Context . Neoadjuvant therapy is the primary treatment for stage II to III breast cancer (BC). The heterogeneity of BC challenges the identification of effective neoadjuvant regimens and of the related sensitive populations. Objective . The study intended to explore the predictive role of inflammatory cytokines, immune-cell subsets, and tumor-infiltrating lymphocytes (TILs) for the accomplishment of the pathological complete response (pCR) after a neoadjuvant regimen. Design . The research team conducted a phase II, singl-earmed, open-label trial. Setting . The study took place at the Fourth Hospital of Hebei Medical University in Shijiazhuang, Hebei, China. Participants . Participants were 42 patients at the hospital receiving treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) between November 2018 and October 2021. Intervention . Participants received neoadjuvant therapy of six cycles of docetaxel, carboplatin, and trastuzumab (TCbH). Outcome Measures . The research team: (1) measured 13 cytokines and immune-cell populations in peripheral blood prior to neoadjuvant therapy administration; (2) measured TILs in tumor tissues; (3) analyzed correlations among biomarkers and pCR. Results . Of the 42 participants, 18 achieved pCR (42.9%) after the neoadjuvant therapy, with 37 having an overall response rate (ORR) of 88.1%. All participants experienced at least one short-term adverse event. The most common toxicity was leukopenia, with 33 participants (78.6%), while no cardiovascular dysfunction occurred. Compared with the non-pCR group, the pCR group had higher serum levels of tumor necrosis factor alpha (TNF-alpha), with P =.013; interleukin 6 (IL-6), with P =.025; and IL-18, with P =.0004. Univariate analysis showed that IL-6 (OR, 3.429; 95% CI,1.838-6.396; P=.0001) had a significant correlation with pCR. Participants in the pCR group had a higher level of natural killer T (NK-T) cells (P =.009) and a lower ratio of cluster of differentiation 4 (CD4):CD8 (P =.0014) before neoadjuvant therapy. Univariate analysis linked a high population of NK-T cells (OR, 0.204; 95% CI,0.052-0.808; P =.018), a low CD4:CD8 ratio (OR, 10.500; 95% CI, 2.475-44.545; P =.001), and TILs expression (OR, 0.192; 95% CI, 0.051-0.731; P =.013) to pCR. Conclusions . Immunological factors, including IL-6, NK-T cells, CD4+ T versus CD8+ T ratio, and TILs expression were significant predictors for response to TCbH neoadjuvant therapy with carboplatin