Drug slows tumour growth in some breast cancers
Published Tuesday, July 6, 2010 8:41AM EDT
TORONTO - An experimental drug designed to attack breast cancer cells caused by a particular genetic mutation appears to show some promise in arresting the growth of tumours, researchers say.
In a small study of women with advanced breast cancer caused by a mutation in the BRCA1 or BRCA2 gene, the oral drug olaparib was found to slow tumour growth to varying degrees in 85 per cent of patients, researchers report in Tuesday's edition of The Lancet.
"This is the first time that we have been able to take the genetic reason a person has developed cancer and make it a target," said study co-author Dr. Susan Domchek of the University of Pennsylvania School of Medicine.
"Most of the time we look at what is going on in the tumour itself and then figure out how to target it," Domchek, director of the Cancer Risk Evaluation Program at the university's Abramson Cancer Center, said in a release.
"But in this situation, the women all had an inherited mutation in either the BRCA1 or BRCA2 gene and we could exploit that weakness in the tumour. It is a strategy that may cause fewer side-effects for patients."
The drug did not cure the cancer, but prolonged the patients' lives for a some months.
Olaparib works by inhibiting a protein called PARP, or poly(ADP-ribose) polymerase. Both PARP and proteins made by the BRCA genes are involved in repairing DNA. Inhibiting PARP in cancer cells that already lack a BRCA gene causes them to die.
"If you put too much stress on the cancer cell, it can't take it and it falls apart," said Domchek, noting that the drug appears to have relatively little effect on non-cancerous cells.
Up to five per cent of women with breast cancer and about 10 per cent of women with ovarian cancer carry a mutation in the genes BRCA1 or BRCA2.
The study, which involved centres in the U.S., the U.K., Australia, Germany and Sweden, was designed to test the safety and efficacy of the drug in what's known as a Phase 2 trial. Researchers enrolled 54 women with advanced breast cancer that had not responded to conventional treatment, giving half of them 400 mg of olaparib twice daily and the other half each 100 mg twice a day.
The heftier dose appeared to work better: a higher percentage of women had tumour shrinkage or slowed tumour growth compared with the lower-dose group. And those on the higher dose survived slightly longer.
Dr. Stephen Chia, chair of the B.C. Cancer Agency's Breast Tumour Group, said the use of the drug "made really good sense."
"This is one of the first and largest studies so far where they are targeting what I call the Achilles heel of cancers," he said Monday from Vancouver.
While the drug didn't cure the women of their cancer, it did prolong their lives on average for several months, Chia said, and it offers hope that drugs indeed can be developed to specifically manipulate the inherent weaknesses of cancer cells.
For Dr. Steven Narod, director of the Familial Breast Cancer Research Unit at Women's College Hospital in Toronto, olaparib holds more promise as a preventive therapy.
"I think this has some benefit for treatment, but it's pretty skimpy," he said. "I really think and I'm excited at the possibility that this drug would be useful for prevention."
Narod said he hopes to study olaparib in a large group of women who carry the BRCA1 mutation.
"The reason I think prevention is the future on this is because ... the most chances of killing the cells is when the cancers are really small," he said. "If the cancer's tiny and microscopic, we think we have a shot at killing all the cells. If the cancer's large and present throughout the body, the chance of killing all the cells is remote."
Domchek said more clinical trials are needed before olaparib or other PARP-inhibitors in development will be ready for use in regular practice.