can immediately benefit from this test. The first class are patients who are predicted to be good responders but may be subject to cardiac toxicity or nerve toxicity depending on the choice and length of the therapies. For these patients, if our test predicts a good response, then these patients can receive less toxic or shorter duration treatments (that are already clinically approved). For patients predicted to have a low chance of having a successful tumor treatment response (about half), they can be started on additional HER2 treatment choices (that are already approved) to increase their chances of undergoing a favorable tumor response. We have already shown that our test can generate a highly accurate prediction of complete pathologic response by studying patients in the national breast cancer ISPY clinical trial. Our test was evaluated on blinded data. We did not know the outcome ahead of time. Under the proposed project, we will continue to evaluate our test using previously collected patient cases from the ISPY trial, while we independently evaluate our test in a separate group of patients that have already been treated at the Rutgers Cancer Center. We will not know the outcome (whether the patient’s tumors responded to HER2 therapy) ahead of time. The Rutgers study group mimics the real-world situation where treating physicians decide the class of HER2 therapy they recommend to the patient. Our academic lab is certified to conduct patient testing. The outcome of the study, if successful, will be a new test for predicting HER2 treatment response that can be widely adopted for use in clinical trials. The new test, conducted on the original biopsy, can become a routine part of individualized therapy planning for any patient diagnosed with a HER2-positive breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110044
Entities
People
- Lance A. Liotta
Organizations
- George Mason University
- United States Army