Perioperative Considerations and Cellular Immunotherapy Developments in Breast Cancer

A recent review summarizes evidence for immune checkpoint inhibitors (ICIs) in breast cancer, highlighting the most consistent clinical benefit in triple-negative breast cancer (TNBC), particularly with chemotherapy, alongside discussion of resistance mechanisms, translational biomarkers, and emerging cellular immunotherapy strategies.

In outlining where ICIs currently fit in breast cancer, the authors report that meaningful clinical benefit has been most consistently demonstrated in TNBC when checkpoint blockade is combined with chemotherapy, in contrast to hormone receptor–positive or HER2-positive disease where regulatory approvals have not been secured outside investigational settings. They relate these data to current regulatory positions, noting approvals by agencies such as the FDA and EMA for specific early-stage and metastatic TNBC patient groups, including PD-1/PD-L1–directed approaches used with chemotherapy. Their synthesis highlights that chemotherapy–ICI combinations are presented as a key driver of the current TNBC immune checkpoint inhibitor indications landscape described in the review, rather than as new primary trial reporting.

Against that efficacy backdrop, the review notes that immune overactivation associated with ICIs can result in significant toxicities, sometimes arising before patients experience therapeutic benefit.

The authors describe this timing mismatch as one reason perioperative safety questions can emerge when surgery is planned after neoadjuvant ICI exposure.

The review also notes that immune-related toxicities can be clinically significant and may occur before therapeutic benefit is observed.

They further describe coordination challenges that can arise when immunotherapy is delivered near the time of surgery, framing perioperative planning as a setting where multiple teams may need shared situational awareness of evolving immune-related symptoms and laboratory abnormalities. The discussion emphasizes risk recognition and the possibility that subclinical or early toxicities could affect perioperative readiness, particularly when toxicity onset precedes clinical benefit.

Beyond checkpoint blockade, the review summarizes early-phase cellular immunotherapy modalities under investigation in breast cancer, including CAR-T platforms targeting HER2, ROR1, MUC1, mesothelin, and B7-H3, as well as tumour-infiltrating lymphocyte (TIL) therapy, TCR-engineered T cells, and CAR-NK approaches. The authors highlight translational challenges that include antigen specificity, on-target/off-tumour toxicity risk, and the immunosuppressive tumour microenvironment as recurring barriers to efficacy and safety in solid tumours. They also discuss translational biomarkers used to study response and resistance—such as PD-L1, tumour mutational burden, and TILs—while noting that predictive performance and negative biomarkers remain areas of uncertainty in the literature they review. Within the checkpoint inhibitor evidence base they cite, the authors discuss KEYNOTE-522 as part of the body of data informing TNBC use while positioning cellular therapies and biomarker work as parallel lines of progress with unresolved questions.

Key Takeaways:

• The review describes the clearest clinical benefit for checkpoint inhibitors in TNBC when used with chemotherapy and notes FDA/EMA approvals for selected early-stage and metastatic TNBC patient groups.
• The authors frame perioperative concerns around the observation that immune-related toxicities can arise before clinical benefit, creating potential timing conflicts when surgery follows neoadjuvant ICI exposure.
• The review summarises an active cellular therapy pipeline (CAR-T, TIL, TCR-T, CAR-NK) and discusses PD-L1, TMB, and TILs as studied biomarkers, while describing ongoing uncertainty about predictive value and safety constraints.