New treatment holds promise for rare, aggressive breast cancer

October is breast cancer awareness month

HOUSTON -- (October 9, 2009) -- A new investigational treatment for breast cancer -- called PARP inhibitors -- holds promise for patients who suffer from triple negative breast cancer, a rare, aggressive form of the disease, said a breast cancer specialist at Baylor College of Medicine.

"This is the most exciting new therapy for triple negative breast cancer and has the potential to work in other types of breast cancer," said Dr. C. Kent Osborne, director of both the NCI-designated Dan L. Duncan Cancer Center and Lester and Sue Smith Breast Center at BCM. "Until now, we have only had chemotherapy available as a treatment for these patients."

PARP hypothesis

PARP is an enzyme involved in DNA repair, Osborne said. DNA repair helps the body restore damage caused by genetic mutations that often lead to cancer.

"When there is a defect in one of the DNA repair pathways, our bodies cannot repair damage and mutations develop," said Osborne.

Patients who have mutations in the BRCA1 gene (a common mutation in patients with hereditary breast cancer) are predisposed to DNA damage. Some patients with triple negative breast cancers have tumors similar to BRCA1 – mutant tumors and also have a defect in DNA repair.

PARP inhibitors take advantage of this weakness or inability to repair DNA properly, Osborne said.

"The hypothesis is that if a cancer cell has a defect in one of the four or five DNA repair pathways and if we block one of the other gene pathways, it would be so overwhelming to the cancer cell that it would die," said Osborne. "Previous studies in cell cultures have shown that cancer cells with a defect in one DNA repair pathway die when treated with a PARP inhibitor that blocks a second pathway while normal cells survive."

Survival rates increased

In early human trials involving patients with this subtype, Osborne said, PARP inhibitors had outstanding results. The patients had cancer that spread to other parts of the body and did not respond to multiple other treatments.

"When PARP inhibitors were used in combination with chemotherapy, patients had a doubling in survival rates. Average survival was five months with chemo alone," said Osborne. "With PARP inhibitors and chemotherapy, average survival was nine months. This is a dramatic result when you consider that the patients in the study had tumors that were resistant to all available drugs."

Future studies will focus on using PARP inhibitors in early breast cancer patients.

Targeting pathways

Triple negative breast cancer accounts for 15 percent of all breast cancer cases that occur each year. These patients have tumors that are neither progesterone-receptor positive, estrogen-receptor positive nor HER-2 positive.

The Smith Breast Center received a grant last year to study the DNA of triple negative tumors to identify the proteins that stimulate tumor growth.

"We really do not know the genetic pathways that are causing this kind of cancer to grow and develop," said Osborne. "To develop new treatments that target these pathways, we need a greater understanding of the genetic makeup of these tumors."

Researchers with the Smith Breast Center are trying to develop a gene signature in a tumor sample that would tell which triple negative tumors have defective DNA repair and would likely respond to PARP inhibitors and specific types of chemotherapy, Osborne said.

For more information about clinical trials with PARP inhibitors, visit http://clinicaltrials.gov/.