The Role of Molecular Testing in Ovarian Cancer

EP: 1.Case Presentation: A 59-Year-Old Woman with Ovarian Cancer

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Chirag A. Shah, MD: When we evaluate the role of molecular testing in patients with newly diagnosed ovarian cancer, I would certainly say that this has been an evolving area of research and guideline-based care. Approximately 5 years ago, the National Comprehensive Cancer Network [NCCN] recommended germline testing for all patients who were diagnosed with newly apparent ovarian cancer, fallopian tube cancer, primary peritoneal cancers; these cancers are all lumped together under the term ovarian cancer. More recently, the NCCN has also approved and recommended that these women undergo somatic testing. The reason behind this is that it has become apparent if you only obtain one test, whether it’s your germline or somatic test, you’re going to miss at least on the order of 5% of patients who have a mutation, whether it’s one that they inherited, a germline mutation, or somatic, which is tumor based.

The timing of testing has also been a rapidly evolving place. People have hypothesized about whether patients should undergo reflexive testing, for example, obtaining one test and if that’s negative, obtain the second test. Some people approach this in either fashion, obtaining the germline testing first or obtaining the somatic testing first. I think some of it becomes a question of what’s available at whatever institution you practice at. However, our approach has been to obtain both sets of testing; it provides the greatest amount of information. There’s information about the genomic signature that you can get from the somatic test that’s not provided by the germline test. As we’ve evolved to understand that genomic scar in the form of homologous recombination, it is a phenotypic biomarker for how these patients may do and how they may respond to future treatment. Essentially, molecular testing can be used to guide treatment; it can be used to provide prognostic information. It’s important to know both the germline portion so that the patient knows for herself and for her family what their inheritable risks are, but also knowing the genomic signature of the tumor to help explain what her response to therapies might look like. It could help explain what led to the development of this cancer for these patients, or to potentially identify, in the case of patients who are homologous recombination proficient, those who are at the highest risk of recurrence.

We have a protocol that’s taken about 2 years to come into existence through the various steps along the way. We’re evaluating this in the form of a clinical trial, where we’re obtaining germline testing using an online app to connect to patients through Ambry [Genetics] to get their germline results. At the same time, we’re using the molecular genomics laboratory at our facility and obtaining HRD [homologous recombination deficiency] testing in the approved process. Essentially for all intents and purposes, we’re collecting data while we obtain 3 sets of testing. The somatic testing is 2 parts, the true genomic testing, but also the formal HRD testing. Then the patient goes through the germline process and has an informational tool or an app that they can download. For patients who are unable to download the app, there is in-person and telephonic approaches to get counseling. That is our approach at our institution.

Transcript edited for clarity.