Medical Advances in Ovarian Cancer

A 67-year-old woman goes to her primary care physician concerned about abdominal pressure, bloating, and pain. The new symptoms were sudden, severe, and have been ongoing for several days. A blood test followed by an ultrasound revealed a mass in the patient’s abdomen, the result of late- stage malignant ovarian cancer (OC). About half of patients diagnosed with OC are age 63 or older. It’s a disease that is most often caught in its later stages, when it’s more difficult to treat. About eight of 10 cases are diagnosed when the cancer has spread outside the ovaries. Unlike breast and cervical cancer, there are no reliable screening tests that detect OC. There are, however, newer treatments and diagnostic tests that may improve outcomes and offer prevention options. Researchers are also gaining insights into catching the disease earlier.

Warning Signs

While the aforementioned patient’s symptoms can point to any number of conditions, there are clues that suggest the possibility of something serious.

“When symptoms are persistent, new, and above and beyond your baseline experience of these symptoms, it’s time to see your primary care doctor or gynecologist,” says gynecologic oncologist, surgeon, and researcher Sanaz Memarzadeh, MD, PhD, UCLA Division of Gynecologic Oncology.

Defining and Diagnosing Ovarian Cancer

The ovaries consist mainly of three types of cells: epithelial, germ, and stromal cells. Each of these cells can form a different type of tumor that may or may not become cancerous. The term carcinoma describes a category of cancer that develops from epithelial cells that line various organs and structures, including the ovaries/fallopian tubes, prostate, liver, and kidneys. Carcinomas are the most common type of cancer. Up to 90 percent of malignant ovarian cancers are carcinomas, and many likely arise from the fallopian tube.

The Value of Genetic Testing

An extensive family history of ovarian and breast cancer is a good reason for genetic testing. BRCA1 and BRCA2 gene mutations are most often associated with breast cancer, but they also predispose patients to ovarian cancer. It is estimated that about 44 percent of women who inherit a BRCA1 mutation and about 17 percent of women who inherit a BRCA2 mutation will develop OC by the age of 80.

If a woman diagnosed with epithelial OC has not been genetically tested, Dr. Memarzadeh says there is value in doing so.

“If a patient has a BRCA mutation, there could be increased risk for other types of cancer, such as melanoma, breast, and pancreatic,” she says. “Because the mutation is hereditary, there are implications for siblings and children. There is a 50 percent chance of passing the gene on to children. Genetic testing also informs treatment. For example, PARP inhibitors have been shown to arrest the growth of cancer cells when a BRCA mutation is present. These drugs have been helpful in both maintenance therapy and for recurrent cancer in patients with BRCA-associated ovarian cancer.”

PARP inhibitors are among the most exciting and newer therapeutic treatments. Advances such as these enable physicians to treat according to a patient’s genetic make-up. New treatments get their start in basic science labs, such as the G.O. Discovery Lab (www.godiscoverylab.com) founded by Dr. Memarzadeh. She, her team, and collaborators at UCLA are in the pre-clinical phase of targeting mutant p53 protein, which results from genetic changes commonly seen in ovarian and other cancers.

“It plays a central role in initiating epithelial ovarian cancer, and there is evidence to suggest it induces resistance to standard chemotherapies, such as carboplatin,” explains Dr. Memarzadeh. “We are working to restore the normal function of mutant p53 protein with the hope of reinstating sensitivity to chemotherapy in a subset of tumors.”

Advancing Surgical Treatment

Surgery to remove the ovaries is the go-to preventive strategy upon discovery of a genetic mutation. Once diagnosed with OC, surgery has also been the traditional first course of treatment. But evolving data show that patients who have extensive disease difficulties may benefit when chemotherapy is used to shrink the tumor and then surgically remove it. After surgery, chemotherapy usually entails a combination of drugs meant to destroy any remaining cancer cells. In some cases, Dr. Memarzadeh says she has had successes with chemotherapy as the first course of treatment, and recommends individualizing treatment for each patient.

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