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Personalizing Gynecologic Cancer Treatment

By Mary Jo Blackwood, RN, MPH

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A micrograph of cervical cancer cells ©Tomasz Szul/Visuals Unlimited, Inc./Getty Images

Innovations in technology are generating new patient-tailored prevention and treatment strategies for patients with gynecologic cancer. Matthew Powell, MD, a gynecologic oncologist, uses advanced gene sequencing panels to provide information that helps patients assess their risk for inherited cancers: One panel analyzes 21 genes contributing to increased risk for breast, ovarian and uterine cancers; another analyzes 14 genes that contribute to increased risk for colon cancer, which is closely associated with breast and ovarian cancer.

"Even patients who were negative for BRCA1 and 2 may get a better idea of risk with larger gene panels," Powell said.

"Identifying a specific mutated gene in one of the gene panels can indicate up to a 70 percent risk of developing breast cancer, approximately a 20 percent risk for ovarian cancer and 60 percent for endometrial cancer, depending on the gene mutated," Powell said. He notes that Sheri Babb, MS, a cancer risk genetic counselor, is available to talk with patients who have genetic mutations identified through testing.

Changing Cancer Treatment

Washington University oncologists and pathologists run an active tumor cell genomic profiling service called GPS@WUSTL.

"We can screen cancers for a number of genes, looking for mutations. Test results can guide treatment or steer patients to appropriate clinical trials," Powell said. For example, he is about to launch a drug trial using ponatinib for treatment of endometrial cancer in patients with a specific genetic defect. Those in the treatment group will receive a daily oral dose of the drug, which has been found to repair broken pathways in the defective gene.

"For other endometrial cancer patients, genetic mutations or gene expression data can help us determine whether hormone therapy would be beneficial. In general, oncology is moving away from organ-specific treatment to treating the broken physiologic pathways that create cancer," Powell said. "Drugs already being used effectively for some types of cancer may work for other types that share similar mutations or activated genes." 

Pretesting Cervical Tumors

Physicians know that some patients' tumors do not respond to therapy. In a small study published online in the journal Gynecologic Oncology, researchers tested patients' cervical tumors for vulnerability to chemotherapy before treatment began. Using the currently accepted chemo-therapeutic drug cisplatin, investigators tested tumors from 33 patients with cervical cancer, dividing their tumors into three categories-responsive, intermediate response and nonresponsive-based on how well cisplatin killed tumor cells in vitro.

For responsive tumors, 100 percent of the patients subsequently treated were alive and disease-free after two years. For intermediate response tumors, that number fell to 83 percent. For nonresponsive tumors, only 58 percent of patients had two-year disease-free survival.

"Even though this is a small study, its strength is that it links a lab test of the tumor's chemotherapy response to survival outcomes for patients," said gynecologic oncologist Julie Schwarz, MD, PhD. "Very few cancers have been studied this way, and this is the first such report for cervical cancer."

Larger studies with different types of cervical cancers must be done before treatment recommendations can be made.

"This is not the definitive test," Schwarz said. "But I think our results should prompt investigators to start generating new ideas about how best to treat this disease. The bottom line is that a one-size-fits-all treatment is going by the wayside. As we develop personalized strategies, this is the sort of testing that can guide them."

For more information, visit gps.wustl.edu