Immunotherapy for breast cancer is a treatment that helps your immune system recognize and attack cancer cells it would otherwise miss. Unlike chemotherapy, which directly kills fast-growing cells, immunotherapy removes the “brakes” that cancer cells put on your immune response, or trains immune cells to target tumors more effectively. It is currently approved and most widely used for triple-negative breast cancer (TNBC), a subtype that accounts for about 10 to 15% of all breast cancers.
How Immunotherapy Works Against Breast Cancer
Cancer cells survive partly by hiding from the immune system. They do this by displaying proteins on their surface that send a “stand down” signal to T cells, the immune cells responsible for hunting and killing threats. The most important of these proteins in breast cancer is called PD-L1. When PD-L1 on a cancer cell connects with a receptor called PD-1 on a T cell, it essentially switches the T cell off, letting the tumor grow unchecked.
Checkpoint inhibitors, the main type of immunotherapy used in breast cancer today, block that connection. By preventing PD-L1 from binding to PD-1, the drug reactivates T cells so they can recognize the cancer as a threat and attack it. Think of it as removing a disguise: the cancer cells were always there, but now your immune system can finally see them.
A second checkpoint pathway involves a protein called CTLA-4, which dampens immune activation at an earlier stage. Blocking CTLA-4 boosts T cell activity and proliferation. While CTLA-4 inhibitors are used in other cancers, current breast cancer treatment focuses on the PD-1/PD-L1 pathway.
Which Breast Cancers Respond to Immunotherapy
Immunotherapy works best in triple-negative breast cancer. TNBC lacks the three receptors (estrogen, progesterone, and HER2) that other breast cancer treatments target, which historically made it harder to treat. However, TNBC tumors tend to carry more genetic mutations and attract more immune cells into the tumor environment, making them more visible to an immune system that’s been “unlocked” by checkpoint inhibitors.
Not every TNBC patient qualifies. For metastatic or locally advanced TNBC that can’t be surgically removed, your tumor needs to be tested for PD-L1 expression using a scoring system called the Combined Positive Score (CPS). A CPS of 10 or higher indicates enough PD-L1 is present for immunotherapy to provide a meaningful benefit. For early-stage TNBC treated before surgery, immunotherapy can be used more broadly regardless of PD-L1 score.
For HER2-positive breast cancer, checkpoint inhibitors are not currently approved, though there is strong biological rationale for studying them. HER2-positive tumors have relatively high mutation rates and moderate levels of immune cell infiltration, and clinical trials are actively exploring whether adding immunotherapy improves outcomes. Hormone receptor-positive breast cancers generally have lower immune cell activity and remain the least likely subtype to benefit from current immunotherapy approaches.
Approved Drugs and How They’re Used
The main immunotherapy drug used in breast cancer is pembrolizumab (brand name Keytruda), a PD-1 inhibitor. It is FDA-approved in two settings for TNBC:
- Early-stage TNBC: Pembrolizumab is given alongside chemotherapy before surgery (neoadjuvant treatment), then continued alone after surgery (adjuvant treatment) to reduce the risk of the cancer returning.
- Metastatic TNBC: Pembrolizumab is combined with chemotherapy as a first-line treatment for patients whose tumors have a PD-L1 CPS of 10 or higher.
Atezolizumab (Tecentriq), a PD-L1 inhibitor, was also previously approved for metastatic TNBC but has seen its role narrow as pembrolizumab became the preferred option based on stronger trial data.
Pembrolizumab is given as an intravenous infusion, typically every three weeks or every six weeks depending on the dosing schedule your oncologist selects. Each infusion session itself is relatively short compared to many chemotherapy regimens. In the early-stage setting, the full course of treatment spans several months: chemotherapy plus immunotherapy before surgery, followed by additional immunotherapy cycles after surgery.
How Well It Works
The landmark KEYNOTE-522 trial tested pembrolizumab combined with chemotherapy in early-stage TNBC. The results showed a clear benefit: the estimated five-year event-free survival was 81.2% for patients who received pembrolizumab plus chemotherapy, compared to 72.2% for those who received chemotherapy alone. That nine-percentage-point improvement represents a 35% reduction in the risk of cancer returning or progressing.
In the metastatic setting, the KEYNOTE-355 trial found that adding pembrolizumab to chemotherapy significantly improved both progression-free survival and overall survival for patients with a PD-L1 CPS of 10 or more. This combination is now considered the standard first-line treatment for that group.
Side Effects to Expect
Because immunotherapy works by amplifying the immune system, the most notable side effects happen when the immune response overshoots and attacks healthy tissues. These are called immune-related adverse events, and they can affect almost any organ system, though some patterns are much more common than others.
In a real-world study of 100 early TNBC patients receiving pembrolizumab, the most frequent immune-related side effects were hormonal disruptions (endocrinopathies), occurring in 52% of patients. These typically involve the thyroid gland, either becoming underactive or overactive, and are usually manageable with hormone replacement medication that you may need to continue long-term. Digestive issues came next at 23%, with colitis (inflammation of the colon causing diarrhea and abdominal pain) affecting about 10% of patients. Lung inflammation (pneumonitis) occurred in 6%, and skin rashes in 4%.
Most side effects are mild to moderate. However, about 13% of patients in clinical trials experienced severe immune-related events (grade 3 or higher), with gastrointestinal problems being the most common severe reaction. Severe events typically require hospitalization and may mean pausing or stopping immunotherapy. Your care team will monitor bloodwork and symptoms closely throughout treatment, and catching these reactions early makes them much easier to treat.
How Immunotherapy Differs From Other Treatments
The side effect profile of immunotherapy feels different from chemotherapy. You’re less likely to experience the classic chemotherapy effects like severe nausea, hair loss, or dangerously low blood counts from the immunotherapy component itself (though these still occur from the chemotherapy given alongside it). Instead, the immune-related side effects can show up in unexpected places, like your thyroid or your lungs, and they can appear weeks or even months after treatment ends.
The other key difference is the goal. Chemotherapy kills cancer cells directly but stops working when you stop the drug. Immunotherapy aims to “teach” your immune system to recognize the cancer, which can provide a more durable response. This is part of why it’s given both before and after surgery in the early-stage setting: to prime the immune system, then reinforce that immune memory.
Beyond Checkpoint Inhibitors
Checkpoint inhibitors are the only immunotherapy approach currently approved for breast cancer, but several other strategies are in development. Cancer vaccines aim to train the immune system to recognize specific proteins found on breast cancer cells. One early-phase trial is testing a vaccine targeting alpha-lactalbumin, a protein associated with TNBC, in patients who have completed initial treatment and are cancer-free but at risk for recurrence. The idea is preventive: prime the immune system to attack cancer cells if they ever reappear.
Other experimental approaches include adoptive cell therapy, where immune cells are removed from your body, modified or expanded in a lab to better fight cancer, and then infused back. Bispecific antibodies, which physically link T cells to cancer cells to force an immune attack, are also being studied. These approaches are still in clinical trials and not yet part of standard breast cancer care.