Breast Cancer Immunotherapy: Approved Treatments, Biomarkers and Emerging Research

Immunotherapy’s proven role in breast cancer is narrower than people often expect. Checkpoint inhibitors such as pembrolizumab have an established place in selected triple-negative breast cancer (TNBC), a subtype that does not respond to hormone-blocking or HER2-targeted drugs.

This guide covers where immunotherapy fits, what the research shows and what remains experimental. International patients can find more detail through Treatment in Germany.

Where Immunotherapy Fits in Breast Cancer Treatment

Breast cancer is not one disease. Tumors are tested for estrogen receptors (ER), progesterone receptors (PR) and HER2, and the results largely decide which drugs apply:

• Triple-negative breast cancer: tests negative for all three, so hormone therapy and HER2-targeted drugs are not an option; chemotherapy stays central to treatment, and checkpoint inhibitors have shown clear benefit in selected cases
• Other breast cancer types: hormone receptor-positive and HER2-positive cancers are being studied, but checkpoint inhibitors are not yet routine treatment

Checkpoint Inhibitors and the Immune System

The immune system has built-in brakes that stop it from attacking the body’s own cells. Some tumors take advantage of one of these brakes. Cancer cells, and immune cells around them, can carry a protein called PD-L1 that attaches to PD-1, a receptor on T cells, and switches those T cells off.

• Pembrolizumab: blocks PD-1, helping restore T-cell activity against cancer cells
• Chemotherapy: damages or kills rapidly dividing cells directly instead of activating the immune system
• Combination use: pembrolizumab is given together with chemotherapy or, in one newer metastatic regimen, with an antibody-drug conjugate (described below). In early-stage disease it then continues alone after surgery

The PD-L1 Test for Metastatic TNBC

For pembrolizumab-based treatment of metastatic TNBC, the tumor is tested for PD-L1, and the result is reported as a combined positive score, or CPS, a measure of PD-L1 on tumor cells and nearby immune cells.

• CPS 10 or higher: pembrolizumab-based treatment may be an option for metastatic TNBC
• CPS below 10: trial evidence has not shown the same survival benefit, so the treating team considers other first treatment options, which may include chemotherapy alone
• A higher CPS: raises the likelihood of benefit but does not guarantee a response

Immunotherapy for Early-Stage Triple-Negative Breast Cancer

For high-risk early-stage or locally advanced TNBC, pembrolizumab is generally given with chemotherapy before surgery, then continued alone afterward. This was tested in KEYNOTE-522, a phase 3 trial with a median follow-up of 7.8 years.

• Estimated seven-year overall survival (share of patients alive at seven years): 85.1% with pembrolizumab plus chemotherapy, versus 77.2% with chemotherapy alone
• PD-L1 status: the CPS test is not required for this early-stage use, because the benefit was seen regardless of status

Immunotherapy for Metastatic Triple-Negative Breast Cancer

For locally recurrent unresectable or metastatic TNBC, pembrolizumab combined with chemotherapy can be used as a first treatment in eligible patients.

• Eligibility: a CPS of 10 or higher, with no prior chemotherapy for metastatic disease
• KEYNOTE-355: in this CPS 10 or higher group, median overall survival was 23.0 months with pembrolizumab plus chemotherapy, versus 16.1 months with chemotherapy alone
• Sacituzumab govitecan with pembrolizumab: in August 2026, the European Commission authorized this combination as a first treatment for eligible patients with a CPS of 10 or higher who have not received prior systemic therapy for metastatic disease

Sacituzumab govitecan is an antibody-drug conjugate that delivers a chemotherapy drug to cells carrying the Trop-2 protein. In this regimen it replaces the chemotherapy partner, while pembrolizumab continues. This approval is based on a separate trial, ASCENT-04, so its results should not be compared directly with KEYNOTE-355.

A wider view of these options in Germany is available in this guide to immunotherapy for breast cancer in Germany.

Possible Side Effects of Checkpoint Inhibitor Treatment

Releasing the immune system’s brake can let it affect healthy tissue, not only the tumor. These reactions can appear during or months after treatment.

• Thyroid problemsare the most frequently reported hormone-related (endocrine) side effect and can become permanent, sometimes needing long-term hormone replacement
• Adrenal and pituitary gland problemsare less common but serious, and can also need ongoing hormone treatment
• Skin, bowel, liver and lung inflammationcan also occur and vary widely in severity

Many immune-related reactions can be managed when recognized early, often by pausing treatment and using corticosteroids or other organ-specific treatment. Some complications can be serious or permanent. People with an active autoimmune disease or an organ transplant need individual assessment before treatment.

When These Side Effects Need Medical Attention

Report any new or worsening symptom to the treating team promptly, even after treatment ends. Severe or rapidly worsening symptoms, especially breathing difficulty, need urgent assessment, not a routine appointment. Symptoms to watch for include:

• persistent diarrhea or abdominal pain
• new cough or breathlessness
• yellowing of the skin or eyes
• severe fatigue, dizziness or repeated vomiting
• a widespread or blistering rash
• severe headache or changes in vision

Newer and Investigational Approaches

• High-risk, estrogen receptor-positive, HER2-negative early breast cancer: in the KEYNOTE-756 trial, adding pembrolizumab to chemotherapy before surgery raised the pathological complete response rate, meaning no invasive cancer was found in the breast or lymph nodes removed at surgery, to 24.3% versus 15.6% with chemotherapy alone. This is an encouraging early signal, but it does not by itself prove a survival benefit, and longer-term outcome data were still maturing at the latest update
• Dendritic cell vaccines: a patient’s own blood cells are grown into dendritic cells in a lab, exposed to tumor material and given back to build a new immune response. Early studies showed immune responses, but this has not consistently translated into meaningful clinical benefit, and these vaccines are not standard care in the EU

Established Treatment and Experimental Treatment

Treatments are tested in stages. Early trials mainly assess safety and initial activity, while larger randomized trials test whether a treatment improves outcomes compared with standard care. Phase 3 trials often provide the confirmatory evidence used for regulatory decisions, but some treatments can be authorized on earlier evidence when the benefit-risk balance is favorable.

Questions worth asking the treating team:

• Is this treatment already authorized for my cancer type and stage, or still being studied?
• Is the result based on a large randomized trial, or a smaller early-phase study?
• Did the research show a difference in survival or recurrence, or only immune activity in blood tests?
• Would this treatment only be available through a clinical trial?

The table below summarizes where each approach stands.

Key Takeaway

Checkpoint inhibitor immunotherapy has an established role in selected TNBC settings. In early-stage disease, pembrolizumab is used with chemotherapy before surgery and continued afterward; in eligible metastatic disease, pembrolizumab is combined with chemotherapy, or with sacituzumab govitecan, as first treatment. Other approaches remain under study.