A 57-Year-Old Woman With Ovarian Cancer - Episode 2

Molecular Testing: Ovarian Cancer

An oncologist explains the importance of molecular testing in ovarian cancer and the implications of testing on treatment selection.

Lyndsay Willmott, MD: Molecular testing in ovarian cancer is very important—genetic testing, namely. For many years, we used an algorithm to help determine who should be tested, but now we recognize that every woman should be tested for genetic abnormalities regardless of any other prognostic or historical factor, such as age or family history. These types of things no longer matter. Anyone diagnosed with an ovarian fallopian tube or primary peritoneal cancer should have genetic testing. Certainly, there are a number of strategies that can be utilized to determine how you perform this testing. This could mean that you start with germline testing to assess for germline mutation. The majority of providers now recognize that doing BRCA-specific germline testing is probably not the best way to do this. We should be utilizing panel testing, which can capture a number of the other homologous recombination proteins that can be abnormal in the setting of ovarian cancers. Other providers will start with somatic testing, which can test the tumor to evaluate for the presence or absence of these mutations.

The important thing to remember is that if the testing is negative, that’s not where you should stop. If you have a negative germline test, then perhaps you should subsequently reflex to a somatic test. Similarly, if your somatic testing is negative, then you should consider reflexing to germline testing. Somatic testing can also be a good way to capture patients who have a germline abnormality. If you detect a BRCA mutation on a somatic test but the patient hasn’t undergone germline testing, then you should certainly do germline testing to see if that mutation is originating from a germline source. The important difference is that germline testing obviously has implications for this patient. It could mean that she has higher risk of other kinds of malignancies. Also, very importantly, it would trigger us to recommend testing for her family. You’d want to make sure we’re capturing any family members who have these mutations so that we could then intervene to prevent them from developing a malignancy.

Last but not least, it’s important to consider doing homologous recombination deficiency testing. There are a number of tests available, including panels that can assess and assign a homologous recombination deficiency score, or presence or absence of homologous recombination deficiency. Some providers are starting with that testing first because it captures the greatest pool of patients. We estimate that at least 50% of our patients with ovarian cancer have homologous recombination deficiency. If we start with assessment for homologous recombination deficiency, we can subsequently reflex back to the other types of testing, including germline mutational testing. The truth is that we have a number of ways of testing for these abnormalities, and all patients should be getting this testing. The algorithm that you use can be determined by your preferences or your practice’s. It’s important that you’re applying that to all patients so we’re not missing mutations or deficiencies when they occur.

Another important question is whether this testing should be repeated after a patient has been diagnosed with a recurrence. There’s importance to consider that. Certainly, you could consider repeating this testing to see if the patient has developed a BRCA mutation. Occasionally, we see the patients in the setting of recurrence actually have subsequently developed a somatic mutation. That may have implications for how you counsel a patient, for how she may respond to certain kinds of therapy, and it may certainly have implications for choices of therapy. It’s important to consider retesting the tumor after the time of diagnosis.

Case Overview: A 57-Year-Old Woman With Ovarian Cancer

Initial Presentation

A 57-year-old woman presented with progressive abdominal discomfort and bloating, early satiety, new-onset constipation, and unintentional weight loss

PMH: postmenopausal; hypertension—medially controlled; osteoarthritis

PE: right lower quadrant tenderness on palpation

ECOG PS 1

Clinical work-up

Pelvic exam with ultrasound showed a ~4.5-cm right ovarian mass

Chest/abdomen/pelvis CT with contrast revealed a right adnexal mass with lymph node involvement and ascites

Paracentesis (1200cc) cytology confirmed high-grade serous epithelial ovarian cancer

Germline molecular testing: BRCA1/2wt

Somatic testing: BRCA1/2 negative; HRD positive

CA-125, 360 U/mL

Diagnosis: Stage III, high-grade serous epithelial ovarian cancer

Treatment

Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0

Carboplatin/docetaxel q3 weeks for 6 cycles; CA-125 normalized; CR

Bevacizumab maintenance

At 2 years post chemotherapy, patient experienced abdominal bloating and pain, nausea and vomiting and progressive fatigue; CA-125 increased; imaging revealed progressive retroperitoneal adenopathy suggestive of recurrent disease; not deemed a candidate for secondary surgery

Rechallenged with carboplatin/docetaxel q3 weeks for 6 cycles; PR; predominantly enlarged lymph nodes

Rucaparib single-agent maintenance 600 mg bid

Patient developed clinically significant thrombocytopenia; dose reduced to 500 mg and patient remained on treatment until disease progression

Transcript edited for clarity.