Dr Maurie Markman discusses population-based data from the 100,000 Genomes Cancer Programme, focusing on ovarian cancer.
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-- TRANSCRIPT --
Hello. I'm Dr Maurie Markman from City of Hope. I wanted to share with you probably the first of a number of times that I'll be talking about this particular research approach and extraordinary effort. We're seeing some data for the first time that are absolutely fascinating.
We all know about the increasingly important role of precision medicine. Clinical trials have demonstrated the value of therapy that we might give our cancer patients. We also are increasingly learning about the role of germline testing for men and women with a variety of diseases.
The question always comes up about those being select populations. They may be part of clinical trials, for ovarian cancer in particular, where we have shown that one quarter or so of women in the trials may have a BRCA mutation. Some say that once there's a clinical trial and once a woman has ovarian cancer, she may be drawn to those trials because of family history.
The question remains: What about the real world? What about the population that wasn't chosen or didn't elect to choose to participate in the trial? Are we getting a skewed analysis of the likelihood of finding X or finding Y or finding Z?
That's why the large study I'm going to mention now becomes so important. Great Britain made the decision a number of years ago to look at population-based analyses and to look at patients with cancer to see what percentage have a variety of mutations: somatic, only in the cancer, or germline.
The results of this analysis are from the 100,000 Genomes Cancer Programme. It was an initiative to provide whole-genome sequencing for patients with cancer and to look at the wide spectrum of all different cancers to see what can be found and what is relevant on a population basis.
This report, called, "Insights for Precision Oncology From the Integration of Genomic and Clinical Data of 13,880 Tumors From the 100,000 Genomes Cancer Programme," was just published online in early January in Nature Medicine and looks at almost 14,000 tumors.
What is striking here, and what I want to highlight from this paper, are results in ovarian cancer. What this study concluded is incredibly important for oncologists who care for women with ovarian cancer, for patients themselves, and for their families. Again, this was population based, so no patients in this population were selected because they went on a clinical trial.
The investigators showed that 40% of high-grade serous ovarian cancers (the majority of ovarian cancers are high-grade serious) had evidence of homologous recombination deficiencies. That's evidence of serious inability to repair DNA damage.
This would suggest, based on the clinical data, that as many as 40% potentially could benefit from the use of poly (ADP-ribose) polymerase (PARP) inhibitors, which are now widely used, of course. It's not the rare patients, not 1 in 10, not 1 in 5, but 40% of patients will have this deficiency. That's very relevant.
Just as relevant and important, a different aspect of this is that 30% of individuals with ovarian cancer in this population-based analysis had pathogenic germline variants, suggesting that approximately 1 in 3 women with ovarian cancer have a potential germline abnormality. This not only predisposes them to develop a disease but also might be relevant within their family.
Therefore, we get into the question of germline testing of family members and genetic counseling. We have strategies, including screening or surgical approaches that may potentially eliminate or dramatically reduce the risk for ovarian cancer in those individuals demonstrated to have germline abnormalities.
Again, from population-based data, this is a very important observation both for the patient themselves in terms of possible therapy but also very relevant information for that patient's family.
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