New Drugs for Hard-to-Treat Breast Cancer

Study Shows PARP Inhibitors Fight Triple-Negative Breast Cancer

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June 2, 2009 (Orlando, Fla.) -- An experimental class of drugs may have potential for the treatment of two types of breast cancer that are notoriously difficult to treat.

Called PARP inhibitors, the drugs block the ability of damaged cells to repair themselves, causing cancer cells to die off or become more susceptible to chemotherapy drugs.

One PARP inhibitor, dubbed BSI-201, improved survival by 60% when added to standard chemotherapy drugs in women with so-called triple-negative breast cancer. Such tumors are hard to treat because they lack receptors for the hormones estrogen and progesterone as well as the protein HER2, which are targeted by current therapies.

The other PARP inhibitor, known as olaparib, shrank tumors in nearly half of women with cancer caused by mutations in the BRCA1 and BRCA2 genes. These inherited breast tumors often strike young women and are particularly aggressive.

"While preliminary, these are some of most exciting results we've seen in a long time," says Eric P. Winer, MD, director of the breast oncology center at the Dana-Farber Cancer Institute.

Winer, who wasn't involved with the work, moderated a news conference to discuss the findings at the annual meeting of the American Society of Clinical Oncology.

How PARP Inhibitors Work

PARP is short for poly (ADP-ribose) polymerase, an enzyme used by cancer cells to repair DNA damage.

All cells, cancerous and healthy alike, have multiple systems for DNA repair. Even if one pathway is turned off, most cells can survive.

Researchers are using PARP inhibitors to target tumors where one pathway is already shut down due to damage caused by genetic mutations or chemotherapy. Women with BRCA1/BRCA2 mutations lose a form of DNA repair and thus rely more heavily on the PARP pathway. Chemotherapy drugs damage the ability of cancer cells to repair DNA damage.

By blocking PARP in the already compromised tumor cells, the PARP inhibitors push the cells over the edge.

"There's DNA catastrophe, and tumors shrink," says Andrew Tutt, MD, PhD, director of the Breakthrough Breast Cancer Research Unit at Kings College in London and head of the olaparib study.


The first study involved 116 women with triple-negative breast cancer whose disease had spread to other parts of the body. These women, who account for 15% to 20% of breast cancer patients, have a very aggressive form of the disease for which chemotherapy is the only available therapy, says researcher Joyce O'Shaughnessy, MD, co-director of the Breast Cancer Research Program at Baylor-Charles A. Sammons Cancer Center in Dallas.

The women were randomly assigned to receive standard chemotherapy plus BSI-201, or standard chemo alone.

Women who received BSI-201 lived a median of 9.2 months, compared with 5.7 months for the chemotherapy-only group. Tumors shrank in 48% of patients treated with the PARP inhibitor, compared with 16% of patients on chemotherapy alone.

The new drug was well tolerated, with minimal side effects.

BiPar Sciences Inc., which makes the drug and funded the work, plans to launch a larger study this summer.

In the second study, 54 women with breast cancer that was deficient in BRCA1 or BRCA2 and that persisted despite several rounds of standard chemotherapy were given one of two doses of olaparib. Olaparib is given in pill form, while BSI-201 is injected.

Tumors shrank in 41% of those given the higher dose. The most common side effects were low-grade fatigue and nausea.

Drugmaker AstraZeneca, which funded the work, is in the process of designing a larger study, according to a company spokesperson.

More research is needed, all agree. But if the positive results hold up in future studies, PARP inhibitors will "be a real advance" for women with aggressive, hard-to-treat breast tumors, Winer says.

WebMD Health News Reviewed by Louise Chang, MD on June 02, 2009



American Society of Clinical Oncology Annual Meeting 2009, Orlando, Fla., May 29-June 2, 2009.

Eric P. Winer, MD, director, breast oncology center, Dana-Farber Cancer Institute, Boston.

Andrew Tutt, MD, PhD, director, Breakthrough Breast Cancer Research Unit, Kings College, London.

Joyce O'Shaughnessy, MD, co-director, Breast Cancer Research Program, Baylor-Charles A. Sammons Cancer Center, Dallas.

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