The advent of antibody-drug conjugates (ADCs) has caused a paradigm shift in breast cancer management, transforming the treatment landscape from advanced lines to curative-intent settings. By integrating the specificity of monoclonal antibodies with the potency of cytotoxic payloads, ADCs have broken the limitations of traditional chemotherapy. This review aims to provide a comprehensive overview of the current state of ADCs in breast cancer, concentrating on targets under development, toxicity, and the challenges that remain to be overcome. Distinct from conventional classifications, we propose a framework categorizing ADC targets into three dimensions based on biological features: oncogenic driver antigens, lineage and oncofetal antigens, and tumor microenvironment antigens. Meanwhile, we discuss the structural evolution of ADCs, the management of toxicity, and the mechanism-based resistance. The future of treatment calls for precise ADC management, the use of next-generation bispecific ADCs and immune-oncology combinations, and the imperative of biomarker-guided sequencing.

Postoperative recurrence of triple-negative breast cancer often starts from residual cells left in an irregular lumpectomy cavity, where a short-lived drug depot is easily washed away and a weak filler gives little structural support. We designed injectable SFMA/MXene/curcumin-loaded mesoporous silica nanoparticle (Cur@MSN) microspheres as a cavity-filling chemophotothermal depot rather than a membrane-like wound dressing. XPS confirmed silica-, curcumin- and MXene-associated signals, including Ti-O contributions in the composite. Mechanical tests showed that MXene/MSN reinforcement increased single-particle stiffness and improved hydrated packed-bed compression resistance, cyclic modulus retention and anti-flushing stability. Curcumin release continued for 14 days, and near-infrared irradiation increased the 32 h release from 68.97 +/- 0.55% to 82.93 +/- 0.45%. Normal 10A and NIH3T3 cells retained high viability, whereas 4 T1 cells showed concentration-dependent inhibition. In vivo thermal screening identified 2.0 mg/mL MXene with 0.50 W/cm(2) irradiation as a mild heating condition (similar to 43 degrees C). In a postoperative 4 T1 model, Cur/MXene microspheres with irradiation reduced bioluminescent tumor signals, supporting a locally retained, mechanically reinforced depot for recurrence-oriented therapy.

Bone is the most common site of distant metastasis in breast cancer (BC), and the development of bone metastasis (BM) is associated with reduced survival. However, reliable clinical models for accurately predicting prognosis in these patients are lacking. Furthermore, the therapeutic benefit of primary site surgery in patients with de novo stage IV breast cancer (DnIV BC) and BM remains controversial. We extracted data for 23,723 patients diagnosed with DnIV BC and BM between 2010 and 2020 from the Surveillance, Epidemiology, and End Results (SEER) database. Using this data, we developed and compared multiple machine learning models to predict survival and the risk of early death. The models were subsequently validated on an independent, multi-center Chinese cohort of 230 patients. We also performed Kaplan-Meier survival analyses before and after propensity score matching to assess the impact of primary tumor surgery. The Light Gradient Boosting Machine (LightGBM) model exhibited promising predictive performance across multiple evaluation settings. On the test dataset, the model’s area under the curve (AUC) of the receiver operating characteristic (ROC) for 12-, 36-, and 60-month survival was 0.775, 0.745, and 0.730, respectively. External validation demonstrated moderate discrimination but reduced performance (AUC drop to 0.67), indicating limited generalizability. In a sensitivity analysis excluding post-diagnostic treatment variables, the model achieved an AUC of 0.768 for early death prediction. External validation of the early death model was not feasible because of the limited number of early death events in the Chinese cohort. Survival analyses showed that primary tumor surgery was associated with improved overall survival after propensity score matching. However, because treatment response and performance status were unavailable, residual confounding and selection bias cannot be excluded. The LightGBM model provides a potentially useful tool for prognostic prediction in DnIV BC patients with BM. Primary tumor surgery was associated with favorable survival outcomes, although causal inference is limited by the retrospective observational design and potential residual confounding.

BACKGROUND:Both domestic and international guidelines recommend using dual tracers and retrieving at least three sentinel lymph nodes (SLNs) for SLN biopsy (SLNB) in patients who are downstaged from clinical N1 lymph node status (cN1) to clinical N0 status after neoadjuvant therapy (NAT). However, because of various limitations, most hospitals in China still perform SLNB using a single blue dye. This discrepancy between guidelines and real-world practice warrants further reflection. METHODS:Adult women who had clinical cT1-cT4, cN1, M0 breast cancer scheduled who were for NAT were eligible. After NAT, patients underwent sequential SLNB and axillary lymph node dissection, with SLNs identified using single dye. The primary end point was the false-negative rate (FNR) of single-dye SLNB. RESULTS:Among 432 patients from 12 centers, single-dye SLNB succeeded in 393 of 432 (90.97%). Pathology revealed node metastases in 201 of 393 patients. The FNR was 8.96% (18 of 201 patients; 95% upper confidence limit, 12.02%). The FNR was lower in women aged 60 years and younger (3.80% vs. 27.91%; p < .0001), and in those with a body mass index (BMI) <25 kg/m2 (4.20% vs. 14.47%; p = .0151), with four or more SLNs (5.19% vs. 16.67%; p = .0152), and with estrogen receptor-negative tumors (3.52% vs. 12.93%; p = .0242). BMI ≥25 kg/m2 (odds ratio, 5.68; 95% confidence interval, 2.05-18.33; p = .0006), estrogen receptor-positive tumors (odds ratio, 3.49; 95% confidence interval, 1.15-12.72; p = .0264) were independently associated with a false-negative SLNB. Examining a greater number of SLNs was independently associated with a lower FNR (odds ratio, 0.65; 95% confidence interval, 0.45-0.90; p =.0088). In hormone receptor-negative/human epidermal growth factor receptor-positive patients, the FNR was 0%. CONCLUSIONS:Single-dye SLNB after NAT in patients initially diagnosed with cN1 breast cancer yielded a clinically acceptable FNR. When four or more SLNs were identified, an additional benefit was observed in patients who had a BMI <25 kg/m2 and negative estrogen receptor status.

Breast cancer patients receiving myelosuppressive chemotherapy are at high risk of febrile neutropenia (FN). Long-acting G-CSFs are recommended for FN prevention, but evidence for mecapegfilgrastim in the dose-dense setting remains limited. This multicenter, prospective, observational, real-world study was conducted at 43 centers in China. Patients with breast cancer who received 2-weekly or 3-weekly chemotherapy with mecapegfilgrastim (6 mg) as prophylaxis for chemotherapy-induced neutropenia were enrolled. The primary outcome was the incidence of FN, defined as an oral temperature of > 38.3 °C or two consecutive readings of > 38.0 °C for 2 h and an absolute neutrophil count (ANC) of < 0.5 × 109/l, or expected to fall below 0.5 × 109/L. The secondary outcomes included severe neutropenia and adverse events (AEs). Between June 2019 and March 2022, a total of 757 patients were enrolled. After 1:2 propensity score matching, 36 patients were included in the 2-weekly group and 71 patients were included in the 3-weekly group. In the first cycle, FN, grade 3/4 neutropenia, and grade 4 neutropenia occurred in 0 (0

PURPOSE:This randomized, double-blind phase 3 equivalence study aimed to evaluate the similarity of neoadjuvant pertuzumab biosimilar HLX11 versus reference pertuzumab plus trastuzumab and docetaxel for human epidermal growth factor receptor 2-positive, hormone receptor-negative early-stage or locally advanced breast cancer (BC). PATIENTS AND METHODS:Eligible patients were randomly assigned (1:1) to receive 4 cycles of neoadjuvant HLX11 (HLX11 arm) or European Union-sourced pertuzumab, plus trastuzumab and docetaxel (EU-pertuzumab arm). Patients in the respective arms received adjuvant HLX11 plus trastuzumab or were re-randomized (1:1) to receive HLX11 or EU-pertuzumab plus trastuzumab. The primary endpoint was blinded independent central review (BICR)-assessed total pathological complete response (tpCR) rate. RESULTS:In total, 908 patients were randomized to the HLX11 (n = 454) or EU-pertuzumab arm (n = 454); 192 patients in HLX11 arm received adjuvant HLX11; 200 patients in EU-pertuzumab arm were re-randomized to receive adjuvant HLX11 (n = 100) or EU-pertuzumab (n = 100). BICR-assessed tpCR rate (95% confidence interval [CI]) was 46.3% (41.6%-51.0%) and 45.8% (41.2%-50.5%), respectively. The equivalence criteria were met, with relative risk of tpCR (90% CI) of 1.01 (0.90-1.14) and relative difference (95% CI) of 0.47% (-5.99%-6.92%). No clinically meaningful differences were observed in other efficacy endpoints, safety, pharmacokinetics (PK), or immunogenicity. In the adjuvant phase, switching from EU-pertuzumab to HLX11 led to no notable differences in safety, PK, or immunogenicity. CONCLUSIONS:Compared with EU-pertuzumab, neoadjuvant HLX11 demonstrated a similar tpCR rate and no clinically meaningful differences in other efficacy endpoints, safety, PK, or immunogenicity in BC.

IMPORTANCE:The combination of neoadjuvant taxanes with trastuzumab and pertuzumab remains the cornerstone treatment strategy in ERBB2-positive breast cancer. Anbenitamab (a ERBB2-biparatopic antibody that induces profound receptor clustering) and HB1801 (a solvent-free albumin-bound docetaxel), have shown promising antitumor activity and an acceptable safety profile in patients with breast cancer. OBJECTIVE:To evaluate whether neoadjuvant anbenitamab combined with HB1801 could improve efficacy without increasing toxic effects for patients with early ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS:This multicenter, phase 3 registrational randomized clinical trial enrolled patients with stage II or III ERBB2-positive breast cancer from 61 hospitals in China between December 19, 2024, and August 29, 2025 (data cutoff: January 28, 2026). Data were analyzed from February 1 to March 20, 2026. INTERVENTIONS:Patients were randomly assigned (1:1) to receive 6 cycles of neoadjuvant anbenitamab plus HB1801, with or without carboplatin (investigational group), or trastuzumab, pertuzumab, and docetaxel, with or without carboplatin (control group). MAIN OUTCOMES AND MEASURES:The primary end point was total pathological complete response (tpCR) assessed by a blinded independent review committee. RESULTS:Among 521 included patients (median [IQR] age, 52.0 [23-79] years), 263 were randomized to the investigational group and 258 to the control group. The tpCR rate was significantly higher in the investigational group than the control group (164 patients [62.4%] vs 132 patients [51.2%]; absolute difference, 11.4 [95% CI, 3.2 to 19.6] percentage points; P = .004). Benefit was consistent across subgroups, including subgroups with hormone receptor-positive disease (77 patients [51.7%] vs 63 patients [44.4%]), hormone receptor-negative disease (87 patients [76.3%] vs 69 patients [59.5%]), early-stage disease (111 patients [63.8%] vs 87 patients [51.8%]), locally advanced disease (53 patients [59.6%] vs 45 patients [50.0%]), with carboplatin treatment (74 patients [66.7%] vs 61 patients [54.5%]), and without carboplatin treatment (90 patients [59.2%] vs 71 patients [48.6%]). Grade 3 or 4 treatment-related adverse events occurred in 77 patients (29.3%) in the investigational group and 73 patients (28.3%) of the control group. No treatment-related deaths occurred. CONCLUSIONS AND RELEVANCE:This randomized clinical trial found that neoadjuvant anbenitamab and HB1801 in patients with breast cancer significantly improved the tpCR rate compared with standard therapy with a highly manageable safety profile. This new combination may offer an improved treatment option, although long-term survival follow-up analyses are warranted. Trial Registration:ClinicalTrials.gov Identifier: NCT06747338.

Background: For early or locally advanced TNBC, preferred neoadjuvant strategies include a four-drug chemotherapy regimen containing anthracyclines, cyclophosphamide, taxanes, and platinum. Accumulating evidence suggests that blockade of the PD-1/PD-L1 pathway may enhance the efficacy of conventional neoadjuvant chemotherapy. Camrelizumab is an anti-PD-1 antibody that has demonstrated antitumor activity in advanced or metastatic TNBC. Herein, we conducted a double-blind, randomized phase 3 trial (NCT04613674) to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemo in early or locally advanced TNBC. Methods: Patients with previously untreated, invasive stage II (T2N0-1M0/T3N0M0) or III (T2N2-3M0/T3N1-3M0) TNBC were randomized (1:1) to receive neoadjuvant camrelizumab (200 mg, Q2W) or placebo plus chemo (nab-paclitaxel [100 mg/m2, D1, D8, D15, Q4W] + carboplatin [AUC 1.5, D1, D8, D15, Q4W] for 16 weeks, followed by dose-dense epirubicin [90 mg/m2, Q2W] + cyclophosphamide [500 mg/m2, Q2W] for 8 weeks). Randomization was stratified by tumor clinical stage (stage II vs III) and PD-L1 expression (combined positive score [CPS] <10 vs ≥10). After surgery, patients allocated to the camrelizumab group received camrelizumab (200 mg, Q2W) for up to a year (from first dose). The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). Secondary endpoints included event-free survival (EFS), disease-free survival (DFS), distant disease-free survival (DDFS), and pre-surgery objective response rate (ORR; per RECIST v1.1). Results: As of data cutoff (Sep.30, 2023), 441 patients were randomized and treated (camrelizumab, n=222; placebo, n=219). Median follow-up was 14.4 mo. Overall, median age was 48.2 years; 35.8% of patients had stage III disease at baseline, and 70.5% presented with nodal involvement (N3 disease, 9.1%). pCR rate was 56.8% (95% CI 50.0-63.4) with camrelizumab + chemo and 44.7% (95% CI 38.0-51.6) with placebo + chemo (rate difference, 12.2% [95% CI 3.3 to 21.2]; 1-sided p=0.0038). The benefit in pCR with camrelizumab + chemo was observed regardless of PD-L1 expression, nodal status or disease stage at baseline. Specifically, among patients with poor prognostic factors, the pCR rate with camrelizumab + chemo vs placebo + chemo was 57.8% (89/154) vs 42.7% (67/157) for node-positive disease (rate difference, 15.1% [95% CI 4.1 to 26.1]), and 49.4% (39/79) vs 38.0% (30/79) for stage III disease (rate difference, 11.4% [95% CI -4.0 to 26.8]). Pre-surgery ORR reached 87.4% (95% CI 82.3 to 91.5) with camrelizumab + chemo and 82.6% (95% CI 77.0 to 87.4) with placebo + chemo. EFS (HR, 0.80 [95% CI 0.46-1.42]), DFS (HR 0.58 [95% CI 0.27 to 1.24]) and DDFS (HR 0.62 [95% CI 0.29-1.33]) were immature, with a trend favoring the camrelizumab + chemo group. Across stages, TRAEs of grade ≥3 occurred in 90.1% of patients in the camrelizumab + chemo group vs 82.6% in the placebo + chemo group; all events with incidence ≥10% were hematological toxicities. Conclusions: Addition of camrelizumab to platinum-containing intensive neoadjuvant chemotherapy significantly improved pCR rate in early or locally advanced TNBC, with a manageable safety profile. Early survival data also favored the camrelizumab + chemo group. Citation Format: Zhi-Ming Shao, Li Chen, Hui Li, Hao Zhang, Huawei Yang, Jun Qian, Zhihua Li, Yu Ren, Shu Wang, Peifen Fu, Hongjian Yang, Yunjiang Liu, Jing Sun, Jianyun Nie, Ruiwen Lei, Yongzhong Yao, Anqin Zhang, Shouman Wang, Xiaopeng Ma, Zhong Ouyang, Hongwei Yang, Song-Yang Wu, Shuo-Wen Cao, Kun Wang, Aimei Jiang, Quchang Ouyang, Da Pang, Limin Wei, Xiaoming Zha, Yu Shen, Xiangwen Qu, Fei Wu, Xiaoyu Zhu, Zhong-Hua Wang, Lei Fan & the CamRelief Study Group. Neoadjuvant camrelizumab plus chemotherapy (chemo) for early or locally advanced triple-negative breast cancer (TNBC): a randomized, double-blind, phase 3 trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr GS3-06.

Background: Given the known complications associated with axillary lymph node dissection (ALND) and the limited application of radiolabeled colloid tracking in China, dye-only sentinel lymph node biopsy (SLNB) is proposed as a feasible and alternative surgical treatment strategy for patients with initially clinically node-positive (cN1) breast cancer to a clinically node-negative (ycN0) status after neoadjuvant therapy (NAT). However, the clinical diagnostic performance of dye-only SLNB needs further verification. Methods: We conducted a multicenter diagnostic clinical trial from July 2019 to September 2023 by recruiting 230 patients from 12 participating centers across six provinces in China. Adult women with clinical stage T1-4N1M0 breast cancer and ycN0 status after NAT were eligible. SLNB and ALND were performed sequentially for patients, while a single dye was used to guide sentinel lymph nodes during the operation. The primary endpoint was the false-negative rate (FNR) of SLNB after NAT in women with ycN0 disease. Furthermore, subgroup analyses were conducted by age, body mass index (BMI), the number of SLNs removed and tumor subtype. The trial is registered on www.chictr.org.cn (identifier: ChiCTR1900026929) and www.isrctn.com (identifier: ISRCTN31364289). Findings: The detection rate of single-dye was 95.22% (219/230). Pathological examinations showed positive lymph node findings in 117 of 230 patients. SLNB was successful in 212 out of the 219 patients (96.80%). The FNR of dye-alone SLNB was 5.98% (7/117; 95% CI, 2.44%-11.94%). Furthermore, the FNR was lower in women under 60 years of age (2.33% vs. 16.13% older than 60 years, P=0.0139), with body mass index under 25 kg/m2 (2.60% vs. 12.5%, P=0.0452), and with four or more SLNs (2.53% vs. 13.16% with fewer than four SLNs, P=0.0358). For HR negative/HER-2 positive cases, the FNR was 0%. Interpretation: SLNB with dye alone in patients with initially cN1 breast cancer and ycN0 after neoadjuvant therapy resulted in clinically acceptable rate of FNR. When four or more SLNs are detected, patients with age ≤ 60 years, BMI<25km/m2 and Her2-positive would derive additional benefit from dye-alone SLNB. Funding: This trial was funded by Tackling Key Problems and Serving Local Projects of Liaoning Province (ZF20190006, to BC), National Natural Science Foundation of China (82073282 and 82203873, to AZ) and Joint Fund Project of the Science and Technology Program of Liaoning Province (2023012141-JH3/4600, to AZ).

Importance:Preferred neoadjuvant strategies for early or locally advanced triple-negative breast cancer include a 4-drug chemotherapy regimen containing anthracyclines, cyclophosphamide, taxanes, and platinum. Blockade of the programmed death receptor 1/ligand-1 (PD-1/PD-L1) pathway may improve efficacy of classic neoadjuvant chemotherapy. Camrelizumab, an anti-PD-1 antibody, has showed antitumor activity in advanced triple-negative breast cancer. Objective:To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy for patients with early or locally advanced triple-negative breast cancer. Design, Setting, and Participants:This randomized, double-blind, phase 3 trial enrolled patients from 40 hospitals in China between November 25, 2020, and May 12, 2023 (data cutoff: September 30, 2023). A total of 441 eligible patients were enrolled. Interventions:Patients were randomized in a 1:1 ratio to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks. The chemotherapy included nab-paclitaxel (100 mg/m2) and carboplatin (area under the curve, 1.5) on days 1, 8, and 15 in 28-day cycles for the first 16 weeks followed by epirubicin (90 mg/m2) and cyclophosphamide (500 mg/m2) every 2 weeks for 8 weeks. Main Outcomes and Measures:The primary end point was pathological complete response (defined as no invasive tumor in breast and lymph nodes [ypT0/Tis ypN0]). Results:Among 441 females randomized (median age, 48 years), the median (range) follow-up duration from randomization was 14.4 (0.0-31.8) months. Pathological complete response was achieved in 126 patients (56.8% [95% CI, 50.0%-63.4%]) in the camrelizumab-chemotherapy group and 98 patients (44.7% [95% CI, 38.0%-51.6%]) in the placebo-chemotherapy group (rate difference, 12.2% [95% CI, 3.3%-21.2%]; 1-sided P = .004). In the neoadjuvant phase, adverse events of grade 3 or higher occurred in 198 patients (89.2%) in the camrelizumab-chemotherapy group and 182 (83.1%) in the placebo-chemotherapy group; serious adverse events occurred in 77 patients (34.7%) in the camrelizumab-chemotherapy group and 50 (22.8%) in the placebo-chemotherapy group, with fatal adverse events occurring in 2 patients (0.9%) in the camrelizumab-chemotherapy group. Conclusions and Relevance:Among patients with early or locally advanced triple-negative breast cancer, the addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response. Trial Registration:ClinicalTrials.gov Identifier: NCT04613674.

Elevated ferritin levels in breast invasive carcinoma correlate strongly with unfavorable clinical outcomes. However, current ferritin-reducing strategies (e.g., CRISPR, PROTACs) are limited by inefficient large protein aggregate degradation and poor cancer cell specificity. Ferritinophagy-an intrinsic ferritin-lowering process that supplies intracellular iron via autophagy-can induce ferroptosis when dysregulated. Inspired by this mechanism, we engineered Ferritin NanoChaperone (FerriNano), which consists of a ferritin-homing peptidefunctionalized nanoceria, (HK-CeO2) coated with hyaluronic acid (HA). Upon administration, FerriNano selectively accumulated in 4T1 tumor tissues via the interaction between HA and CD44 on cancer cells. The nanochaperone, HK-CeO2, can selectively bind to overexpressed ferritin, and the formed complex can be sequestered in autophagosomes by in situ autophagy activation of nanoceria, which subsequently fuse with lysosomes to execute ferritin degradation. Consequently, FerriNano demonstrated potent downregulated ferritin levels and reduced tumor metastasis. Notably, approximately 3.7 % of the administered FerriNano traversed the intestinal epithelium via hepatic bile secretion. This systemic distribution enhanced gut microbiota diversity and metabolic activity, potentially amplifying therapeutic outcomes through microbiota-immune interactions. Overall, this study not only identifies candidate nanochaperones for targeted ferritin degradation but also highlights the significance of evaluating the metabolic byproducts for breast cancer treatment.

We have developed a high-speed dual-modal imaging system (HDMI), designed to concurrently reveal anatomical and hematogenous details of the human breast within seconds. Through innovative system design and technical advancements, HDMI integrates large-view photoacoustic and ultrasonic computed tomography with standardized scanning and batch data processing for computer-aided diagnosis. It achieves dual-modal imaging at a 10-hertz frame rate and completes a whole-breast scan in 12 seconds, providing penetration up to 5 centimeters in vivo. In a clinical study involving 170 patients with 186 breast tumors, we developed a diagnostic model leveraging combined photoacoustic and ultrasound features. In a triple-blinded comparison using pathological diagnosis as the ground truth, HDMI significantly improved diagnostic specificity from 22.5 to 75.0% compared to clinical ultrasonography. This technology shows strong potential for early breast tumor diagnosis, offering enhanced accuracy without the need for ionizing radiation, exogenous contrast agents, pain, invasiveness, operator dependence, or extended examination times.

Background: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Effective approach stratifying the risk of recurrence for early-stage TNBC patients is still lacking. This study aims to explore the molecular heterogeneity of early-stage TNBC yielding a practical tool evaluating the risk of disease recurrence. Methods: This retrospective study included stage I-III TNBC patients treated at our institution between December 2013 and December 2019. RNA sequencing was performed on surgical samples, and correlations were analyzed with clinical data and prognosis. Results: A total of 240 patients were included, with a median follow-up of over 5 years. Patients were categorized into two cohorts: recurrence-free within 3 years post-surgery (good prognosis, n=203) and recurrence within 3 years (bad prognosis, n=34). Differential gene analysis revealed 423 up-regulated and 1,818 down-regulated genes in patients with good prognosis. Consensus cluster analysis identified three clusters (C1, C2, C3). C1 had the worst prognosis for DFS (p=0.020) and OS (p=0.055). Further analysis of the three groups' characteristics showed that C1 patients exhibited significant upregulation of angiogenesis, hypoxia, and glycolysis signals. Differential gene analysis indicated that NOX1, HNF1A, CXCL8, TGFBI, and NT5E (CD73) were significantly upregulated in C1 patients. This suggests that tumors in these patients might create a hypoxic microenvironment through NOX1 upregulation, promoting glycolysis and adenosine metabolism, which in turn stimulates ATP and lactate release, angiogenesis, and immune evasion, creating a tumor growth-promoting microenvironment. Given the notably shorter DFS in this group, therapies targeting angiogenesis or CD73 may improve clinical outcome of C1 patients. C2 patients showed enrichment of canonical oncogenic pathways like WNT, NOTCH signaling. C3 patients displayed pro-inflammatory tumor microenvironment with elevated IFN-γ signatures. Additionally, potential infiltration of activated dendritic cells, activated CD8+ T cells, CD4+ T cells, and plasma cell signature (IGHV1OR15-2, IGKV1D-43, IGHV2-26) were observed in the C3 group. This deconvoluted estimation of TME indicated the presence of matured tertiary lymphoid structures (TLS) in the C3 group. Eight subtype and prognosis related genes (ABCD2, ACSM3, ADCYAP1, ADM, CXCL13, GLO1, PIGR, RRP8) were selected. A prognostic prediction model was constructed, categorizing patients into high-risk and low-risk groups. In the training set (n=166), high-risk patients had significantly lower OS than low-risk patients (P<0.0001), with an AUC of 0.874 for predicting 3-year recurrence. The validation set (n=71) showed an AUC of 0.844, with high-risk patients having significantly lower OS (P<0.0001). External validation with the GSE103191 dataset showed an AUC of 0.761 for predicting 3-year survival. Conclusions: This study disclosed novel molecular subtypes with prognostic and therapeutic significance. A subtype-derived prognostic model was also constructed and validated to stratify recurrence risk for early-stage TNBC patients. Further validation via multi-center study was warranted. Citation Format: Haixing Shen, Qing Chen, Jing Zhang, Shuqian Wang, Jing Zhao, Changbin Zhu, Xiaotian Zhang, Xing Li, Tianze Yu, Jinfei Ma, Yanyuan Li, Peifen Fu. Revealing prognostic subtypes and related model of early-stage TNBC [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-05-27.

Mecapegfilgrastim has been previously validated for efficacy and safety in neutropenia prevention during clinical trials. This nationwide, real-world study (RWS) evaluates its role in protecting against moderate to severe chemotherapy-induced neutropenia (CIN) in Chinese patients with non-myeloid malignancies. In this prospective study conducted in the 46 centers across China, the patients with non-myeloid malignancies were enrolled, and received subcutaneous injections of mecapegfilgrastim 24 h after each chemotherapy cycle. Outcomes were monitored over four subsequent chemotherapy cycles. The primary outcome was safety, while secondary outcomes included the incidence of grade 3 or higher neutropenia, grade 4 neutropenia, and febrile neutropenia (FN), etc. From June 2019 to March 2022, 2,859 patients were enrolled, contributing to 7,763 observed chemotherapy cycles. Treatment-related adverse events (TRAEs) were noted in 329 patients (11.5

Background:To investigate the efficacy and safety of adding tislelizumab to neoadjuvant chemotherapy with nab-paclitaxel and carboplatin (TP) followed by adjuvant tislelizumab for early TNBC to explore the optimal neoadjuvant chemotherapy backbone and courses. Methods:The cTRIO study (ChiCTR2100041675) is a multicenter, prospective, open-label phase II trial across 8 sites in China, evaluating the efficacy and safety of neoadjuvant tislelizumab plus TP followed by adjuvant tislelizumab in patients with early triple-negative breast cancer (TNBC). We included women aged ≥18 years with histologically confirmed early TNBC defined by estrogen receptor immunohistochemistry (IHC) with T1 N1-3 or T2-4 N0-3 stage. Participants received six cycles of neoadjuvant tislelizumab (200 mg on day 1) plus nab-paclitaxel and carboplatin (TP; 125 mg/m2 on days 1 and 8), definitive surgery 3-6 weeks after completion of neoadjuvant therapy, followed by adjuvant tislelizumab every 3 weeks for 1 year. The primary endpoint was pathologic complete response (pCR). Findings:Sixty-two patients were enrolled from March 2021 to October 2022, including 44 cases with programmed cell death ligand 1 (PD-L1) positive and 9 cases at N3. At final analysis, 35/62 patients had achieved pathologic complete response (pCR, 56%; 95% confidence interval [CI], 43%-69%), with 33% (3/9) of N3 cases achieving pCR. The 3-year EFS and OS rates were 82.2% (95% CI, 70.2%-89.7%) and 87.7% (95% CI, 75.6%-94.0%), respectively. The incidence rates of grade ≥3 treatment-related adverse events (TRAEs) and grade ≥3 immune-related adverse events (irAEs) were 53% (33/62) and 5% (3/62), respectively. Patients with a higher PD-L1 combined positive score were less likely to experience relapse (P = 0.0090). Interpretation:Despite being a de-escalating and anthracycline-free neoadjuvant treatment approach, the triplet combination therapy showed promising efficacy and safety, signifying a crucial step toward the optimization of chemoimmunotherapy for early TNBC. Funding:This study was supported by BeOne Medicines, Ltd.