A new molecular analysis tool accurately detected the level of an important target for immunotherapy in early stage breast cancers. The diagnostic test, using RNAScope, measures the amount of programmed death ligand 1 (PD-L1) mRNA in routine formalin-fixed cancer tissues and is devoid of many of the technical issues that plague antibody-based detection methods that have yielded conflicting results in the past. PD-L1 is the target of several novel immune stimulatory therapies in clinical trials.

PD-L1 is a protein that plays an important role in suppressing immune response, and in cancer, it may allow tumors to evade immune attack. The study demonstrated that about 60% of early stage breast cancers have PD-L1 expression, and a subset of these cancers also have large numbers of tumor infiltrating lymphocytes. High levels of lymphocytes and PD-L1 predicted for better survival, suggesting a beneficial role for the immune system in at least partially controlling these cancers.

“This is exciting  because these findings provide the rationale to test PD-L1 targeted therapies in breast cancer with the hope of further improving cure rates in early stage breast cancer,” said co-author Lajos Pusztai, MD, DPhil, professor of Medical Oncology and chief of Breast Medical Oncology at Smilow Cancer Hospital at Yale Cancer Center in New Haven, Connecticut. The study was published in the Journal of Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-13-2702).

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“Patients with many tumor infiltrating lymphocytes and high PD-L1 expression may be the ideal candidates for these therapies,” said Pusztai. He added that the in situ mRNA detection method used in the study eliminates many of the technical problems that older immunohistochemistry assays had.

The study concluded that their observations supported research to evaluate therapies targeting programmed death receptor 1 (PD-1) and PD-L1 in breast cancer. These types of therapies are emerging as promising in metastatic renal cancer, lung carcinomas, and melanomas, where they have led to lasting responses.