Experimental Olaparib May Help Treat People With Abnormal BRCA1 or BRCA2 Gene

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A study found that two-thirds of people with an abnormal BRCA1 or BRCA2 gene being treated for advanced-stage breast, ovarian, or prostate cancer got some benefit from olaparib, an experimental targeted therapy medicine. People who didn't have an abnormal BRCA1 or BRCA2 gene didn't get any benefit from olaparib. Olaparib is a type of targeted therapy medicine called a PARP inhibitor.

Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two). Women with an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70. Their risk of ovarian cancer also is higher than average. Men with an abnormal BRCA gene have a higher risk of both breast and prostate cancer.

DNA carries genetic information in both healthy cells and cancer cells. Cells can develop DNA damage spontaneously or from exposure to specific things in the environment (too much sun, for example) that make DNA damage more likely to happen. But cells can detect and repair damage to DNA. When DNA is damaged in a healthy cell and the damage isn't fixed, that cell can become cancerous. Abnormal BRCA1 and BRCA2 genes are thought to increase the risk of breast and other cancers because these abnormal genes interfere with cells' ability to repair damaged DNA.

The poly ADP-ribose polymerase (PARP) enzyme fixes DNA damage in both healthy and cancer cells. Researchers believe that a medicine like olaparib, which interferes with (inhibits) the PARP enzyme, might make it even harder for cancer cells with an abnormal BRCA1 or BRCA2 gene to fix DNA damage. This would make it harder for the cancer cells to survive. In other words, a PARP inhibitor might make some cancer cells less likely to survive their DNA damage.

Research in the lab on cancer cells with an abnormal BRCA1 or BRCA2 gene showed that the cells were 1,000 times more sensitive to PARP inhibition than cancer cells that didn't have an abnormal BRCA gene. Based on those results, the researchers felt that treating cancers in people with an abnormal BRCA1 or BRCA2 gene would likely be effective.

In this study, 60 people diagnosed with advanced-stage cancer that had stopped responding to other treatments received olaparib, a pill taken by mouth. About a third of the people in the study (21 people) were known to have an abnormal BRCA1 or BRCA2 gene. One other person was thought to have an abnormal BRCA gene based on a strong family history.

The results:

  • Of the 19 people with an abnormal BRCA gene who were followed throughout the study, 12 (63%) got some benefit from olaparib; 2 people got benefits that lasted for a year or longer.
  • None of the people without an abnormal BRCA gene got any benefit from olaparib.
  • Most of the people who had treatment-related side effects had side effects that weren't severe; the risk of side effects was lowered by reducing the daily dose of olaparib.

Because these results were so encouraging, the researchers suggested that medical groups and government agencies reconsider how targeted therapy medicines are tested and approved. For example, when testing olaparib, the researchers looked at how it worked on a number of different types of cancer that all had an abnormal BRCA1 or BRCA2 gene, rather than looking at how the medicine worked in just one type of cancer.

Based on these results, the researchers think that olaparib could be a successful treatment for cancers with an abnormal BRCA1 or BRCA2 gene.

In this study olaparib was used alone. Other research has shown that giving another PARP inhibitor, BSI-201, plus chemotherapy to women diagnosed with advanced-stage, triple-negative breast cancer caused the cancers to respond better to chemotherapy compared to cancers treated with chemotherapy alone. Cancers treated with BSI-201 plus chemotherapy also were less likely to become resistant to chemotherapy. Some chemotherapy medicines work by causing DNA damage in cancer cells. Using a PARP inhibitor with these chemotherapy medicines might make it harder for cancer cells to fix damaged DNA, which makes it harder for the cancer to become resistant to chemotherapy.

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. If the cancer has stopped responding to standard treatments, other treatment options may include a PARP inhibitor such as olaparib 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 Breastcancer.org Clinical Trials pages for more information.

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