Drug Shows Early Promise for Hereditary Breast, Ovarian Cancers

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In two small clinical trials, the experimental agent Olaparib has shown early promise in the treatment of inherited breast and ovarian cancers. The findings, recently published in Lancet, represent the first therapy to target the deleterious hereditary mutations BRCA1 and BRCA2.
Olaparib, is a PARP inhibitor, a class of drugs of growing interest in cancer research. The drug, an oral agent, specifically targets cancers caused by faulty BRCA1 or BRCA2 genes. Both parp enzymes and proteins produced by the BRCA genes are involved in the repair of DNA.
Approximately 5% to 10% of all cancers are inherited. About 10% of women with ovarian cancer and 5% of women with breast cancer have a BRCA1 or BRCA2 mutation. Those with the genetic predisposition have a far higher chance of developing cancer in their lifetime, and at an earlier age.
"Women with a BRCA mutation and their family members who may also be at risk have a unique set of medical needs. Currently, we are able to offer cancer risk management to healthy women with BRCA mutations -- ranging from screening to preventative surgeries -- so that they can make personal decisions, in terms of their individualized cancer risk," says Banu Arun, M.D., associate professor in the Department of Breast Medical Oncology at MD Anderson. "Yet, we now know that BRCA cancers might behave differently than those without the mutation. Given this understanding, our ultimate goal is to be able to provide personalized treatment strategies to women with a BRCA-related cancer."
MD Anderson enrolled patients in both of the international multi-center studies. The trials were similar in design -- both compared dosage levels of Olaparib in women previously treated for their disease. The results were impressive: the objective response rates in women taking the higher dose in the ovarian and breast cancer studies was 41% and 33%, respectively. The drug was well tolerated with women experiencing few side effects.

"These findings, while early, may represent a paradigm shift in how we approach breast and ovarian cancer patients with BRCA mutations," says Karen Lu, M.D, professor in the Department of Gynecologic Oncology. "In addition to offering counseling and screening that are of benefit to the sisters, daughters and other female members of the patient's family, one day we may be able offer women with BRCA positive breast and/or ovarian cancers a therapy specifically targeted at their mutation."
Follow-up clinical trials in both diseases are ongoing. In the lab, Arun is investigating the role of parp inhibition in hormone positive disease and in combination with other chemotherapy agents.



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