CCE Gynecologic Oncology: Duke University Medical Center

Duke

University Medical Center
Durham

, North Carolina

Some might call the discovery of BRCA1 and BRCA2 breast and ovarian cancer susceptibility genes the most significant genetic breakthrough in ovarian cancer research to date. But the physician-researchers at Duke Medical Center are looking deeper into the genome to find other possible causes of ovarian cancer.

Since ovarian cancer is the fifth leading cause of cancer deaths among women, these  lines of research – along with providing  leading-edge diagnostic tools and treatment paradigms, such as robotic-assisted laparoscopic  – is what makes Duke Medical Center’s division of gynecologic oncology a Clinical Center of Excellence.

Inherited mutations in the BRCA1 and BRCA2 genes are responsible for only about 10 percent of ovarian cancers, but a woman who carries one of these mutations has a very high likelihood of developing the disease in her lifetime.  Duke researchers are looking for additional  polymorphisms that might also increase risk, albeit less dramatically.  However, because these polymorphisms may be much more common than BRCA1 and BRCA2 mutations, they could account for as many, if not more, ovarian cancers.  The search for relevant polymorphisms focuses both on genes that are thought to play a role in ovarian cancer development, such as those in DNA repair and hormonal pathways, as well as on whole genome scanning approaches. 

The ongoing North Carolina Ovarian Cancer Study was initiated in 1999 and more than 1,200 women  with the disease have been enrolled. Their DNA and ovarian cancer risk factor profiles are compared to controls without the disease.   “We’re looking for polymorphisms that are more common in women with ovarian cancer than in women who don’t have ovarian cancer,” explains Andrew Berchuck, MD, director of the Division Gynecologic Oncology.

“A genetic polymorphism might increase your risk of ovarian cancer only slightly. So, if your baseline lifetime risk of ovarian cancer is 1.5 percent, it might only raise your risk to 2 or 3 percent.”  The ultimate goal, Dr. Berchuck says, is to identify women with a genetic susceptibility to ovarian cancer.  Women deemed  at increased risk due to genetic factors or other epidemiological risk factors, such as not having had children, would be the group most likely to benefit from screening and prevention approaches.  Or these women might be advised to undergo prophylactic salpingo-oophorectomy, as now is performed often on women who carry BRCA 1 or BRCA2 mutations.

Duke researchers also have used microarray analyses of ovarian tumors to learn more about the pathways and genes that are altered.  These studies of the molecular differences between cancer types  provide clues that open the possibility of developing personalized treatment with pathway-specific oncolytic agents.  “We look at expression of thousands of genes to try to determine patterns that correlate with response to different types of treatment,” Dr. Berchuck says.

Through this research, Duke investigators along with their colleagues in Duke’s Institute for Genome Sciences and Policy found the src oncogenic pathway was most often overexpressed in cancers with the worst outcome. That led to the development of a genomic test – that predicts long-term survival after conventional chemotherapy with  about 90 percent accuracy.

Clinical trials are under way to move this treatment paradigm forward.  Such research is just one component of what makes Duke’s gynecologic oncology division stand out.

“Our program is notable because we offer cutting-edge clinical care, outstanding fellowship training, and are actively involved in clinical trials,” says Dr. Berchuck. This includes the national cooperative trials of the Gynecologic Oncology Group  as well as in-house trials. 

“It has been gratifying to see the emergence of minimally invasive surgery as the dominant paradigm,” Dr. Berchuck says.  "With the extensive experience we have accumulated, we are now able to approach about two-thirds of our major cases using minimally invasive surgery.  This may be either by way of traditional laparoscopy or robotic surgery.  It is gratifying to witness the resulting rapid recovery and amazing cosmetic results.”

“In summary, at Duke University we have a very active molecular research program where we’re trying to push the envelope as we work towards better screening, prevention and treatment,” says Dr. Berchuk. "Clinically, we are defined by the comprehensiveness of what we do, and offer the latest in cutting-edge clinical care and research trials.”