PARP inhibitors for BRCA-positive breast cancer

PARPinfo-icon inhibitors are targeted therapies used to treat certain breast, ovarianinfo-icon, pancreatic, and prostate cancers. In breast cancer, PARP inhibitors are FDAinfo-icon approved for people who were born with a mutationinfo-icon, or change, on the BRCA genes. The breast cancer can be early-stageinfo-icon or metastaticinfo-icon and must be HER2-negative.

Since the early 2000s, researchers have studied PARP inhibitors as treatments for breast and other cancers. The U.S. Food and Drug Administrationinfo-icon first approved a PARP inhibitorinfo-icon to treat ovarian cancerinfo-icon in 2014. Since then, it has approved more PARP inhibitors to treat ovarian and other cancers.

In 2018, the FDA approved the first two PARP inhibitors for metastatic breast cancers caused by an inheritedinfo-icon BRCA geneinfo-icon mutation. They are olaparibinfo-icon (Lynparza) and talazoparib (Talzenna). In March 2022, the FDA expanded the approval for olaparib to include high-risk early-stage breast cancers. Researchers continue to study these and other PARP inhibitors in clinicalinfo-icon trials.

“PARP inhibitors represent a new option those with inherited BRCA 1 or 2 mutations, and therefore expand the patient population who should have testing for BRCA mutations to include anyone with metastatic breast cancer or those with early-stage breast cancerinfo-icon who have positive nodes, or still have cancer left at the time of surgeryinfo-icon when they receive chemotherapyinfo-icon or hormonal therapyinfo-icon prior to surgery,” says Debu Tripathy, MD.  

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 inheritedinfo-icon 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 inherited 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, olaparibinfo-icon and talazoparib. Talazoparib is only used to treat metastaticinfo-icon breast cancer, and olaparib is FDAinfo-icon approved for both high-risk early-stage breast cancerinfo-icon and metastatic disease. These medicines may be an option if you

Other PARP inhibitors, including niraparib, rucaparib, and veliparib, have not yet been FDA 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 ClinicalTrials.gov or talk with your doctor.  

The only way to know if you were born with a BRCA mutation is to get genetic testinginfo-icon for an inheritedinfo-icon mutation. Genetic testing looks for inherited, or germline, BRCA mutations. This testing is done using a blood, saliva, or cheek-swab test.

Some clinical trials are looking at PARP inhibitors and other therapies for somaticinfo-icon BRCA mutations. Somatic BRCA mutations develop in the DNA of the cancer, not in the DNA you were born with. Somatic mutations are not inherited. Tumorinfo-icon biomarker or genomic testing is needed to learn if you have a somatic BRCA mutation. Tumor biomarker testing can’t be done on blood or saliva. It is done on an existing tumor sample, or your doctor may perform a new biopsyinfo-icon to get a new sample. If you are interested in genetic testing or tumor biomarker testing, talk with your doctor.

How PARP inhibitors are given

Olaparibinfo-icon and talazoparib are pills, as are most PARPinfo-icon inhibitors being studied in clinicalinfo-icon 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. If you receive a PARP inhibitorinfo-icon through a clinical trialinfo-icon, the doseinfo-icon you receive, when you take it, and whether you also take 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 or white blood cellinfo-icon counts. Low red blood cellinfo-icon counts, called anemiainfo-icon, can lead to fatigue and other problems. Low white blood cell counts, called neutropeniainfo-icon, 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 look 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.

Lung problems are less common but can be serious side effects of PARP inhibitors. If you have any shortness of breath, coughing or wheezing, or develop a fever, tell your doctor right away so they can keep an eye on the problem.

Tell your doctor about any side effectinfo-icon you notice, 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.

Updated 
May 22, 2022
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