ONCAlert | Upfront Therapy for mRCC

Testing for BRCA and HRD in Ovarian Cancer

Targeted Oncology
Published Online:1:00 PM, Thu November 21, 2019

Bradley J. Monk, MD, FACOG, FACS: One of the biggest discoveries in ovarian cancer is the hereditary breast and ovarian cancer syndrome—and the discovery that the 2 genes most responsible for that phenotype were BRCA1 and BRCA2. We learned that about 17% of patients with newly diagnosed advanced ovarian cancer, including peritoneal and fallopian tube, have germline BRCA mutations. And then another 7% to 10% have somatic mutations.

Here’s the key: We learned that we could test for the BRCA gene in the patient, and then interrogate the entire genealogy and find individuals who were BRCA germline-mutation positive and do a risk-reversing surgery. The current recommendation is that all patients—everyone with epithelial ovarian cancer—be tested for germline mutations early on in the treatment paradigm. This is according to the National Comprehensive Cancer Network and the American Society of Clinical Oncology.

And then in December 2018, we got a companion diagnostic for frontline maintenance with olaparib based on SOLO-1. Now we have to test for not only germline mutations but somatic mutations to find about 25% of the patients who, I think, should be treated with maintenance oral olaparib after response to platinum.

Now we’re beyond BRCA. We’ve learned that in addition to BRCA, there are other genes in the homologous recombination repair pathway that are important not only in prognosis but also in predicting platinum sensitivity and PARP inhibitor sensitivity. That test is called the homologous recombination deficiency [HRD] test. There are 2 commercially available tests: 1 from Foundation Medicine, Inc, which is a loss of heterozygosity and genomic scoring; and then the Myriad test, which is not only loss of heterozygosity, the telomeric allelic imbalances, and large-scale state transitions. So we’ve added to germline testing. We now also do somatic testing and HRD. Then together, we can use the molecular signature to treat our patients and prevent ovarian cancer by identifying those who have these germline mutations in their family and doing risk-reducing surgery.

Transcript edited for clarity.

Bradley J. Monk, MD, FACOG, FACS: One of the biggest discoveries in ovarian cancer is the hereditary breast and ovarian cancer syndrome—and the discovery that the 2 genes most responsible for that phenotype were BRCA1 and BRCA2. We learned that about 17% of patients with newly diagnosed advanced ovarian cancer, including peritoneal and fallopian tube, have germline BRCA mutations. And then another 7% to 10% have somatic mutations.

Here’s the key: We learned that we could test for the BRCA gene in the patient, and then interrogate the entire genealogy and find individuals who were BRCA germline-mutation positive and do a risk-reversing surgery. The current recommendation is that all patients—everyone with epithelial ovarian cancer—be tested for germline mutations early on in the treatment paradigm. This is according to the National Comprehensive Cancer Network and the American Society of Clinical Oncology.

And then in December 2018, we got a companion diagnostic for frontline maintenance with olaparib based on SOLO-1. Now we have to test for not only germline mutations but somatic mutations to find about 25% of the patients who, I think, should be treated with maintenance oral olaparib after response to platinum.

Now we’re beyond BRCA. We’ve learned that in addition to BRCA, there are other genes in the homologous recombination repair pathway that are important not only in prognosis but also in predicting platinum sensitivity and PARP inhibitor sensitivity. That test is called the homologous recombination deficiency [HRD] test. There are 2 commercially available tests: 1 from Foundation Medicine, Inc, which is a loss of heterozygosity and genomic scoring; and then the Myriad test, which is not only loss of heterozygosity, the telomeric allelic imbalances, and large-scale state transitions. So we’ve added to germline testing. We now also do somatic testing and HRD. Then together, we can use the molecular signature to treat our patients and prevent ovarian cancer by identifying those who have these germline mutations in their family and doing risk-reducing surgery.

Transcript edited for clarity.
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