PARP inhibitors for BRCA-positive breast cancer

PARP inhibitors are targeted therapies used to treat certain breast, ovarian, pancreatic, and prostate cancers. In breast cancer, PARP inhibitors are FDA approved for people who were born with a mutation, or change, on the BRCA genes. The breast cancer can be early-stage or metastatic 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 Administration first approved a PARP inhibitor to treat ovarian cancer 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 inherited BRCA gene mutation. They are olaparib (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 clinical trials.

How PARP inhibitors work

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 inherited 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 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 PARP inhibitors approved to treat breast cancer, olaparib and talazoparib. Talazoparib is only used to treat metastatic breast cancer, and olaparib is FDA approved for both high-risk early-stage breast cancer and metastatic disease. These medicines may be an option if you

• were born with a BRCA1 or BRCA2 mutation
• have 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 or talk with your doctor.

The only way to know if you were born with a BRCA mutation is to get genetic testing for an inherited 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 somatic 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. Tumor 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 biopsy 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

Olaparib and talazoparib are pills, as are most PARP inhibitors being studied 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. If you receive a PARP inhibitor through a clinical trial, the dose 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, PARP inhibitors cause fewer and less serious side effects than some other cancer treatments.

The most common side effects of PARP inhibitors are:

• nausea and vomiting
• fatigue
• lung and airway infection or inflammation
• diarrhea
• headache

They can also cause low red or white blood cell counts. Low red blood cell counts, called anemia, can lead to fatigue and other problems. Low white blood cell counts, called neutropenia, 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 look 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.

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 effect you notice, 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.