Results from a small, very early study suggest that an experimental targeted therapy medicine called MK-4827 may have benefits for people diagnosed with a variety of advanced-stage cancers (including breast cancer) that have stopped responding to standard treatments. The results were presented at the 2010 Symposium on Molecular Targets and Cancer Therapeutics.
MK-4827 is a PARP inhibitor targeted therapy medicine. Other small, early studies have shown that some advanced-stage breast cancers that have stopped responding to standard treatments will respond to one of several other PARP inhibitors combined with standard chemotherapy.
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. This would make the cancer more susceptible to chemotherapy and make it harder for cancer to become resistant to chemotherapy.
In this study, 59 people diagnosed with a variety of advanced-stage cancers (including breast, lung, prostate, and ovarian) that didn't respond or had stopped responding to standard treatments were given MK-4827. MK-4827 is a pill taken by mouth once a day.
- 10 cancers (17%) had a partial response (showed signs of being weakened) to MK-4827
- Four cancers (7%) remained stable for some time while being treated with MK-4827
Though many of the cancers in this study were not breast cancer, most of the people in the study had a mutation in the BRCA1 or BRCA2 gene. Most inherited cases of breast cancer are associated with mutations in two genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two). Women with a BRCA1 or BRCA2 mutation have up to a 72% risk of developing breast cancer by age 80. Their risk of ovarian cancer also is higher than average. Abnormal breast cancer genes also have been linked to a higher risk of other cancers. Cells with an abnormal BRCA gene are unable to repair a specific type of DNA damage. Because of the way PARP inhibitors work, they may be uniquely suited to treat cancers in people with a BRCA genetic mutation. Of the 10 people who had a partial response to MK-4827 treatment, eight of them (80%) had an abnormal BRCA gene.
This was a phase I study. Phase I studies are done to help researchers figure out the best dose of a new treatment that can be used safely without serious side effects. Results from a phase I study also can help researchers figure out if a larger study involving more people makes sense. Based on promising results from this and other studies, doctors are continuing to study how PARP inhibitors can treat breast and other cancers.
If you're being treated for advanced-stage breast cancer that has stopped responding to standard treatments, you and your doctor may be considering a number of treatment options. If you're willing to participate in a clinical trial, you may have even more options available, possibly including an experimental PARP inhibitor such MK-4827. You can ask 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.
Editor’s Note: This article was updated on Jan. 22, 2019, with updated information on cancer risks associated with BRCA mutations.