Expert Perspectives on Treating Recurrent Ovarian Cancer - Episode 3

Molecular Testing in Ovarian Cancer

March 26, 2021
Shannon Westin, MD

Shannon Westin, MD, analyzes the role of molecular testing in newly diagnosed ovarian cancer.

Shannon Westin, MD: The easy answer regarding testing for a newly diagnosed ovarian cancer is that we should be getting, at the very least, genetic testing for all these patients, specifically utilizing testing panels that let us check for BRCA1 and BRCA2. Many of us are increasing our use of “panel testing,” where we study upward of 26 genes that can be involved with hereditary cancer. It is a high-yield situation, even in patients who are greater than age 50 years old and have no family history of disease. We can identify hereditary syndromes, and obviously that can affect the type of treatment that our patients benefit from and that they might receive.

Molecular testing is increasing as well, because we know that patients who have a somatic BRCA mutation, or a mutation that is only in the tumor, have just as much benefit from these therapies as those with a germline mutation. There are many ways to skin this cat, so to speak. In our institution we do start with the germline testing. Then we refer to somatic testing if the germline is negative. Some institutions and some companies offer the opportunity to do both tests at once, and that is certainly reasonable. What we try not to do is conduct only somatic testing because if you do, you are going to miss about 5% of patients who have a germline mutation. Their tumor does not show that somatic mutation, so we try to utilize both those strategies.

Finally, the last testing that you can get—you can even pair this with your somatic testing—is testing for homologous recombination deficiency. There are several companies that offer that commercially, and they do it in slightly different ways, but generally they are looking for something called loss of heterozygosity. They also look for other factors that may contribute to genomic instability. That measure of genomics in stability gives us a sense of the likelihood that this patient might benefit from a PARP inhibitor. This test is not necessarily required, but it does provide a way to potentially guide your therapy. It is specifically helpful when counseling your patient on the likelihood of benefiting from a PARP inhibitor. Typically, I will get that germline testing, followed by a reflex to somatic testing with a test that offers me a homologous recombination deficiency score as well. I really think, from a prognosis standpoint, that it is very important to understand how the patient might respond to treatment when I identify those hereditary syndromes, because that is going to have an impact on the family as well.

Transcript edited for clarity.

Case: A 68-Year-Old Woman With Recurrent Ovarian Cancer

Initial Presentation

  • A 68-year-old female presented with abdominal bloating, discomfort and decreased appetite
  • PMH: unremarkable, postmenopausal; no known family history of cancer
  • PE: abdominal distention, right lower quadrant tenderness on palpation

Clinical work-up

  • Pelvic exam with transvaginal ultrasound showed a right ovarian mass
  • Chest/abdomen/pelvis CT with contrast revealed a right adnexal 4-cm mass, inguinal lymph node involvement and ascites, no pleural effusion
  • Lymph node, adnexal mass biopsy, and paracentesis (1500 cc) cytology confirmed high-grade epithelial ovarian cancer
  • Germline molecular testing: HRD+, BRCA1/2-
  • CA-125, 385 U/mL
  • Diagnosis: Stage 4, high-grade epithelial ovarian cancer
  • ECOG PS 0


  • Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
  • IP/IV paclitaxel/carboplatin; PR
  • Followed by niraparib maintenance