UH3CA262221

Validation of the MHC II Immune Activation Assay in Breast Cancer - Project Summary/Abstract

The development of clinical biomarker tests to assess risk of recurrence in ER+ breast cancer patients has led to dramatic improvements in patient care and outcomes, including the de-escalation of chemotherapy and reduction of adverse side-effects for women with good prognosis.

There are currently no clinical biomarker tests available to assess risk of recurrence in triple negative breast cancer (TNBC) patients or HER2+ breast cancer patients. These patients are all treated with aggressive chemotherapy and often suffer from long-term adverse side-effects because oncologists have no way of knowing which patients inherently have a good prognosis.

We recently discovered that expression of the MHC class II antigen presentation pathway (MHCII) and the presence of tumor infiltrating leukocytes (TILs) was associated with long-term disease-free survival (DFS) in TNBC and HER2+ breast cancer patients. We developed a multigene expression assay compatible with formalin fixed paraffin embedded breast tumor specimens that can accurately quantify MHCII expression and TILs to generate an immune activation score for each patient. We confirmed that the immune activation score could identify patients who have a very low risk of recurrence in an independent institutional cohort.

Interestingly, patients with high MHCII and TIL expression have long-term disease-free survival regardless of whether they received chemotherapy. Additionally, mouse studies show that MHCII expression in tumors increases TILs and protects from recurrence in the absence of chemotherapy, and other groups have recently reported that TNBC patients with high TILs have improved DFS even without receiving chemotherapy. These data suggest that the MHCII immune activation assay can identify TNBC and HER2+ patients who have a very low risk of recurrence.

The primary objective of this UH3 proposal is to validate that the MHCII immune activation assay can be used to identify TNBC and HER2+ breast cancer patients who have a very low risk of recurrence by analyzing clinical trials specimens in a CLIA-certified laboratory. Specific Aim 1 analyzes tumors from a large trial of adjuvant chemotherapy in TNBC and HER2+ patients, and Specific Aim 2 analyzes biopsies from TNBC patients who received neoadjuvant chemotherapy (NAC). This ensures the assay is prognostic using different specimen types and treatment timing.

A secondary objective is to determine if the assay can identify good prognosis patients who do equally well regardless of whether their chemotherapy regimens include paclitaxel. Exploratory objectives include determining if high immune activation scores are predictive of pathological complete response to NAC, and determining if MHCII immune activation scores change after NAC and are associated with DFS.

The successful completion of this study could produce the first biomarker assay for identifying TNBC and HER2+ breast cancer patients who have a low risk of recurrence. It would also enable future clinical trials to utilize the assay for selective enrollment of good prognosis patients to evaluate less toxic treatment regimens.

University Of Utah

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Utah United States

State-Wide

Assay Validation of High Quality Markers for Clinical Studies in Cancer (UH3 Clinical Trials Not Allowed) (PAR-20-314)

Amendment Since initial award the total obligations have increased 193% from $351,220 to $1,029,625.