Study: Treating triple-negative breast cancer in people with inherited BRCA1 or BRCA2 mutations

RELEVANCE

Most relevant for: People who have early-stage triple-negative breast cancer and an inherited mutation in BRCA1 or BRCA2.

Relevance: Medium-High

Strength of Science: High

Research Timeline: Human Research

More rating details

Dr. Erica Mayer from the Dana-Farber Cancer Institute presented findings from the TBCRC-056 study, which looked at Zejula (niraparib) and Jemperli (dostarlimab) for neoadjuvant treatment of people with early-stage (stages 1-3) triple-negative breast cancer (TNBC) who had an inherited mutation in BRCA1 or BRCA2. (Although the study also enrolled people with HER-2 negative disease and those with PALB2 mutations, Dr. Mayer only presented results from the triple-negative group, none of whom had PALB2 mutations).

Zejula is a PARP inhibitor, a type of targeted therapy. PARP inhibitors make it harder for certain cancer cells to fix their own DNA, and the cancer cells then die. Jemperli is a type of immunotherapy that helps the body's immune system find and destroy cancer cells more effectively.

Study participants and design

Participants had either a BRCA1 or BRCA2 mutation and TNBC that was stages 1-3. You can find more information on the stages and subtypes of breast cancer here.

64 participants were divided randomly into two groups:

• Group A received Zejula and Jemperli for 18 weeks before surgery. 
• Group B received Zejula alone for 3 weeks, then Zejula and Jemperli for 15 weeks before surgery.

Study findings

In both groups, 50% of participants had a pathologic complete response (pCR), meaning there were no detectable cancer cells at the time of surgery.

These results suggest that combining a targeted therapy with immunotherapy may help the body’s immune system better target and destroy cancer cells, potentially leading to improved outcomes for patients when used before surgery.

Side effects

Side effects experienced by the participants were as expected—a combination of the same side effects often seen when each drug is used separately.

• 82% of participants experienced side effects.
• Most common side effects:
  •  Anemia (low red blood cell counts): 26% of participants
  • Fatigue: 22% of participants

Dr. Nadine Tung from Harvard University discussed the OlympiaN trial, which tested how well the PARP inhibitor Lynparza (olaparib) alone or in combination with Imfinzi (durvalumab), an immunotherapy drug (a checkpoint inhibitor) in patients with inherited mutations in BRCA1 or BRCA2.

Lynparza prevents cancer cells from repairing their DNA, while Imfinzi helps the immune system find and attack cancer cells. Researchers wanted to know if combining these two drugs would improve outcomes for patients with an inherited BRCA1 or BRCA2 mutation and early-stage TNBC.

Study participants and findings

Participants included 50 people with early-stage, HER2-negative breast cancer, including TNBC. All participants had an inherited BRCA1 or BRCA2 mutation.

Participants were divided into two groups based on their tumor size and received 4-6 cycles of targeted therapy (each cycle lasting 28 days), followed by surgery.

• Group A, a lower-risk group with smaller tumors, received Lynparza alone.
  • 68% had no detectable cancer (a pathological complete response, pCR) after pre-surgery treatment.
• Group B, a higher-risk group with larger tumors, received Lynparza and Imfinzi for 18 weeks.
  • 80% had no detectable cancer (a pathological complete response, pCR) after pre-surgery treatment.

It is important to note that because participants had tumors of different sizes before treatment, the two groups cannot be directly compared to each other. Rather, the important takeaway is that patients in both groups had a positive response, whether they received Lynparza alone or Lynparza and Imfinzi before surgery.  The researchers suggest that these approaches might be an alternative to current pre-surgery chemotherapy.

Side effects

Side effects experienced by participants were as expected—a combination of the same side effects often seen when each drug is used separately.

• All but one participant experienced side effects.
• The most commonly reported side effect was anemia (low red blood cell count): 12% of participants.

What does this mean for me?

Results from the two studies were highlighted during the 2025 San Antonio Breast Cancer Symposium. Both studies concluded that treatment before surgery with combination therapies, with or without immunotherapy, may improve outcomes for people with early-stage triple-negative breast cancer who have an inherited mutation in BRCA1 or BRCA2. Eventually, these promising combined therapies may be used as an alternative to pre-surgery chemotherapy for some patients. However, more research is needed to confirm the benefits and understand the risks of these treatment combinations. Though these treatments are not standard and available to all, they may be available through clinical trials.

Reference

Mayer EL, Graham N, Leon-Ferre RA, et al. Tbcrc 056: a phase 2 study of neoadjuvant niraparib with dostarlimab for patients with BRCA- or PALB2-mutated breast cancer: results from the TNBC cohorts. 2025 San Antonio Breast Cancer Symposium. Abstract RF5-02. Presented December 12, 2025.

Tung N, Stradella A, Brofsky A, et al. OlympiaN: a phase 2, multicenter, open-label study to assess the efficacy and safety of neoadjuvant olaparib monotherapy and olaparib plus durvalumab in patients with BRCA mutations and early-stage HER2-negative breast cancer. 2025 San Antonio Breast Cancer Symposium. Abstract RF5-03. Presented December 12, 2025.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 2/3/26