Study: BRCA mutations may improve pembrolizumab response in early TNBC
The BRCAPATH study looked at people with early-stage triple-negative breast cancer (TNBC). Participants received chemotherapy alone or chemotherapy plus the immunotherapy drug Keytruda (pembrolizumab) before surgery. People with a BRCA mutation, particularly those with a BRCA1 mutation, were more likely to have no sign of invasive cancer at the time of surgery than participants without a mutation. The results suggest that among people with early-stage TNBC, those with BRCA mutations are likely to respond well to this treatment.
By: Piri Welcsh, PhD
Reviewed by: Allison Kurian, MD, MSc
RELEVANCE
Most relevant for: People who have an inherited mutation in BRCA1 or BRCA2 and have been diagnosed with TNBC.
Relevance: Medium-High
Strength of Science: Medium
Research Timeline: Post Approval
What is this study about?
The BRCAPATH study looked at outcomes for people with TNBC who received chemotherapy with the drug Keytruda or chemotherapy alone before having surgery to remove their cancer.
Keytruda is an drug that helps the immune system recognize and attack cancer cells. The researchers wanted to know whether people with or mutations are more or less likely to respond to adding Keytruda to their treatment before surgery.
Why is this study important?
The Keynote 522 study showed that adding the drug Keytruda to chemotherapy improved outcomes for people with TNBC. You can read more about Keynote 522 in our XRAY review here.
Keytruda received approval for treatment of breast cancer based on the results of the Keynote 522 study.
Many people with are also eligible for genetic testing because inherited or mutations are more common in this cancer type than in some other breast cancers. However, the Keynote 522 study didn’t look specifically at outcomes for people with inherited mutations.
Knowing whether status is associated with treatment response could help researchers better understand which tumors are most sensitive to this treatment and improve treatment planning.
Study findings
BRCAPATH researchers looked at 288 people with early TNBC: 234 received chemotherapy plus Keytruda, and 54 received chemotherapy without Keytruda.
Researchers compared pathologic complete response to treatment, meaning a response where no invasive cancer was found in the breast or at the time of surgery:
- 35 people treated with Keytruda plus chemotherapy had an inherited or mutation.
- Almost 90% of mutation carriers had a pathologic complete response, nearly double the 52% response rate of non-carriers.
After adjusting for other factors, mutations remained associated with pathologic complete response. The association was strongest for people with mutations. There were too few people with mutations to draw firm conclusions specifically about .
The study did not find a statistically significant difference in overall survival between people with mutations and those without. Since the number of people with mutations was small, and the study looked back at people who had already received treatment, the authors concluded that the findings should be confirmed in larger studies.
What does this mean for me?
If you have early (), your healthcare team may recommend chemotherapy plus Keytruda before surgery. This study suggests that people with an inherited or mutation are likely to respond well to this treatment.
If you have and have not had genetic counseling or genetic testing, ask your doctor whether testing is recommended for you. test results may affect treatment choices for some people with breast cancer, including decisions about surgery, risk management and whether treatment, such as Lynparza (), is appropriate after chemotherapy and surgery.
If you have and test negative for a mutation, you may still benefit from Keytruda plus chemotherapy. The KEYNOTE-522 study found that this treatment improves response and survival for eligible people with high-risk, TNBC, regardless of their mutation status.
This study alone should not be used to decide whether Keytruda is right for you. Treatment decisions depend on many factors, including cancer , tumor features, other health conditions, side effects, personal preferences and current guidelines. Talk with your healthcare providers about the benefits and risks of Keytruda, genetic testing and other treatment options.
It is important to know that this study included a small number of participants and was based on data from people who had already been treated. More research is needed before status alone can guide Keytruda (pembrolizumab) treatment decisions.
Reference
Popescu BV, Simon L, Blaye C, et al. pathogenic variants and response in early patients treated with pembrolizumab: outcomes of the BRCAPATH study. Breast Cancer. Published online June 16, 2026. doi:10.1007/s12282-026-01878-9.
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 9/11/2026
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