Annual Report - 2005-2006
An Ounce of Prevention
By Scott Merville
Better diet. More exercise. Tobacco avoidance. When the issue is disease prevention, these important general categories come swiftly to mind.
Prevention at M. D Anderson is more sweepingly defined, yet focuses on crafting personalized approaches by tapping advances in medical and molecular research.
“Prevention is broad,” says Bernard Levin, M.D., vice president and head of the Division of Cancer Prevention and Population Sciences. “It’s not just prevention of cancer development, but includes advances in early diagnosis and treatment that reduce suffering and mortality from the disease.”
Levin anticipates a day when people will get a specific assessment of their personal risk of developing cancer based on their history, lifestyle and habits, exposure to carcinogens and genomic information. “That will lead to personalized preventive measures.”
What’s my risk?
“Physicians have little to help them predict risk of lung cancer in their patients who are, or have been, smokers,” says Margaret Spitz, M.D., chair of the Department of Epidemiology. “Even a history of heavy smoking doesn’t always help since only a fraction of long-term smokers develop lung cancer.”
Understanding factors that favor one smoker and condemn another would enhance early detection and open new treatment possibilities.
Researchers are building risk-assessment models using clinical information available to physicians. For former smokers, they found that length of time they had stopped smoking, history of emphysema, no prior hay fever, dust exposure and family history are risk predictors. For smokers, the model includes intensity of smoking and asbestos exposure. For those who never smoked, passive exposure to tobacco smoke and family cancer history count. This model correctly classifies about 70% of lung cancer cases. The next step is to heighten its accuracy by incorporating genetic variation data into the model.
Genetic variations are known to raise a person’s risk for cancer, but can they also predict how a patient’s disease will unfold?
Xifeng Wu, M.D., Ph.D., professor in the Department of Epidemiology, examined genes that are vital to the structure of telomeres, which cap and protect the ends of chromosomes. She and her colleagues found that lung cancer patients with high expression of one gene (RAP1) in their tumors had a median survival of 51 months versus only 15 months for those who didn’t.
“It’s remarkable, because in lung cancer research, if you find something that adds three months, that’s significant,” Spitz says. RAP1 provides an intriguing target for therapy and researchers are refining its predictive value.
Wu, Spitz and their colleagues also reported that genetic variations known to raise lung cancer risk, because they affect the capacity to repair tobacco-induced DNA damage, benefit patients treated with platinum-based chemotherapy.
A robust repair system fixes damaged DNA that fuels cancer growth. A weak system allows cancer to develop. Yet the team found that patients with advanced lung cancer who received platinum-based chemotherapy lived nearly six months longer if they had genetically less efficient DNA repair than patients with efficient repair. Efficient DNA repair treats platinum’s attack on cancer the same way it treats DNA damage caused by tobacco carcinogens — it removes it, neutralizing the drug.
“This genetic variation has the potential to guide treatment,” Spitz says. “Those with efficient DNA repair may need other therapy, or perhaps a more intense dose of platinum.”
Tobacco doesn’t just attack the lungs. It’s involved in cancers of the head and neck, esophagus, pancreas and more. Many smokers quit after diagnosis, but some have difficulty breaking nicotine’s grip, undermining their treatment.
Last year, the Department of Behavioral Science introduced the Tobacco Treatment Program, which by late fall was serving 414 patients who cumu-latively had visited 2,625 times.
“It’s a free, comprehensive program for M. D. Anderson patients who use tobacco or who have quit within the last year, because we need to prevent relapse,” says program director Paul Cinciripini, Ph.D., professor in the Department of Behavioral Science.
The program, funded by the Texas Tobacco Settlement Fund, offers counseling and medications that block or replace nicotine, which enhances neurotransmitters that elevate mood. “There also are important psychological variables to address: stress, mood, anxiety and depression,” Cinciripini says, so antidepressants are employed.
Cinciripini now leads a clinical trial assessing how two common antidepressants affect a patient’s mood and whether genetics plays a role in their effectiveness. Cinciripini and colleagues reported last year that the new antidepressant venlafaxine helps some smokers quit when combined with nicotine replacement and counseling.
Drugs that prevent
Chemoprevention involves finding and testing drugs that might stop cancer from developing at all.
Levin led an international study showing that the anti-inflammatory drug Celebrex reduces formation of precancerous polyps that can lead to colorectal cancer. The drug’s cardiovascular risk complicates its general use as a preventive agent.
“Maybe it’s not for use in average-risk people,” Levin says, “but for those at higher risk of developing colon cancer, it might offer some help.” Celebrex is currently approved for individuals with familial adenomatous polyposis, who are at the highest risk.
M. D Anderson also played a major role in a breast cancer chemoprevention trial. Results from the Study of Tamoxifen and Raloxifene showed that both drugs reduce breast cancer risk by 50% for postmenopausal women considered at increased risk.
Raloxifene, an osteoporosis drug, had fewer side effects and also didn’t have the risk of uterine cancers seen with tamoxifen, notes Therese Bevers, M.D., associate professor in the Department of Clinical Cancer Prevention and principal investigator on the STAR trial at M. D. Anderson.
Participants in the trial have received information about which drug they were taking. Women assigned to raloxifene will continue to be provided with the drug until they have completed five years of treatment, according to Bevers. Those women assigned to tamoxifen can choose to continue taking the drug or switch to raloxifene to complete their treatment.