New Drug Class Promising Against Breast Cancer with BRCA Mutations

The results from two small studies have indicated that higher doses of an experimental drug called olaparib shows promise for women with breast cancer who carry BRCA1 and BRCA2 gene mutations. According to the study, olaparib stopped the growth of tumors and shrunk them in more than 40 percent of the cases. Olaparib works by making cancer cells even more genetically unstable than they already are, making them too defective to survive.

The study focused on 54 women with advanced genetic breast cancer whose cancers had metastasized to other organs and who had run out of standard treatment options. Half of the women received a high dose of olaparib and half received a low dose. Of the 27 who got a high dose, 11 (41 percent) had tumor shrinkage, and 12 (44 percent) had no tumor growth for at least 23 weeks of the first 24 weeks of study. Of the 27 women on the lower dose, six had tumor shrinkage and 12 had stable disease.

Study coauthor Susan Domchek, director of Penn's Cancer Risk Evaluation Program, called it "an enormous response rate" considering that the women had received at least three prior chemotherapies.

Up to 5 percent of women with ovarian cancer and approximately 10 percent of women with ovarian cancer carry the BRCA1 and BRCA2 genes. Because women who test positive for this gene mutation have an 80 percent risk of developing breast cancer in their lifetimes, they often have precautionary mastectomies. Scientists pointed out that if further tests on olaparib prove successful, they could be used at an early stage to treat and/or prevent disease within affected families.

Olaparib, made by AstraZeneca, is a new class of drug called a PARP inhibitor (poly adenosine-disphosphate-ribose polymerase) specifically designed to treat BRCA-related cancers to be tested on patients. PARP inhibitors are still years away from being marketed, however, because larger and longer studies are necessary.

"It is important to remember this drug is at a very early stage of development," said Andrew Tutt, director of the Breakthrough Breast Cancer Research Unit at King's College London, who led the trial.

Excerpts and further information in The Philadelphia Inquirer.

Aug 20, 2010