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Prostate Cancer Prognosis, Treatment Response Informed by Breast Cancer Expression Signature

NEW YORK (GenomeWeb) – A gene expression-based classification signature originally developed for distinguishing luminal and basal breast cancer cases is showing promise classifying prostate cancer cases in ways that help predict response to post-operative androgen deprivation therapy.

Researchers from the US and Canada applied a gene expression-based classifier called PAM50 — commercially developed by NanoString Technologies as the Prosigna test — to nearly 3,800 retrospectively or prospectively collected prostate cancer samples. With the assay, they successfully classified prostate cancers as luminal A, luminal B, and basal subtypes with distinct survival patterns and androgen deprivation therapy response rates. The study appeared online this week in JAMA Oncology.

"The clinical validation of the established breast cancer PAM50 signature for men with prostate cancer will help physicians to predict which patients are most likely to benefit from postoperative hormone therapy, allowing for personalized patient selection, potentially improving treatment outcomes and sparing many patients from unnecessary toxicity," senior author Felix Feng, a radiation oncology and urology researcher at UCSF, said in a statement.

Though prostate cancer prognostic signatures have been extensively explored, it remains challenging to reliably predict which prostate cancer cases will respond to a given treatment approach, he and his colleagues explained.

For their analyses, the investigators brought together Affymetrix array-based expression data for formalin-fixed paraffin-embedded samples from individuals who had undergone radical prostatectomy surgery. These samples included 1,567 prostate cancers assessed retrospectively and 2,215 prospectively collected prostate cancer samples from GenomeDx Biosciences' Decipher Genomics Resource Information Database (GRID).

The PAM50 signature identified luminal A patterns in roughly one third of samples in both the retrospective and prospective prostate cancer sets. Some 28 to 33 percent of the samples fell into the luminal B subtype, while 34 to 37 percent had basal-like expression profiles.

When they focused on the retrospective cases, for which clinical outcome data were available, the researchers saw subtype-specific treatment responses. In particular, their results suggested luminal B prostate cancer cases exhibited a significant response to androgen deprivation therapy — a pattern not observed in the other expression-based subtypes.

Even so, the luminal B subtype was also associated with poorer progression-free, metastasis-free, and overall survival times compared with the luminal A or basal-like prostate cancers. At the other end of the spectrum, individuals with the luminal A subtype had better outcomes across the clinicopathologic prognostic factors considered. 

"We did not find the same benefit from [androgen deprivation therapy] for patients with luminal A tumors, perhaps because these patients already have a better prognosis; thus, aggressive treatment may make little difference in the eventual outcome," the authors wrote.

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