While immunotherapy holds great potential for triple-negative breast cancer (TNBC), the lack of non-invasive biomarkers to identify beneficiaries limits the application.

Paired baseline, on-treatment, and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center (FUSCC) for sequential high-precision proteomic profiling.

ARG1, NOS3, and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC. Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment. Furthermore, the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.

The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive cancer. Although our previous study classified primary TNBC into four subtypes, comprehensive longitudinal investigations are lacking.

We assembled a large-scale, real-world cohort comprised of 880 TNBC patients [465 early-stage TNBC (eTNBC) and 415 metastatic TNBC (mTNBC) patients] who were treated at Fudan University Shanghai Cancer Center. The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort. Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.

The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1% (47/465). The median overall survival (OS) in the mTNBC cohort was 27.2 months [95% confidence interval (CI), 24.4–30.2 months], which indicated a poor prognosis. The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed. Consistent molecular subtypes were maintained in 77.5% of the patients throughout disease progression with the mesenchymal-like (MES) subtype demonstrating a tendency for subtype transition and brain metastasis. Additionally, a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.

Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression. However, we emphasize the major importance of repeat pathologic confirmation of the MES subtype.