# Association of immuno-inflammatory biomarkers with response to neoadjuvant chemotherapy and prognosis in HER2-positive breast cancer: dual-center clinical evidence

**Authors:** Xuanlin Wu, Siqi Wu, Mankai Tang, Longgui Xie, Jianhui Liu, Jiexu Liao, Jie Wang, Huawei Yang

PMC · DOI: 10.3389/fimmu.2026.1751072 · Frontiers in Immunology · 2026-02-09

## TL;DR

This study shows that a blood-based inflammation marker called SII can predict how well HER2-positive breast cancer patients respond to chemotherapy and their long-term survival.

## Contribution

The study identifies the systemic immune-inflammation index (SII) as the strongest predictor among immuno-inflammatory biomarkers for treatment response and prognosis in HER2-positive breast cancer.

## Key findings

- SII had the highest accuracy (AUC = 0.739) in predicting pathological complete response to chemotherapy.
- Low SII was significantly associated with longer disease-free survival (P < 0.001).
- SII's predictive value remained consistent across various patient subgroups.

## Abstract

Peripheral blood immuno-inflammatory biomarkers (IIBs) may help predict response to neoadjuvant chemotherapy (NAC) and prognosis in HER2-positive breast cancer. This study compared the predictive value of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) for pathological complete response (pCR) and disease-free survival (DFS).

A total of 224 female patients with HER2-positive invasive breast cancer who received NAC followed by surgery at two medical centers (2015–2023) were retrospectively analyzed. Baseline IIBs were calculated from complete blood counts. Receiver operating characteristic (ROC) curves identified optimal cut-offs. Logistic and Cox regression analyses combined with the least absolute shrinkage and selection operator (LASSO) method were used to determine factors associated with pCR and DFS. Subgroup analyses were performed to assess consistency across clinical and treatment variables.

SII demonstrated the highest discriminatory ability among tested IIBs for predicting pCR (AUC = 0.739) and was significantly associated with longer DFS (P < 0.001). Patients with low SII had higher pCR rates and improved DFS. These associations remained stable across prespecified subgroups. Other factors related to better response included lower CA15-3/CEA levels, ≥6 NAC cycles, receipt of HER2-targeted therapy, and breast-conserving surgery.

Among common inflammatory indices, SII demonstrated the strongest association with treatment response and prognosis in HER2-positive breast cancer. As an inexpensive, readily available biomarker, it may assist clinical risk stratification. However, given the retrospective design and substantial heterogeneity in treatment regimens, these findings should be interpreted cautiously and validated in prospective studies.

## Linked entities

- **Diseases:** breast cancer (MONDO:0004989), HER2-positive breast cancer (MONDO:0006244)

## Full-text entities

- **Genes:** ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}
- **Diseases:** invasive (MESH:D009361), solid (MESH:D018250), prostatic carcinoma (MESH:D011472), Hepatocellular carcinoma (MESH:D006528), positive (MESH:D000377), pCR (MESH:D005598), overweight (MESH:D050177), pregnancy-associated (MESH:D020150), hepatic artery embolism (MESH:D004617), Breast cancer (MESH:D001943), depression (MESH:D003866), autoimmune diseases (MESH:D001327), toxicity (MESH:D064420), nodal (MESH:D013611), cardiopulmonary diseases (MESH:D006323), metastatic (MESH:D000092182), cT2 tumors (MESH:D009369), immune (MESH:D007154), Stage III disease (MESH:D007676), death (MESH:D003643), colorectal carcinoma (MESH:D015179), DFS (MESH:D011475), Inflammatory (MESH:D007249), Inflammatory Breast Cancer (MESH:D058922), Distant Metastasis (MESH:D009362)
- **Chemicals:** bevacizumab (MESH:D000068258), docetaxel (MESH:D000077143), cyclophosphamide (MESH:D003520), taxane (MESH:C080625), taxanes (MESH:D043823), Pertuzumab (MESH:C485206), THP (MESH:C027260), Trastuzumab (MESH:D000068878), paclitaxel (MESH:D017239), anthracyclines (MESH:D018943), Cb (MESH:D016190), TCbHP (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12926385/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926385/full.md

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Source: https://tomesphere.com/paper/PMC12926385