IDENTIFYING THE RISK FACTOR
The urgent need to prevent the return of breast cancer among survivors of the disease is the focus of research by Dr. Sambasivarao Damaraju and his team at the Damaraju Cancer Genomics Laboratory at the University of Alberta in Edmonton.
Each year, 1.4-million patients worldwide are diagnosed with breast cancer. Among the survivors, 30% or more experience a recurrence of the disease. Identifying those individuals most likely to face a second diagnosis makes it possible to treat the disease more aggressively at an early stage and to prevent or significantly reduce the possibility of reappearance.
“A major breakthrough happened when we discovered [genetic] markers that help identify those who are at risk for recurrence,” says Damaraju, a faculty member in the medicine and dentistry department at the University of Alberta and a researcher at the Cross Cancer Institute in Edmonton.
He says his research, funded by the Canadian Breast Cancer Foundation, is focused on sporadic rather than hereditary breast cancer, meaning that no other family member has been previously diagnosed with the disease.
“The importance of my research is that 80% or more of total breast cancers diagnosed in the world belong to sporadic breast cancer. But there were no genetic markers for sporadic breast cancer until very recently,” he explains.
Identifying those at risk before the disease appears, he says, in principle provides opportunities to screen and offer them preventive therapies.
As well as focusing on understanding why sporadic cancer occurs, the types of genes or gene regions involved and discussing risk, “we should also talk about those genes or markers that afford protection against sporadic breast cancer,” says Damaraju, a founding director of the CBCF Tumor Bank, which provides specimens for this type of research to specialists in Canada and around the world. The knowledge gained from understanding risk and protection will help in the development of screening tools, predictors and eventually develop means of prevention.
Screening for the markers, he says, is based on isolating the DNA (deoxyribonucleic acid — the cellular blueprint) in the patient’s blood, noting that this is different from screening a tumour.
Using the DNA screen to identify those at high risk for a recurrent form of the disease is something that hasn’t been addressed in the literature, he says. “Through this kind of research, we have reported several potential markers. The benefit is that on the day that patients are diagnosed with breast cancer, we have the tools in place to say who among them are at high risk for recurrence.” Any treatments tailored for these patients could be more aggressive.
The immediacy is additionally effective because a recurrence five or 10 years down the road is frequently “in a more aggressive form and more difficult to treat,” he says.
In continuing the research, Damaraju and his team aim to pinpoint the genetic markers for the various types of breast cancer. “We know from our research that each sub-type of breast cancer has unique markers,” he says. He emphasizes that breast cancer is not one disease but “a bag of several sub-types, so we should not imagine that one drug will cure all types of breast cancer.”
Another area of research is to use genetic markers to determine the likelihood of adverse reactions to certain drugs.
“It is not sufficient to determine who might be at risk or whether the disease might come back,” he says. “To be able to administer aggressive therapies, it is also important to identify who might be at risk for adverse reactions to drugs as a consequence of such therapies and who can tolerate them. Then we can administer these drugs with a lot more confidence. If the dosage of a drug is lowered or discontinued halfway due to adverse reactions, the real benefit is not assured, and the individuals are still at risk for recurrence.”
In the first round of DNA testing, 369 Caucasian women diagnosed with sporadic (luminal A) breast cancer — a form with a good prognosis for treatment and recovery — were tested in Alberta. Of this group, 155 suffered a recurrence. Damaraju and his team are now studying a larger sample of 2,000 patients, which will give further analysis of predictors and genetic markers indicating the probability of disease recurrence.