PARP Inhibitors for BRCA-Positive Breast Cancer

PARPinfo-icon inhibitors are targeted therapies used to treat people who were born with a mutationinfo-icon, or change, on the BRCA genes, and who have certain types of cancer. In breast cancer, they’re used to treat metastaticinfo-icon disease that is either hormone receptorinfo-icon-positive and HER2-negative, or triple-negative.

At the beginning of this century, researchers began creating clinicalinfo-icon trials looking at PARP inhibitors as treatment for breast and other cancers. The U.S. Food and Drug Administrationinfo-icon approved a PARP inhibitorinfo-icon to treat ovarian cancerinfo-icon in 2014 and has approved more PARP inhibitors to treat ovarian cancer since then.

In 2018 the FDAinfo-icon approved the first two PARP inhibitors for metastatic breast cancers caused by a BRCA geneinfo-icon mutation. They are olaparibinfo-icon (Lynparza), the first to be approved, and talazoparib (Talzenna). Researchers are studying other PARP inhibitors in clinical trials.

How PARP Inhibitors Work

Mutations on the BRCA1info-icon or BRCA2info-icon 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.

PARPinfo-icon inhibitors stop an enzyme in the body, known as poly (ADP-ribose) polymerase, or PARP, from repairing cancer cellinfo-icon 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.

Who Gets PARP Inhibitors

There are two PARPinfo-icon inhibitors approved to treat breast cancer, olaparib and talazoparib. These medicines may be an option if you

Other PARP inhibitors, including niraparib, rucaparib and veliparib, have not yet been FDAinfo-icon approved for breast cancer. They may be available through clinicalinfo-icon trials, most of which are for people with metastatic breast cancer. To find out if you’re eligible for a PARP inhibitorinfo-icon clinical trialinfo-icon, visit 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 somaticinfo-icon 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 tumorinfo-icon sample, or your doctor may perform a new biopsyinfo-icon to get a new sample. If you are interested in genetic testinginfo-icon or genomic testing, talk to your doctor.

How PARP Inhibitors Are Given

Olaparib and talazoparib are pills, as are most PARPinfo-icon inhibitors in clinicalinfo-icon trials. Olaparibinfo-icon 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 doseinfo-icon you take a PARP inhibitorinfo-icon as part of a clinical trialinfo-icon, and whether you get it along with other anti-cancer medicines, will depend on the design of the study.

PARP Inhibitor Side Effects

In general, PARPinfo-icon 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 cellinfo-icon counts, called anemia, which can lead to fatigueinfo-icon and other problems; and low white blood cellinfo-icon 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 inhibitorinfo-icon 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 tissueinfo-icon 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 effectinfo-icon you have, even when it seems mild. Your doctor may be able to give you medicineinfo-icon 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 doseinfo-icon, recommend a treatment break or switch you to a different medicine.

October 31, 2018
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