Genetic Testing, Treatment Advances Offer 'Hope on the Horizon' for Ovarian Cancer

Understanding the inherited biology of ovarian cancer tumors will help to continue to prevent and treat, and one day cure the disease, Angeles Alvarez Secord, M.D., MHSc, said during a presentation at the 2018 National Ovarian Cancer Coalition.

Among the estimated 1.7 million estimated new cancer cases in the US this year, more than 22,000 of them will be ovarian cancer diagnoses — at a median age of 63 years. As the 11th most common cancer in women, approximately 14,000 individuals will die of the disease this year.

However, there is hope: The incidence of ovarian cancer in the US has slowly fallen over the last 20 years. For example, in 2013, less than 200,000 women are living with ovarian cancer across the nation. Similarly, mortality from the disease has also declined.

Some risk factors for the disease include personal and family history, genetic predisposition and other factors like smoking, menopausal hormone therapy, excess body weight and adult height. However, factors that may decrease a woman’s chances for ovarian cancer are tubal ligation (getting one’s tubes tied), pregnancy and total lifetime use of oral contraceptives.

One interesting aspect of the disease: It is not one-size-fits-all. “One of the things about ovarian cancer is that we have learned it doesn’t just fit under one umbrella, not one ovarian cancer is the same. We now know that there are several histologic subtypes,” said Alvarez Secord, who is an associate professor in the division of gynecologic oncology at Duke University Medical Center.

These include high-grade serous, clear cell, endometrioid, low-grade serous mucinous, and a subgroup of other ovarian cancers that make up a small percentage of the disease. When low- and high-grade serous ovarian cancers are broken up, each has specific molecular alterations that may impact treatment decisions. For example, women with low-grade disease may have a KRAS, NRAS or BRAF mutation or HER2 amplification; on the other hand, high-grade serous disease may have TP53 or BRCA1/2 mutations or chromosomal instability (also known as lynch syndrome).

“The exciting part here is once you understand the underlying biology of the tumor, you can then target your therapies,” added Alvarez Secord.

Because of this, genetic testing has become more prevalent in recent years. “What is surprising to people is you see these mutations across the board in a variety of ovarian cancers, and that is really important to understand who should be testing. It is not just someone who has high-grade serous type, anyone who has ovarian cancer should be tested for these mutations.”

“Approximately 20 to 25 percent of ovarian cancer patients have a deleterious germline or somatic mutation in the BRCA1 or BRCA2 gene,” she added.

If a woman tests positive for a germline BRCA or other high-risk mutation, this result could have predictive, prognostic and therapeutic implications. It may also detect women’s cancer risks in other organs while also identifying relatives that should also be tested — known as cascade testing. Meanwhile, for women who may test with no germline mutation, genetic testing would help them to avoid unnecessary surgical risks, added Alvarez Secord.

“The most exciting thing for us right now is being able to identify these genes that increase your risk, being able to implement appropriate screening procedures, doing the surgery and the cascade testing, and preventing these diseases from even occurring. And we can do that — right here, right now,” she said.

Following genetic testing, and a possible ovarian cancer diagnosis, Alvarez Secord also highlighted the importance of patients understanding what questions they should be asking their health care teams.

In the staging and diagnosis phase, women should ask whether they should have surgery or chemotherapy first; how they should make that decision; about how surgery will be performed; and what they should expect from surgery.

Similarly, in determining their treatment options, women must consult their physicians on the type of treatment; if they are eligible to enroll in a clinical trial; if they have a tumor marker that can be used to direct therapy toward treatment like a PARP inhibitor, Avastin (bevacizumab) or immunotherapy; and what the benefits of these treatments are compared with the possible side effects.

“Understanding the inherited biology of these tumors, diving down in to the DNA, is going to enhance our understanding so that we can hopefully develop more individualized/personalized approach to caring for women with ovarian cancer, and for all people with cancer in terms of preventing, treating and curing these diseases,” said Alvarez Secord.