Olaparib May Help Treat Triple-Negative Breast Cancer

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Results from two small, early studies suggest that adding the experimental targeted therapy olaparib to a taxane chemotherapy such as Taxol (chemical name: paclitaxel) or Abraxane (chemical name: albumin-bound or nab-paclitaxel) may be effective against triple-negative breast cancer. These results were presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting.

Triple-negative breast cancer is cancer that is estrogen-receptor-negative, progesterone-receptor-negative, and HER2-negative. Triple-negative breast cancers tend to be aggressive and difficult to treat.

DNA carries genetic information in both healthy and cancer cells. Chemotherapy medicines such as Taxol and Abraxane treat cancer by damaging its DNA or blocking DNA reproduction. But all cells can fix DNA damage caused by chemotherapy medicines. So sometimes cancer cells may not respond or stop responding to Taxol or Abraxane. When cancer stops responding to a treatment, it's called "treatment resistance."

Olaparib is a PARP inhibitor. The PARP (poly ADP-ribose polymerase) enzyme fixes DNA damage in cells, including DNA damage caused by chemotherapy medicines. Scientists developed PARP inhibitors based on the idea that a medicine that interferes with or inhibits the PARP enzyme might make it harder for cancer cells to fix damaged DNA, which would make the cancer more susceptible to chemotherapy and make it harder for cancer to become resistant to chemotherapy.

All these studies were very small and very preliminary.

In the first study, nine women diagnosed with advanced-stage, triple-negative breast cancer were treated with a combination of olaparib and Taxol. Three of the women had some response to the treatment. Still, four of the nine women developed a low white blood cell count (neutropenia), which can be a serious side effect of both Taxol and olaparib. White blood cells are part of the immune system and help fight infection.

In the second study, 10 women diagnosed with advanced-stage, triple-negative breast cancer were treated with a combination of olaparib and Taxol along with a granulocyte colony stimulating factor, a medicine that helps keep white blood cell counts normal during treatment. The women were given a granulocyte colony stimulating factor because so many women developed neutropenia in the first study. Neupogen (chemical name: filgrastim) and Neulasta (chemical name: pegfilgrastim) are both granulocyte colony stimulating factor medicines.

Four of the 10 women in the second study had some response to the treatment. Two women developed neutropenia even though they received a granulocyte colony stimulating factor medicine.

Because women in both studies developed neutropenia, the researchers used a Taxol dose that was lower than they wanted to use.

In the third study, olaparib was used alone to treat women diagnosed with either ovarian cancer (64 women) or triple-negative breast cancer (24 women). Although 41% of the ovarian cancers had some response to olaparib alone, none of the breast cancers had any response to olaparib alone.

All three studies were phase I or II studies. Phase I and II studies help researchers figure out the best dose of a new treatment that can be used safely without serious side effects. They also help researchers figure out if a larger study involving more people makes sense. Based on these promising results, doctors are continuing to study the potential benefits of using olaparib and other PARP inhibitors to treat breast and other cancers.

If you're being treated for triple-negative breast cancer, you and your doctor may be considering a number of treatment options, especially if the cancer has stopped responding to standard treatments. If you're willing to participate in a clinical trial, you may have even more options available, possibly including an experimental PARP inhibitor such olaparib. Talk to your doctor about clinical trials that might be a good fit for you and your unique situation. Visit the Breastcancer.org Clinical Trials pages for more information.

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