PARP Inhibitors for BRCA-Positive Breast Cancer
PARP inhibitors are targeted therapies used to treat people who were born with a mutation, or change, on the BRCA genes, and who have certain types of cancer. In breast cancer, they’re used to treat metastatic disease that is either hormone receptor-positive and HER2-negative, or triple-negative.
At the beginning of this century, researchers began creating clinical trials looking at PARP inhibitors as treatment for breast and other cancers. The U.S. Food and Drug Administration approved a PARP inhibitor to treat ovarian cancer in 2014 and has approved more PARP inhibitors to treat ovarian cancer since then.
In 2018 the FDA approved the first two PARP inhibitors for metastatic breast cancers caused by a BRCA gene mutation. They are olaparib (Lynparza), the first to be approved, and talazoparib (Talzenna). Researchers are studying other PARP inhibitors in clinical trials.
Mutations on the BRCA1 or BRCA2 genes make it harder for cells to repair DNA mistakes that happen when cells divide. This can significantly increase your risk of getting breast cancer. Once diagnosed with breast cancer, people with BRCA mutations may respond to treatment differently than people without these mutations.
PARP inhibitors stop an enzyme in the body, known as poly (ADP-ribose) polymerase, or PARP, from repairing cancer cell DNA. Cancer cells in people with BRCA mutations already have a hard time repairing themselves. PARP inhibitors make it even harder, and can cause the cancer cells to die.
- were born with a BRCA1 or BRCA2 mutation
- have metastatic breast cancer that is either hormone receptor-positive and HER2-negative, or triple-negative
- Have been treated with chemotherapy before, either for early-stage or metastatic breast cancer
Other PARP inhibitors, including niraparib, rucaparib and veliparib, have not yet been FDA approved for breast cancer. They may be available through clinical trials, most of which are for people with metastatic breast cancer. To find out if you’re eligible for a PARP inhibitor clinical trial, visit ClinicalTrials.gov and talk to your doctor.
The only way to know if you were born with a BRCA mutation is to get genetic testing. This testing is done using a blood, saliva or cheek-swab test. Some clinical trials are looking at somatic BRCA mutations. Somatic BRCA mutations develop in the DNA of the cancer, not in the DNA you were born with. Genomic testing is needed to learn if you have a somatic BRCA mutation. Genomic testing can’t be done on blood or saliva. It is done on an existing tumor sample, or your doctor may perform a new biopsy to get a new sample. If you are interested in genetic testing or genomic testing, talk to your doctor.
Olaparib and talazoparib are pills, as are most PARP inhibitors in clinical trials. Olaparib is usually taken twice every day, at least 12 hours apart, with or without food. Talazoparib is taken once each day, also with or without food. How often and at what dose you take a PARP inhibitor as part of a clinical trial, and whether you get it along with other anti-cancer medicines, will depend on the design of the study.
In general, PARP inhibitors cause fewer and less serious side effects than some other cancer treatments.
The most common side effects of PARP inhibitors are
They can also cause low red blood cell counts, called anemia, which can lead to fatigue and other problems; and low white blood cell counts, called neutropenia, which can increase your risk of infection. Your doctor will check your blood counts through blood tests before you start taking a PARP inhibitor and throughout your treatment to check for any changes. Sometimes, low blood cell counts can be a sign of a problem with your bone marrow, a fatty tissue found inside the bones. Bone marrow problems are not common but when they do happen, they can be serious.
Other serious but less common side effects of PARP inhibitors are problems with the lungs. If you have any shortness of breath, coughing or wheezing, or get a fever, tell your doctor right away so he or she can keep an eye on the problem.
Tell your doctor about any side effect you have, even when it seems mild. Your doctor may be able to give you medicine to treat the side effect or suggest lifestyle changes that could help manage it. If side effects are serious or impact your everyday life, your doctor may lower your dose, recommend a treatment break or switch you to a different medicine.