Study indicates that genomic test may personalize therapy for patients.
A test commonly used in breast cancer has been found to also identify which patients with aggressive prostate cancer will benefit from hormonal therapy, according to a study led by scientists at UC San Francisco and the University of Michigan.

While hormone therapy has been used successfully to treat many prostate cancer patients, until now, researchers have been unable to predict which patients would benefit from early initiation of this therapy following surgery. The study, conducted by a team of researchers at 11 medical centers nationwide and in Canada, demonstrates the first new way to select the best treatment for specific patients.

In the study, which appeared in the journal JAMA Oncology, the researchers divided prostate tumors into three subtypes based on genetic patterns. Their results reveal that starting hormone treatment after surgery prevents the spread of the tumor in only one of the three types, known as luminal B, a particularly aggressive form that affects about one–third of those with the disease.

Hormone therapy carries significant side effects, so knowing which patients are likely to benefit from it can focus treatment on the right patients at the appropriate time, while sparing the others of increased risk of fatigue, sexual dysfunction, osteoporosis, diabetes and other conditions.

If confirmed, patients with the luminal B subtype could be selected for early initiation of hormone therapy, which would allow for treatment intensification for patients most likely to benefit from it, said Felix Feng, MD, a radiation oncologist with UCSF Health and a senior author of the study.

The test, called PAM50, has been used for over a decade to identify which breast cancers are the best candidates for hormone treatment. But no such screen has been available for prostate cancer, Feng said. The new research shows that PAM50 can also distinguish between the three prostate cancer subtypes.

Feng’s co–senior author on the research paper, Daniel Spratt, MD, a radiation oncologist at the University of Michigan, commented on the potential of the biomarker to distinguish between the three prostate cancer subtypes: luminal B, luminal A and basal.

The retrospective study focused on 1,567 prostate cancer samples from high–risk patients who had undergone radical prostatectomy. The scientists identified the three distinct gene expression profiles that define the three cancer subtypes and confirmed the finding in another 6,300 prostate cancer samples.

They determined that luminal B disease was the most aggressive, with metastases recurring in about half of the patients over 10 years, compared to about one quarter of the patients with the luminal A or basal subtype.

They found that ADT treatments were more effective with luminal B tumors and may even have worsened prognosis in the other types of tumors – a finding that would need to be confirmed with a prospective study and to firmly establish the biomarker finding as a diagnostic tool to guide treatment, said Feng.

Feng and Spratt will co–lead a large, National Cancer Institute–funded prospective clinical trial involving as many as a hundred clinical research sites, using the PAM50 assay to identify patients by their cancer subtype, and then randomly assign them to treatment with radiation and a placebo or radiation and hormone therapy treatment.