Angelina Jolie’s decision to undergo prophylactic mastectomy in the setting of an increased genetic risk of breast cancer (BRCA mutation) didn’t seem extraordinary to most oncologists. For years the relationship between genetic risk and breast cancer has led young women to preemptive surgery.
Despite excellent reconstructive options, these decisions cannot be easy, yet it has become an acceptable standard for those at genetic risk.
Conversely, for men at risk of developing prostate cancer (PCa), prophylactic prostatectomy seems almost irrational for several reasons. First, PCa genetics are heterogeneous and poorly understood.
Additionally, the latency period from histologic cancer to death from disease is measured over years or decades and the relationship between genetic risk and alterations in PCa biologic kinetics is unknown. Finally, the functional and resultant emotional consequences of prostatectomy in young men seem somehow, if unjustifiably, more overwhelming.
Recently, Roger Kirby, MD, Director of the Prostate Cancer Center in London, performed one of the first “prophylactic” prostatectomies in a man with a BRCA mutation as part of a clinical trial involving more than 20,000 men conducted by the Institute of Cancer Research. Men with a BRCA2 mutation have an almost nine-fold increased risk of developing PCa whereas those with a BRCA1 mutation have a greater than three-fold increased risk.
In these men, PCa may be both more aggressive and fatal. According to reports, this patient appears to have had a biopsy consistent with low volume/low risk cancer and made the decision based upon data suggesting he was more likely to die from the disease due on his genetics.
While this case was not performed entirely for prophylactic reasons, it reflects medicine’s growing ability to link genetics to cancer risk. Comprehensive molecular characterization of solid tumors is increasingly common (a “molecular atlas” was recently published in kidney cancer).[i]
When linked to clinical datasets and used in the prospective design and outcomes of clinical trials, this information will revolutionize the way patients and physicians think of cancer risk and, ultimately, how they make medical decisions.
Although it may seem decades away, the kinetics of genomics may be quicker than Moore’s microprocessor law. Recall that the National Cancer Institute set a target of $100,000 for sequencing a human sized genome by 2009 and $1,000 by 2014. We are getting close as several companies claim to be able to sequence 10 billion base pairs for about $5,000-$10,000.
Once available, these data may not only make preemptive prostate surgery more routine, but also make current practices appear uninformed. But isn’t that always the way the future makes the past appear?
- Cancer Genome Atlas Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 2013;499:43-49,