Ovarian Cancer: Considerations for Molecular Testing
Insights From: Oliver Dorigo, MD, PhD, Stanford University Medical Center; Whitney Graybill, MD, MS, Medical University of South Carolina; Matthew Powell, MD, Washington University School of Medicine
Oliver Dorigo, MD, PhD: Cell-free DNA via liquid biopsy is technology that is still under development. It’s being offered by several laboratories. In general, we see a lesser number of genes being tested by liquid biopsies. I do believe that this is, in the future, a technology that we can use in our patients. The great advantage of liquid biopsies is obviously that patients do not have to undergo a biopsy of the tumor tissue. And if we get a representative somatic mutation panel from liquid biopsy, this will hopefully in the future allow us to follow patients much closer for the development of new mutations in their tumor. The development of certain versions of mutations, for example BRCA1 and BRCA2, might indicate resistance to new therapies, including PARP inhibitors.
Matthew Powell, MD: Biomarkers that are predictive for response to PARP inhibitors include how a patient responded to platinum. If you look at the indications for these drugs, you see that patients typically responded to platinum twice and usually had a complete response followed by at least a complete or partial response. That in and of itself is a biomarker that helps us determine who is most likely to benefit from these drugs.
We could also use BRCA1 and BRCA2 testing and the BRCA-like genes, which can be other genes within that category, but also specialized tests such as homologous recombination deficiency assessment. There are a couple different commercial tests out on the market at this point. But in reality, now with the indications, it becomes a little less important to do this testing. Really using a patient’s own biologic status, how they responded to their platinum, may help us triage them for the appropriate use of the drug.
Oliver Dorigo, MD, PhD: In general, all of our national organizations do strongly recommend germline testing of patients who are diagnosed with ovarian cancers. If we find predisposing genetic mutations in those individuals, we highly recommend that family members are being tested for those mutations. If we find mutations in family members, we can advise those patients to undergo the appropriate screening procedures. We do perform prophylactic removal of the ovaries and fallopian tubes, which is recommended after the age of 35 for patients with BRCA1 or BRCA2 mutations. We have shown in studies over the last decade that the prophylactic removal of fallopian tubes and ovaries indeed can greatly decrease the risk of developing ovarian cancer. And ultimately, if you identify those patients at high risk, we’ll hopefully decrease the incidence of ovarian fallopian tube cancer over time.