The Important Role of Genetics in Ovarian Cancer Treatment

Most people who carry a BRCA gene mutation don't realize they have it until someone in their family is diagnosed with cancer. "This is why it’s important for any new diagnosis of ovarian cancer to undergo genetic testing, to see if they are, in fact, a carrier," says Dr. Adam ElNaggar, a gynecologic oncologist at West Cancer Center in Memphis, Tennessee.

Certain groups of people, like Ashkenazi Jews or those whose families originated in Mediterranean countries, are especially susceptible to these mutations. Anyone with a family history of breast or ovarian cancer should ask their doctor about getting tested. Carrying one of the BRCA genes puts you at increased risk not only for ovarian cancer, but also for breast cancer and for other, less common cancers, Dr. ElNaggar says. Knowing your status could help you and your family stay on top of screenings for these other cancers, too.

Although guidelines recommend that all women with ovarian cancer have genetic testing when they're diagnosed, only a small percentage of women actually do get tested, research finds. Regardless of your age or the type of ovarian cancer you have, testing should be part of your diagnosis. Besides providing valuable information to help your doctor decide on the best treatment for your cancer, knowing that you carry a genetic mutation is valuable for other family members, too. Your immediate family may also benefit from genetic testing. If they find they carry a BRCA1 or BRCA2 mutation it may be recommended that they begin undergoing more frequent screening tests for breast and ovarian cancer, and possibly even consider prophylactic surgery to avoid developing advanced cancer.

Using Genes to Inform Treatment

Gene mutations not only increase the risk of developing ovarian cancer, but they also can make certain types of treatments, like PARP inhibitor drugs more effective.  PARP is an enzyme that cells normally use to repair their damaged DNA. PARP inhibitors block this enzyme to prevent ovarian cancers with BRCA mutations from fixing DNA damage.

Three PARP inhibitors are approved to treat ovarian cancer:

• Olaparib (Lynparza)
• Niraparib (Zejula)
• Rucaparib (Rubraca)

Some women with ovarian cancer have another genetic marker called homologous recombination deficiency (HRD) that makes them particularly good candidates for PARP inhibitors. Ovarian cancers with HRD are already less able to repair their DNA damage, making them easier for the drugs to fight.

However, the American Society of Clinical Oncology (ASCO) released new guidelines recommending PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.

"If you picture your DNA like a railroad track, there are two beams, as well as the cross lattice of woodwork," Dr. El Naggar says. "When a section of that is taken out, your HRD genes would have come in and put that track back together, repairing both tracks. However, when they’re deficient, the body is unable to do that."

When only one track is broken in other words, one strand of DNA PARP enzymes come in and fix the damage so the cancer cell can keep growing. PARP inhibitors block that repair process which prevents the cancer cells from replicating spreading.

Data shows that PARP inhibitors can have the best results in women with a BRCA mutation or HRD, but new studies show that one PARP inhibitor, niraparib (brand name ZEJULA) may provide some benefit for women without these mutations, as well. These drugs can be used initially with chemotherapy and surgery in what is called first-line treatment, or as maintenance therapy to prevent the cancer from returning after treatment.

Genetic testing can benefit you if you've been diagnosed with ovarian cancer, by helping your doctor determine whether a treatment like a PARP inhibitor is likely to be effective against your cancer. It can also inform your family members, enabling them to be more diligent about getting genetic testing and cancer screening.

Learn more about SurvivorNet's rigorous medical review process.

---