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2019 ASCO-SITC: Genetic Characterization of BRCA-Mutant Prostate Cancer

By: Lauren Harrison, MS
Posted: Monday, March 4, 2019

BRCA2-mutant prostate cancers may be sensitive to immune checkpoint blockade due to a change in immunogenicity, which is not characteristic of similar microsatellite-stable tumors. Anshuman Panda, PhD, of the Rutgers Cancer Institute of New Jersey, and colleagues presented their data during a poster session at the 2019 American Society of Clinical Oncology (ASCO)–Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Symposium in San Francisco (Abstract 59).

“The effect of BRCA1/2 mutation on immunogenicity may be very tissue- and/or cell-of-origin–specific, with different cancer types having different levels of immune activation. The association between endogenous retrovirus expression and BRCA2-mutation in prostate cancer requires further investigation,” Dr. Panda and colleagues reported.

The investigators treated a patient with BRCA2-mutant microsatellite-stable prostate cancer with pembrolizumab after the patient had failed to respond to previous therapy. This patient had a rapid and ongoing response to pembrolizumab, so other BRCA-mutant tumors in The Cancer Genome Atlas data set were identified and screened for expression levels of different genes. These tumors showed significant expression of CD8 T-cell marker and the immune checkpoint genes PD-1 and CTLA-4. In addition, expression of endogenous retroviruses was increased in these tumor types.

Upregulation of this unique set of genes was also noted in BRCA1-mutant estrogen receptor–positive breast cancer—but not in BRCA-mutant triple-negative breast or ovarian cancer. The team was able to establish an association between endogenous retrovirus expression in BRCA mutants and upregulation of T-cell infiltration and checkpoint pathway genes.

Disclosure: The study authors’ disclosure information may be found at coi.asco.org.



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