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New Type of Targeted Therapy May Help Treat Triple-Negative Disease

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Two studies found that experimental targeted therapy medicines -- called PARP inhibitors -- may make chemotherapy work better against aggressive forms of breast cancer. PARP inhibitors also may be able to treat breast cancer alone, without chemotherapy. The results were presented at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting.

DNA is the carrier of genetic information in both healthy cells and cancer cells. Chemotherapy medicines work against cancer by damaging DNA or blocking DNA reproduction. But both healthy cells and cancer cells can fix DNA damage caused by chemotherapy medicines. So sometimes cancer cells may not respond or stop responding to a particular chemotherapy medicine. When cancer stops responding to treatment, doctors call it "treatment resistance."

The poly ADP-ribose polymerase (PARP) enzyme fixes DNA damage in cells, including DNA damage caused by chemotherapy medicines. Researchers theorized that a medicine that interferes with (inhibits) the PARP enzyme might make it harder for cancer cells to fix damaged DNA, which would make it harder for the cancer to become resistant to chemotherapy.

A U.S. study looked at how well the PARP inhibitor BSI-201 worked in women diagnosed with metastatic triple-negative breast cancer. Triple-negative breast cancer is estrogen-receptor-negative, progesterone-receptor-negative, and HER2-negative. About 15% breast cancer cases are triple-negative. Triple-negative breast cancer is generally more aggressive, harder to treat, and has a worse prognosis than breast cancers that are not triple-negative.

About half of the 116 women in the BSI-201 study got a combination of two standard chemotherapy medicines. The other half of the women received BSI-201 in addition to the two standard chemotherapy medicines.

The women who got BSI-201 plus chemotherapy:

  • Were more likely to respond to treatment. About 48% of women who got BSI-201 had some type of response to treatment, compared to only 16% of women who didn't get BSI-201.
  • Lived longer without the cancer getting worse. Women who got BSI-201 lived for nearly 7 months without the cancer getting worse. Women who didn't get BSI-201 lived for a little more than 3 months without the cancer getting worse.
  • Lived longer overall. Women who got BSI-201 lived for nearly 9.2 months; women who didn't get BSI-201 lived for a little more than 3 months.

A British study looked at two doses of another PARP inhibitor -- olaparib -- in 54 women with an abnormal BRCA1 or BRCA2 gene diagnosed with breast cancer. Olaparib is a pill taken by mouth. The women received olaparib alone, without chemotherapy. This study didn't compare the women who got olaparib to a similar group of women who didn't get olaparib. So the results of this British study are considered preliminary. Still, the results are promising. About 40% of the women got benefits from a higher dose of olaparib and 22% of the women got benefits from a lower dose of olaparib.

Because something already is going wrong in cancer cells (which makes them cancerous), they are more likely to develop DNA damage on their own, even without chemotherapy. So it's possible that olaparib could work by itself, without chemotherapy, making some cancer cells more likely to be killed by their own DNA damage.

These research studies, though promising, were very small, very early studies. More research is needed before doctors completely understand how and when to use PARP inhibitors to treat breast cancer.

If you're being treated for an aggressive form of breast cancer, such as triple-negative breast cancer or cancer associated with an abnormal BRCA1 or BRCA2 gene, you and your doctor may be considering a number of treatment options. Especially if the cancer has stopped responding to standard treatments. You may have other options available, possibly including a PARP inhibitor, if you're willing to participate in a clinical trial. Ask your doctor if there are any clinical trials that might be a good fit for you and your unique situation. Visit the Clinical Trials section for more information.

Stay tuned to Research News to learn about the latest research on new, better ways to more effectively treat breast cancer.

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