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Personalized Assay May Aid in Determining Risk of Recurrence of Triple-Negative Breast Cancer

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Key Points

  • In a training set of 44 primary triple-negative breast tumors, the MHCII Immune Activation Score was significantly associated with longer disease-free survival.
  • In an independent validation cohort of 56 primary formalin-fixed paraffin-embedded triple-negative breast tumors, the immune activation score was significantly associated with longer disease-free survival.
  • An immune activation score threshold for identifying patients with very low risk of relapse in the training set provided 100% specificity in the validation cohort.

Sixty percent of patients with triple-negative breast cancer will survive more than 5 years without disease after standard treatment, but 4 out of 10 women will have a rapid recurrence of the disease. There are currently no clinical tests to assess an individual patient’s prognosis, so all patients receive aggressive chemotherapy. Katherine Varley, PhD, a researcher at the Huntsman Cancer Institute and Assistant Professor of Oncological Sciences at the University of Utah, and colleagues recently published findings in Cancer Research that may allow for more personalized assessment of risk of recurrence.

Previous research reported by Forero et al in Cancer Immunology found that patients with triple-negative breast cancer whose tumors naturally turned on an immune response were disease-free for much longer than those who did not. The objective of the new study was to find a way to translate this discovery into a clinical test to determine which patients have an inherently good prognosis and might safely be treated with less aggressive therapy.

Study Methods

The research team used tumor specimens were taken more than 5 years ago, so the researchers could determine how each patient fared in the long term. The next step was developing a way to test for biomarkers of the immune response. The biomarker test—a major histocompatibility complex class II (MHCII) Immune Activation Assay—was developed using formalin-fixed paraffin-embedded tissues. This is important because it means this test can be run on tumor biopsy specimens that are routinely collected for breast cancer diagnosis.

Assay Effectiveness

The assay measurements were concordant with RNA-seq, MHCII protein expression, and tumor-infiltrating lymphocyte counts. In a training set of 44 primary triple-negative breast tumors, the MHCII Immune Activation Score was significantly associated with longer disease-free survival (hazard ratio [HR] = 0.17, P = .015). In an independent validation cohort of 56 primary formalin-fixed paraffin-embedded triple-negative breast tumors, the immune activation score was significantly associated with longer disease-free survival (HR = 0.19; P = .011), independent of clinical stage. An immune activation score threshold for identifying patients with very low risk of relapse in the training set provided 100% specificity in the validation cohort.

The research team is currently applying the test to triple-negative breast cancer patient samples from clinical trials of chemotherapy and immunotherapy. Their next step is to validate that the test can be used to predict prognosis and choose the most effective and safest treatments. They are also investigating whether this test could be used for patients with HER2-positive breast cancer, lung cancer, ovarian cancer, and melanoma, because the immune response is similar in those diseases.

“We could very accurately predict which patients were going to have long-term disease-free survival and which patients were likely to have recurring disease. This is very exciting, because it could be the first clinical test to enable personalized prognosis for [patients with] triple-negative breast cancer,” said Dr. Varley.

Disclosure: This research was supported by the National Cancer, the National Institutes of Health National Center for Advancing Translational Sciences, Huntsman Cancer Foundation, and the Biospecimen Procurement and Translational Pathology and Oncogenomics Shared Resource Facilities of the University of Kentucky Markey Cancer Center. For full disclosures of the study authors, visit cancerres.aacrjournals.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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