Triple-negative breast cancer is the subtype with the clearest proven benefit from checkpoint immunotherapy. Pembrolizumab can improve survival in eligible patients with high-risk early-stage TNBC and in certain patients with advanced TNBC whose tumors have a PD-L1 CPS of at least 10. For most hormone receptor-positive or HER2-positive breast cancers, checkpoint inhibitors are not routine treatment. Rare MSI-H, dMMR or TMB-H findings may provide a separate treatment option in advanced disease.[1]
| Subtype | Who may benefit |
|---|---|
| Triple-negative | Eligible high-risk early-stage patients, regardless of PD-L1 status; selected advanced cases with PD-L1 CPS ≥10. |
| Hormone receptor-positive, HER2-negative | Selected high-risk patients have shown improved pathological response in trials. This does not establish routine use for the whole subtype. |
| HER2-positive | HER2 positivity alone does not support checkpoint inhibitor treatment. HER2-targeted drugs remain central to care. |
| Any subtype with qualifying biomarkers | Some advanced MSI-H/dMMR or TMB-H tumors may qualify under a tumor-agnostic indication, subject to prior-treatment and testing requirements. |
The evidence below concerns immune checkpoint inhibitors. These drugs differ from NK-cell therapy; their survival results cannot be transferred to an NK-cell infusion.
Early-Stage Triple-Negative Breast Cancer
KEYNOTE-522 enrolled 1,174 patients with stage II–III TNBC. Patients received pembrolizumab plus chemotherapy before surgery, followed by pembrolizumab after surgery, or the corresponding chemotherapy-and-placebo regimen.
After a median follow-up of 75.1 months, estimated five-year overall survival was 86.6% versus 81.7%, an absolute difference of 4.9 percentage points. These are results for the complete treatment strategy, not pembrolizumab alone.[2]
- PD-L1 positivity is not required for this early-stage regimen.
- T1N0 tumors were not included. Patients with tumors no larger than 2 cm and no regional lymph node involvement cannot assume the same benefit.
- Treatment began before surgery. The trial does not establish the same benefit from starting pembrolizumab only after surgery.
The study included surgery and up to nine postoperative pembrolizumab doses, given every three weeks. A complete pathological response did not automatically cancel postoperative treatment; disappearance on a scan was not a reason to omit surgery.[3]
Advanced Triple-Negative Breast Cancer
KEYNOTE-355 enrolled 847 patients with inoperable locally recurrent or metastatic TNBC who had not received systemic treatment for advanced disease. In the PD-L1 CPS ≥10 subgroup, median overall survival was 23.0 months with pembrolizumab plus chemotherapy and 16.1 months with placebo plus chemotherapy.[4]
The 6.9-month difference is a comparison between groups, not a prediction for an individual. The trial does not establish the same survival benefit for CPS below 10.
A report stating only “PD-L1 positive” may be insufficient. The oncologist needs the test method, scoring system and numerical result. If a patient previously received pembrolizumab for early-stage cancer, retreatment also requires review of the recurrence interval, previous response and immune-related side effects.
Pembrolizumab Plus an ADC
On June 24, 2026, the FDA approved sacituzumab govitecan, an antibody-drug conjugate (ADC), with pembrolizumab for first-line treatment of adults with unresectable locally advanced or metastatic TNBC and PD-L1 CPS ≥10.
In ASCENT-04/KEYNOTE-D19, the combination produced a median progression-free survival of 11.2 months, compared with 7.8 months for chemotherapy plus pembrolizumab. Overall survival data were immature at the approval analysis. These figures measure time before progression or death, not the overall survival reported in KEYNOTE-355. Approval outside the United States must be checked locally.[5]
Hormone Receptor-Positive Breast Cancer
KEYNOTE-756 studied 1,278 patients with high-risk, early-stage, grade 3 ER-positive/HER2-negative cancer who met specific tumor and lymph node criteria. The 2025 analysis reported pathological complete response rates of 24.3% with pembrolizumab plus chemotherapy and 15.6% with placebo plus chemotherapy.
Event-free survival data were not mature in that analysis, so the response improvement alone does not establish longer survival. Both groups received endocrine therapy after surgery; pembrolizumab did not replace it.[6]
HER2-Positive Breast Cancer
HER2-positive disease is generally treated with HER2-targeted drugs as part of the regimen. Some of these drugs engage immune mechanisms, but that does not make them interchangeable with PD-1 or PD-L1 inhibitors.
HER2-low status is not an independent indication for checkpoint immunotherapy. It can affect eligibility for certain ADC treatments. A BRCA1/2 mutation likewise informs other decisions, including PARP inhibitor use, rather than automatically qualifying a patient for pembrolizumab.[7]
Biomarker-Based Exceptions
Some patients outside the usual TNBC treatment groups may qualify for pembrolizumab because their tumors are MSI-H/dMMR or TMB-H. Under the relevant US indications, requirements include unresectable or metastatic disease, progression after prior treatment and no satisfactory alternative options.
For TMB-H, the threshold is at least 10 mutations per megabase, measured with an FDA-approved test. Eligible patients may receive pembrolizumab alone. This threshold is specific to the relevant indication, not a universal rule for every immunotherapy drug or testing platform.[8]
Risks That Affect Treatment
In KEYNOTE-355, grade 3–5 treatment-related adverse events occurred in 68.1% of patients receiving pembrolizumab plus chemotherapy and 66.9% receiving placebo plus chemotherapy. These rates cover the entire regimen, not immune-related reactions alone.[9]
Checkpoint inhibitors can inflame the lungs, bowel or liver and damage hormone-producing glands. Some patients need long-term hormone replacement. Active autoimmune disease, an organ transplant or a previous serious immune reaction requires individual assessment. Reactions can also develop after treatment stops.[10]
Report persistent diarrhea, bloody stools, new breathlessness, yellow skin or eyes, or unusual thirst and frequent urination promptly. Severe breathing difficulty, chest pain, fainting or confusion requires immediate medical attention.