PARP Inhibitors: Exciting Option for Gene-Related Breast Cancer

Medically Reviewed by Brunilda Nazario, MD on August 30, 2021

By Jennifer K. Litton, MD, as told to Susan Bernstein

What are the latest treatment options for women with HER2-negative breast cancers and a mutation in their BRCA gene? New drugs called PARP (polymerase) inhibitors have shown success in targeting and treating these tumors.

The latest research shows that a new PARP inhibitor called talazoparib (Talzenna) can shrink breast tumors in patients before they start chemotherapy, and it has tolerable side effects like fatigue and hair loss. This once-daily pill is a promising way for women with metastatic breast cancer to get effective, highly targeted treatment.

Talazoparib is a pill you take once a day. When tested in patients with metastatic breast cancer, it has been shown to be more effective than standard chemotherapy.

When something works well in the metastatic setting, and works quickly, we often want to find out if we can move it into the earlier stages of cancer, to see if it can benefit women with earlier stages of breast cancer as well. We may look to see if it is more effective and/or less toxic.

This trial was built on an earlier trial’s results. We started with patients who had breast cancer and a known, inherited BRCA mutation, or change to a gene. We know patients with these mutations are very responsive to PARP inhibitors. We started by treating patients prior to their chemotherapy with this once-daily pill for 2 months prior to starting chemotherapy. What we found was that with just 2 months of treatment, the median tumor shrinkage in 13 patients was 88%.

Then, we moved into another study based on that result. We treated patients at the University of Texas MD Anderson Cancer Center with the talazoparib pill for 6 months prior to surgery. They did not get chemotherapy prior to the surgery. At surgery, we had 19 evaluable patients, and 53% had no invasive tumor identified during the surgery, or pathologic complete response (pCR).

Next, we started a larger, multicenter trial to see if the results were reproducible at other sites. While overall, the results were similar to what we found at MD Anderson, it was still a very small study, so it didn’t meet the predefined statistical significance threshold.

I think this study shows a pathway for the potential targeting of a very defined subset of breast cancer and perhaps other types of cancer. We often are adding more treatments to regimens for patients with cancer, and we’re trying to find new ways to treat them. In cancer research, and for all of our patients, we need to find what we can do to push the needle forward and save more patients’ lives. We also need to see what more we can do to spare them the toxicity and high cost of treatment. These factors are all very important for the future of cancer care.

PARP inhibitors target and block a specific pathway of the DNA damage repair. Patients with a BRCA mutation already have an impairment in their DNA damage repair mechanism. PARP inhibitors can block a different DNA repair mechanism. By blocking both in a BRCA-mutated cancer cell, we can impair its ability to divide and spread. Cancer researchers are committed to trying to build on all of these findings.

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Photo Credit: DavidBGray / Getty Images


Jennifer K. Litton, MD, vice president, clinical research, University of Texas MD Anderson Cancer Center.

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