Background and Importance Immunotherapy is used in advanced cancers, but its use in early stages is a new area of study. Neoadjuvant therapy (NAT) with immune checkpoint inhibitors (ICIs) could be advantageous, stimulating the immune response before surgery.

Aim and Objectives To evaluate the efficacy of ICIs-based NAT in the early stages of breast cancer (BC).

Material and Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Pubmed was consulted to identify all clinical trials published between January 2018-August 2023 that included patients with resectable early-stage BC, who were treated with ICIs in monotherapy or combined with chemotherapy prior to surgery.

Only those reporting efficacy data, such as pathological complete response (pCR) and disease-free survival were included, alongside phase-2 and phase-3 trials. Article selection and data extraction was carried out by peer review and the evaluation of discrepancies was done by a third party.

Results Seven studies met the inclusion criteria: four included patients with triple-negative histology, one included both triple-negative and hormone receptor (HR) positive/human epidermal growth factor 2 (HER-2) negative receptors. One included HER-2 positive patients and another included patients with Luminal B-like (LumB-like) molecular histology.

3 studies used PD-1 inhibitors and 4 used PD-L1 inhibitors. Additionally, 3 studies continued adjuvant treatment with ICIs. In the GeparNuevo trial, durvalumab improved survival despite a modest increase in pCR.

In Keynote-522, chemotherapy+pembrolizumab resulted in increased pCR and event-free survival in patients with triple-negative breast cancer (TNBC).

The I-SPY2 study explored multiple treatments in high-risk BC, showing benefits of pembrolizumab in patients with different molecular subtypes (HER-2 negative, HR positive/HER-2 negative and TNBC)

In IMpassion031, chemotherapy+atezolizumab increased the pCR rate in TNBC patients. These results were consistent with NeoTRIP.

For HER-2 positive BC, NeoPATH suggested that immunotherapy-chemotherapy combination could be beneficial, especially in HR negative and PD-L1 positive patients.

In the GIADA-trial evaluating nivolumab in LumB-like BC, the hypothesis for pCR rate was not met.

Conclusion and Relevance Although immunotherapy shows promising advances in NAT, especially in TNBC, since it is the most immunogenic subtype, more research is needed to better understand its mechanisms and find predictive biomarkers of response. Currently, pembrolizumab is used in TNBC according to Keynote-522.

Conflict of Interest No conflict of interest.