Can a Genetic Test Help Personalize Prostate Cancer Treatment for Men?

By Joseph Longo

Prostate cancer is the most commonly diagnosed cancer among Canadian men, with 1 in 8 men expected to develop the disease in their lifetime. Thanks to advances in early detection and screening, prostate cancer treatments have significantly improved over the years and, if caught early, the 5-year survival rate is nearly 100%. Despite these advancements, over 4000 men still die of prostate cancer each year, making it the third-leading cause of cancer-related death in men.

Treatment for prostate cancer can vary depending on the stage of the disease at diagnosis and how likely the disease is to grow and spread to other parts of the body. Men diagnosed with low-risk prostate cancer tend to go on ‘active surveillance’, where regular check-ups and testing are recommended to closely monitor disease progression. This avoids the need for invasive and aggressive therapies with unwanted side effects in patients with small, slow-growing and asymptomatic disease. Men at higher risk of disease progression are treated with a combination of surgery, radiation therapy and/or hormone therapy. While these lines of therapy are initially effective, approximately one-third of patients will have their cancer return in a more aggressive and lethal form. We currently do not understand why some patients respond to these forms of therapy, while others do not. If we can predict treatment failure, then we can spare patients from unnecessary and ineffective treatments, and potentially offer more personalized and effective treatment options at diagnosis.

A recent study led by a team of researchers from Toronto and Melbourne found that prostate cancer patients with an inherited mutation in the BRCA2 gene tend to have more aggressive and advanced forms of the disease. Mutations in the BRCA2 gene, and its relative BRCA1, are typically associated with an increased risk of breast and ovarian cancers. You may remember the news headlines from 2013 when actress Angelina Jolie underwent a preventative double mastectomy after testing positive for a BRCA1 mutation. What people are less aware of, however, is that inherited mutations in the BRCA2 gene also increase the risk of developing prostate cancer. BRCA1 and BRCA2 are important players in the cell’s ability to repair damage to its DNA. When mutations in these genes prevent them from working properly, it increases the chances of developing cancer.

Prostate tumours in men with an inherited mutation in BRCA2 tend to be more aggressive and have a higher chance of spreading to other parts of the body. These patients are also more likely not to respond to first-line prostate cancer treatments, including surgery and radiation therapy. While the chances of having an inherited BRCA2 mutation are low (less than 1% of the population), testing for this mutation at diagnosis could spare men who are mutant BRCA2-positive from going through therapies that are likely to fail. Instead, these patients may benefit from more aggressive treatment upfront, including chemo- and targeted drug therapies.

This article was written by Joseph Longo. Joseph is currently pursuing a PhD in the Department of Medical Biophysics at the University of Toronto. He studies how statins can be used to treat cancer. To learn more about Joseph and his research, check out our members page.

References

  1. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2016. Toronto, ON: Canadian Cancer Society; 2016.
  2. Taylor et al., 2017. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nature Communications. doi: 10.1038/ncomms13671.
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