Scientists identify biomarkers to guide hormone therapy for prostate cancer

May 17, 2017 by Elizabeth Fernandez
Credit: UCSF

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 has been used successfully to treat many 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 appears today 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, a radiation oncologist with UCSF Health and a senior author of the study.

"We've clearly shown that there are different molecular subtypes of prostate cancer and that a test widely used in breast cancer can also potentially be used to help individualize therapy for prostate cancer patients as well." said Feng, a UCSF associate professor of Radiation Oncology, Urology, and Medicine, who specializes in the treatment of high-risk, aggressive prostate cancers. He is also a member of the UCSF Helen Diller Family Comprehensive Cancer Center.

Starving tumors of hormones

The hormone treatment is known as androgen-deprivation therapy, or ADT. Just as estrogen has been found to promote breast cancer growth, male sex hormones called androgens—notably testosterone—stimulate prostate cancer. As in treatment, depriving cancer of the critical sex hormone can starve some .

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.

"Ultimately, our goal is to find the right treatment for the right patient at the right time," said Feng. "Using the PAM50 test may allow us to take the first step towards this goal, in the setting of hormone therapy for prostate cancer patients treated with surgery."

Feng's co-senior author on the research paper, Daniel Spratt, 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.

"Prostate cancer has seen a recent surge of both investigational and commercially available prognostic biomarkers," Spratt said. "Luminal and basal subtyping can be added to a very short list of predictive biomarkers in prostate cancer to truly personalize treatment for prostate cancer patients."

A provocative and hopeful study

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 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 subtype, and then randomly assign them to treatment with radiation and a placebo or radiation and treatment.

"Our research published today, while very provocative, needs to be validated in this prospective study," the researchers said. "We're hopeful that the biomarkers will prove to be a robust predictor of success, so we can increase survival of even the most aggressive cases and at the same time limit to those most likely to benefit from it."

Explore further: Trial shows responses to abiraterone acetate in some prostate cancer patients with initial hormone induction failure

More information: Shuang G. Zhao et al. Associations of Luminal and Basal Subtyping of Prostate Cancer With Prognosis and Response to Androgen Deprivation Therapy, JAMA Oncology (2017). DOI: 10.1001/jamaoncol.2017.0751

Related Stories

Trial shows responses to abiraterone acetate in some prostate cancer patients with initial hormone induction failure

April 5, 2017
Patients with metastatic prostate cancer whose PSA levels remain high despite initial hormone treatments have historically had poor prognosis, with survival typically in the 1-2 year range. Results of a 40-person clinical ...

New treatment regimen extends life for some men with recurrent prostate cancer, study finds

February 1, 2017
Adding hormonal therapy to radiation treatment can significantly improve the average long-term survival of men with prostate cancer who have had their prostate gland removed, according to a new Cedars-Sinai study published ...

Markers for prostate cancer death can identify men in need of more aggressive treatment

January 12, 2017
Prostate cancer (PC) is the second leading cause of male cancer death in the United States with an estimated 26,000 deaths in 2016. Two-thirds of all PC deaths observed in the US are men with localized disease who developed ...

Cardiac risk a factor when considering hormonal therapy for prostate cancer

September 28, 2016
In a recent study, a Yale Cancer Center team determined that men who received hormonal therapy for prostate cancer had a net harm if they had a prior history of a heart attack. The findings were presented September 28 at ...

Three novel intrinsic subtypes of prostate cancer identified

September 26, 2016
In the largest study of its kind to date, researchers have identified and validated three distinct molecular subtypes of prostate cancer that correlate with distant metastasis-free survival and can assist in future research ...

Study finds marker of aggressive prostate cancer

August 3, 2016
The level of a specific molecule present in prostate tumors is an indicator of whether the cancer is aggressive and likely to spread, according to new research from Washington University School of Medicine in St. Louis.

Recommended for you

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.