e12623 Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis and limited treatment options due to the lack of targeted therapies. Chemotherapy is the standard treatment for TNBC, but its efficacy remains unsatisfactory. Recent advances in immunotherapy have shown promise in improving treatment outcomes. This study aimed to evaluate the clinical efficacy and safety of camrelizumab, an anti-PD-1 antibody, combined with apatinib and chemotherapy as neoadjuvant therapy in patients with stage II-III TNBC. Methods: In this single-center, prospective, non-randomized clinical trial, patients with newly diagnosed stage II-III TNBC in West China Hospital received a combination of camrelizumab (200 mg intravenouly every 2 weeks), apatinib (250 mg orally daily), and alternating chemotherapy (4 cycles of albumin paclitaxel and 4 cycles of epirubicin plus cyclophosphamide) for 8 cycles. The primary endpoint was pathological complete response (pCR), and secondary endpoints included overall response rate (ORR), and treatment-related adverse events (AEs). Results: A total of 35 patients were enrolled from June 2023 to April 2024, of which one patient withdrew from the study due to intolerance to adverse reactions. At the end of the treatment, the total pCR (ypT0/is ypN0) rate was 67.6% (23/34), and the bpCR (ypT0/is) rate was 70.6% (24/34). The tpCR rate of PD-L1 positive subgroup was higher than that of PD-L1 negative group (66.7% vs. 50.0%). The ORR at the end of neoadjuvant treatment was 94.1% (32/34). The most common grade 3-4 adverse events were elevated levels of alanine aminotransferase (38.2%) and aspartate aminotransferase (29.4%), and no significant toxicities or treatment-related deaths were observed. Conclusions: Camrelizumab and apatinib combined with chemotherapy as neoadjuvant treatment for stage II-III TNBC has high clinical efficacy and favorable safety, which is worthy of further investigation and clinical application. Clinical trial information: NCT05447702 .

HER2-low breast cancer lacks effective targeted options in the curative setting. We evaluated the efficacy, safety, and exploratory biomarker correlates of neoadjuvant disitamab vedotin (HER2-targeted antibody–drug conjugate) plus penpulimab (PD-1 inhibitor) in stage Ⅱ–Ⅲ disease (NCT05726175). In a prospective single-arm study, patients with newly diagnosed stage II–III HER2-low breast cancer (IHC 1 + or 2+/FISH−) received disitamab vedotin plus penpulimab every 3 weeks for six cycles before surgery. The primary end point was pathologic complete response (pCR). Secondary end points included objective response rate (ORR) and safety. Exploratory analyses incorporated multi-omic profiling (proteomics, multiplex immunofluorescence, RNA sequencing) and integrative modeling to derive predictive biomarkers. In the per-protocol set, pCR was 25.0% (4/16) and ORR 56.3% (9/16). At surgery, 31.3% achieved residual cancer burden (RCB) 0–1. Numerically higher pCR rates were seen in PD-L1–positive versus –negative tumors (33.3% v 14.3%) and in HER2 IHC 2+/FISH − versus IHC 1 + tumors (37.5% v 12.5%). Treatment was generally well tolerated: grade ≥ 3 events occurred in 25%, with no treatment-related deaths. Exploratory multi-omics yielded a baseline response prediction model (BRPscore; CCL19 + M2/M1 macrophage ratio) that correctly discriminated all pCR cases with strong discriminatory capacity (AUC 0.89), and identified MCP-1 as the most consistent biomarker across timepoints. In conclusion, neoadjuvant disitamab vedotin plus penpulimab produced a 25% pCR with manageable safety in stage II–III HER2-low breast cancer. The integration of a BRPscore with MCP-1 as a dynamic biomarker provides proof-of-concept for biomarker-driven patient selection and adaptive monitoring, supporting further randomized evaluation of ADC–ICI combinations.

e12620 Background: HER2-low expressing breast cancer represents a heterogenous subtype with limited targeted therapeutic options. Disitamab Vedotin, a novel HER2-targeted antibody-drug conjugate (ADC), and Penpulimab, an anti-PD-1 monoclonal antibody, have both demonstrated potential in various cancer treatment contexts. This study aims to assess the clinical efficacy and safety of Disitamab Vedotin in combination with Penpulimab as neoadjuvant therapy in patients with HER2-low expressing, stage II-III breast cancer. Methods: This single-center, prospective, non-randomized clinical trial enrolled patients with newly diagnosed HER2-low expressing (IHC 1+ or 2+ without amplification by FISH), stage II-III breast cancer in West China Hospital. All patients received neoadjuvant treatment with Disitamab Vedotin (2.0 mg/kg IV) and Penpulimab (200 mg IV) every 3 weeks for a total of 6 cycles, followed by surgery. The primary endpoint was pathological complete response (pCR), and secondary endpoints included overall response rate (ORR) and treatment-related adverse events (AEs). Results: From August 2023 to August 2024, a total of 20 patients were enrolled in the study, with two patients withdrawing due to intolerance to adverse reactions and two others discontinued due to disease progression. At the end of the treatment, the total pCR (ypT0/is ypN0) rate was 25.0% (4/16). The ORR reached 56.3% (9/16) by the clinical response assessment at the end of neoadjuvant treatment. The PD-L1 positive subgroup demonstrated a higher tpCR rate compared to the PD-L1 negative subgroup (33.3% vs. 14.3%). Additionally, the IHC 1+ subgroup exhibited a lower tpCR rate than the IHC 2+ subgroup without amplification by FISH (11.1% vs. 42.9%). The most common AEs were constipation (43.8%) and itching (37.5%), with one reported serious adverse event (SAE) of herpes zoster, and no significant toxicities or treatment-related deaths observed. Conclusions: While the clinical benefit may be somewhat limited, the combination of Disitamab Vedotin and Penpulimab as neoadjuvant treatment for HER2-low early or locally advanced breast cancer demonstrates manageable safety and potential for furtheroptimization. This warrants additional investigation to refine and optimize treatment strategies. Clinical trial information: NCT05726175 .

Compared with alteplase, recombinant human prourokinase (rhPro-UK)—a next-generation specific plasminogen activator—offers advantages such as weight-independent dosing and cost effectiveness. While a 35-mg dose of rhPro-UK has been recommended in previous randomized controlled trials (RCTs), its efficacy and safety profile have yet to be fully elucidated, as no relevant systematic reviews or meta-analyses have been conducted to date. This meta-analysis aimed to evaluate the safety and efficacy of 35 mg of rhPro-UK compared with those of control treatments, including 50 mg of rhPro-UK and alteplase monotherapy, in patients with acute ischemic stroke (AIS). Two independent reviewers systematically searched the PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov electronic databases up to May 24, 2025, to identify RCTs assessing the effects of 35 mg rhPro-UK versus control therapies in AIS patients. Study quality was assessed using the Cochrane RoB 2 tool. A random effects model was employed for the meta-analysis using Stata 18.0. Four RCTs involving 2412 patients were included. The 35-mg dose of rhPro-UK demonstrated comparable safety and efficacy to those of the other treatments. Notably, this dose was associated with the potential advantages of increasing early neurological recovery at 24 h (SMD = − 0.29, 95

AbstractBackgroundThis prospective real‐world study aimed to assess the efficacy and safety of eribulin in the clinical practice against advanced breast cancer (ABC) in China.Patients and MethodsIn this study, eligible patients with inoperable locally advanced or metastatic breast cancer who had experienced prior neo−/adjuvant or failed the palliative treatment with anthracycline/taxanes were included. Eribulin (1.4 mg/m2) was infused intravenously on Day 1 and Day 8 every 3 weeks until disease progression or intolerable toxicity occurred. The progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety of the treatment were assessed.ResultsOne hundred and thirty‐four patients were enrolled. The median PFS (mPFS) was 4.3 months (95% CI: 0.3–15.4). The ORR and DCR was 32.1% and 79.1%, respectively. The mPFS of patients who received eribulin as first‐ or second‐line treatment was significantly better than those who received eribulin as ≥3‐line treatment (6.9 months [95% CI: 3.2–8.8] vs. 4.0 months [95% CI: 3.4–4.6], p = 0.006). The mPFS of patients with triple‐negative, HER2‐positive, and HER2(−)/HR(+) was 3.4 (95% CI: 2.7–4.1), 6.2 (95% CI: 2.3–10.1) and 5.0 months (95% CI: 4.1–5.9), respectively. HER2(+) patients had significantly longer PFS than TNBC patients (p = 0.022). Patients received combination therapy had a significantly longer mPFS than those who received eribulin monotherapy (5.0 months [95% CI 3.6–6.3] vs. 4.0 months [95% CI: 3.3–4.7] [p = 0.016]). Multivariate analysis revealed that MBC patients with a molecular typing of non‐TNBC receiving eribulin as ≤2‐line therapy and combination therapy had a low risk of disease progression. Neutropenia (33.58%), leukopenia (11.94%), and thrombocytopenia (4.48%) were the most common treatment‐related adverse events.ConclusionEribulin demonstrated effective clinical activity and a favorable tolerability profile in Chinese patients with ABC in the real‐world. The efficacy and safety profile were consistent with those reported in previous randomized phase 3 trials.

Abstract Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been the most challenging subtype of BC, which consists of 20% of BC with an apparent correlation with poor prognosis. Despite that pyrotinib, a new HER2 inhibitor, has led to dramatic improvements in prognosis outcome, the efficacy of pyrotinib as monotherapy remain largely restricted due to its acquired resistance. Therefore, we aim at identifying a potent antitumor drug incorporated with pyrotinib for amplifying therapeutic efficacy for treating HER2-positive BC. Here, we reported a novel incorporation of pyrotinib in combination with chrysin, and explored its antitumor efficacy and the underlying mechanisms on HER2+ breast cancer. We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce apoptosis and inhibit BT-474 and SK-BR-3 tumor cells, and suppressed in vivo tumor growth in tumor-bearing mice models. This may be mechanistically attributed to the induction of enhanced endoplasmic reticulum stress to increase the autophagy level. Furthermore, it was demonstrated that the combined treatment with pyrotinib and chrysin induced ubiquitination and G6PD degradation by regulating zinc finger and BTB/POZ domain-containing family protein 16 (ZBTB16) in tumorigenesis of BC. Besides, we identified that miR-16-5p is a potential upstream regulatory target of ZBTB16. Blocking miR-16-5p overexpression could inhibit HER2-positive tumorigenesis and significantly potentiate the efficacy of pyrotinib in combination with chrysin. Together, these findings demonstrate the utility of combined treatment with pyrotinib and chrysin as a potential option in the target treatment of HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis. The miR-16-5p/ZBTB16/G6PD axis plays a crucial role in the pyrotinib plus chrysin-enabled anti HER2-positive BC Fig.1 a Cell viability of SK-BR-3 cells received various treatments. b Detection of cell cycle arrest of SK-BR-3 cells after various treatments. c Schematic diagram of the established protocol of the animal models. Photograph of resected tumor tissues, tumor volume (d), and tumor weight (e) of mice in different treatment groups during the whole testing period. f H&E, Ki67, and Tunel immunohistochemical staining of tumor sections of mice in various treatment groups. g Autophagy flux of SK-BR-3 cells labeled with mRFP-GFP-LC3 in the different treatment groups. h Expression level of ER stress markers in SK-BR-3 cells after various treatments via RT-qPCR and western blot. *P <0.05, compared with control group (DMSO), #P <0.05, compared with chrysin group, & P<0.05, compared with pyrotinib group. i Western blot analysis of the expression of G6PD in different treatment groups. j Fluorescence images of SK-BR-3 cells subjected to G6PD overexpression for the detection of autophagy level. k Ubibrowser database predicting the E3 ubiquitin ligases that may be involved in the regulation of G6PD ubiquitination. l Western blot analysis of G6PD protein half-life in SK-BR-3 cells with ZBTB16 silence. Cells were co-incubated with cycloheximide (CHX, 50μg/ml) for the indicated time. m Determination of the ubiquitination of G6PD in cells pretreated with 10 μM MG-132 for 3 h. Cells were transfected with ubiquitin after different treatments. The ubiquitinated G6PD was subjected to immunoprecipitation before western blot with ubiquitin antibody. n Dual-luciferase report verifying the targeting of ZBTB16 and miR-16-5p. o Transmission electron microscopy images of autophagosomes of tumors in various treatment groups (× 20000). p Immunohistochemical staining images of tumor slices for the determination of G6PD. q Schematic diagram for the underlying mechanism of pyrotinib combined chrysin against HER2-positive BC. Citation Format: Ting Luo, Xiaorong Zhong, Ping He, Dan Zheng, Yan Cheng, Kunrui Zhu. Combined Treatment with Pyrotinib and Chrysin Synergistically Improve the Autophagy Level in HER2-Positive Breast Cancer by Regulating the miR-16-5p/ZBTB16/G6PD Axis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-03.

PURPOSE:Endocrine therapy combined with ovarian function suppression (OFS) is recommended in intermediate- or high-risk patients among premenopausal women with hormone receptor-positive early breast cancer. However, in China, the cost-effectiveness of this strategy compared with endocrine therapy alone is unclear. This study aimed to evaluate the long-term cost-effectiveness of tamoxifen (TAM), TAM+OFS, and exemestane plus OFS (EXE+OFS).METHODS:On the basis of prognostic data from the Suppression of Ovarian Function Trial (SOFT), cost data from the Hospital Information System of the West China Hospital of Sichuan University, and health utility values from the published literature, a Markov model was established. The incremental cost-effectiveness ratio (ICER) was used to compare the treatment strategies.RESULTS:In a 25-year simulation of adjuvant therapy in Chinese women with early breast cancer, the total costs of TAM, TAM+OFS, and EXE+OFS were $7821, $9318, and $9445, respectively. The quality-adjusted life-years (QALYs) were 11.615, 11.896, and 11.734 years, respectively. Compared with TAM, the ICERs of TAM+OFS and EXE+OFS were $5,327.4021/QALY and $13,647.0588/QALY, respectively. The ICERs of TAM+OFS and EXE+OFS were below the threshold of $32,517/QALY. The reliability and stability of the simulation results were verified using Monte Carlo simulation and sensitivity analysis.CONCLUSION:In the context of limited resources in China, TAM+OFS and EXE+OFS are cost-effective options compared with TAM.

e13126 Background: Eribulin is a novel synthetic analog of halichondrin B that acts as a microtubule inhibitor and inhibits the G2-M growth phase. Eribulin was approved for metastatic breast cancer (MBC) based on the landmark phase 3 EMBRACE trial (Cortes et al, Lancet 2011; NCT00388726); however, only a small number of Asian patients were included in that trial. Therefore, in this real-world study, we retrospectively assessed the clinical outcomes of Chinese patients with MBC who received eribulin. Methods: Adult patients with MBC who received eribulin as several lines of therapy were retrospectively analyzed. Socio-demographic, clinical, pathology, imaging, and therapy records were reviewed. Progression-free survival (PFS) and tumor response were evaluated. Results: A total of 85 patients were included. The median age was 45 years (range, 21–63). Eribulin was used as a first, second, third, and fourth or more chemotherapy agent in 13 (15.3%), 16 (18.8%), 11 (12.9%) and 45 (52.9%) of patients with MBC, respectively. Eribulin was monotherapy in 32.9% of patients; eribulin plus anti-HER2 targeted therapy was used in 9.4% of patients; eribulin plus immunotherapy was used in 5.9% of patients; eribulin plus other chemotherapy was used in 36.5% of patients, and eribulin plus antiangiogenic therapy was used in 9.4% of patients. The objective response rate (ORR) was 28.2% overall. By number of lines of therapy, the first-line ORR was 38.5% and the second-line ORR was 37.5%. On subgroup analysis, ORR of patients with liver metastasis and lung metastasis was 43.9% and 38.6 %, respectively. By molecular classification, the ORR of patients with HR+/HER2− disease was 66.7%; among patients with HER2+ disease, 32.6%; and among patients with triple-negative BC, 13.3%. The 6-month PFS rate was 33.6% overall. By number of lines of therapy, the 6-month PFS rate among patients who received eribulin as first-line treatment was 67.7% and among patients who received eribulin as second-line treatment, 38.3%. Among patients who received eribulin monotherapy, the 6-month PFS rate was 21.4% and among patients who received eribulin combination therapy, 41.2%. No adverse reactions related to neutrophils were reported. Conclusions: This real-world retrospective study suggests that eribulin was effective in Chinese patients with MBC with a range of prior lines of chemotherapy, supporting the use of eribulin in the treatment of Chinese patients with MBC.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has been the most challenging subtype of BC, consisting of 20% of BC with an apparent correlation with poor prognosis. Despite that pyrotinib, a new HER2 inhibitor, has led to dramatic improvements in prognosis, the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance. Therefore, identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity. Here, we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC. We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest, inhibit the proliferation of BT-474 and SK-BR-3 BC cells, and repress in vivo tumor growth in xenograft mice models. This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress. Furthermore, the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase (G6PD) degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16 (ZBTB16) in tumorigenesis of BC. Mechanistically, we identified that miR-16-5p was a potential upstream regulator of ZBTB16, and it showed a significant inverse correlation with ZBTB16. Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC. Together, these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC). Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records. Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies. Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

Background: We report a case of hormone receptor (HR) positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer with multiple liver metastases who achieved good clinical benefit across cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy. Prior to this, the patient underwent neoadjuvant therapy and surgery as well as adjuvant endocrine therapy. We present and discuss three important treatment decision nodes associated with it. Case Description: A 60-year-old woman was diagnosed with invasive ductal carcinoma of the left breast (cT4bN2M0, stage IIIB, Luminal B HER2-negative type) at the West China Hospital of Sichuan University in 2020, and received neoadjuvant chemotherapy and modified radical mastectomy of the left breast from 2020 to 2021. Postoperative radiotherapy was performed in the left chest wall and left upper and lower clavicular region. Adjuvant therapy is anastrozole endocrine therapy. Multiple liver metastases developed in 2022. The pathological molecular typing of liver metastases was confirmed to be consistent with the primary lesion. In the context of primary endocrine resistance, the first-line treatment of choice was fulvestrant in combination with a targeted CDK4/6 inhibitor (abemaciclib). This combination regimen made the liver metastases visibly shrunk, leading to partial response (PR) and has achieved a progression-free survival of 12 months. And there were no serious drug-related adverse events during first-line treatment. Conclusions: CDK4/6 inhibitor is a promising antineoplastic agent for HR positive, HER2 negative breast cancer patients. With the development of research, the application scope of CDK4/6 inhibitors is gradually expanding, and the precision treatment of breast cancer requires more rational drug selection and combination.

Though single tumor immunotherapy and radiotherapy have significantly improved the survival rate of tumor patients, there are certain limitations in overcoming tumor metastasis, recurrence, and reducing side effects. Therefore, it is urgent to explore new tumor treatment methods. The new combination of radiotherapy and immunotherapy shows promise in improving therapeutic efficacy and reducing recurrence by enhancing the ability of the immune system to recognize and eradicate tumor cells, to overcome tumor immune tolerance mechanisms. Nanomaterials, as new drug-delivery-system materials of the 21st century, can maintain the activity of drugs, improve drug targeting, and reduce side effects in tumor immunotherapy. Additionally, nanomaterials, as radiosensitizers, have shown great potential in tumor radiotherapy due to their unique properties, such as light, heat, electromagnetic effects. Here, we review the mechanisms of tumor immunotherapy and radiotherapy and the synergy of radiotherapy with multiple types of immunotherapies, including immune checkpoint inhibitors (ICIs), tumor vaccines, adoptive cell therapy, and cytokine therapy. Finally, we propose the potential for nanomaterials in tumor radiotherapy and immunotherapy.

A 24-year-old woman had been initially treated for nonlactational mastitis at another hospital. The mass enlarged rapidly over 2 months despite undergoing anti-inflammatory treatment, incision, and drainage. Follow-up imaging and percutaneous biopsy revealed invasive ductal carcinoma, triple-negative type (cT4N2M0, Stage IIIB) (Fig 1).

Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and confer worse prognosis in breast cancer patients. The inhibitors targeting three key nodes of these pathways, PI3K, AKT and mTOR, are continuously developed. For breast cancer patients to truly benefit from PAM pathway inhibitors, it is necessary to clarify the frequency and mechanism of abnormal alterations in the PAM pathway in different breast cancer subtypes, and further explore reliable biomarkers to identify the appropriate population for precision therapy. Some PI3K and mTOR inhibitors have been approved by regulatory authorities for the treatment of specific breast cancer patient populations, and many new-generation PI3K/mTOR inhibitors and AKT isoform inhibitors have also been shown to have good prospects for cancer therapy. This review summarizes the changes in the PAM signaling pathway in different subtypes of breast cancer, and the latest research progress about the biomarkers and clinical application of PAM-targeted inhibitors.

OBJECTIVES:Due to the multidimensional, multilayered, and chronological order of the cancer data, it was challenging for us to extract treatment paths. To determine whether the cSPADE algorithm and system clustering proposed in this study can effectively identify the treatment pathways for early breast cancer.METHODS:We applied data mining technology to the electronic medical records of 6891 early breast cancer patients to mine treatment pathways. We provided a method of extracting data from EMR and performed three-stage mining: determining the treatment stage through the cSPADE algorithm → system clustering for treatment plan extraction → cSPADE mining sequence pattern for treatment. The Kolmogorov-Smirnov test and correlation analysis were used to cross-validate the sequence rules of early breast cancer treatment pathways.RESULTS:We unearthed 55 sequence rules for early breast cancer treatment, 3 preoperative neoadjuvant chemotherapy regimens, three postoperative chemotherapy regimens, and 2 chemotherapy regimens for patients without surgery. Through 5-fold cross-validation, Pearson and Spearman correlation tests were performed. At the significance level of p < 0.05, all correlation coefficients of support, confidence and lift were greater than 0.89. Using the Kolmogorov-Smirnov test, we found no significant differences between the sequence distributions.CONCLUSIONS:We have proved that cSPADE algorithm combined system clustering is an effective technique for identifying temporal relationships between treatment modalities, enabling hierarchical and vertical mining of breast cancer treatment models. In addition, we confirmed the robustness of the results by cross-validation of these treatment pathway ordering rules. Through this method, the treatment path of early breast cancer patients can be revealed, and the real-world breast cancer treatment behaviour model can be evaluated, which can provide reference for the redesign and optimization of treatment path.

Background Pathological complete response (pCR) is considered a surrogate endpoint for favorable survival in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Predictive biomarkers of treatment response are crucial for guiding treatment decisions. With the hypothesis that histological information on tumor biopsy images could predict NAC response in breast cancer, we proposed a novel deep learning (DL)-based biomarker that predicts pCR from images of hematoxylin and eosin (H&E)-stained tissue and evaluated its predictive performance. Methods In total, 540 breast cancer patients receiving standard NAC were enrolled. Based on H&E-stained images, DL methods were employed to automatically identify tumor epithelium and predict pCR by scoring the identified tumor epithelium to produce a histopathological biomarker, the pCR-score. The predictive performance of the pCR-score was assessed and compared with that of conventional biomarkers including stromal tumor-infiltrating lymphocytes (sTILs) and subtype. Results The pCR-score derived from H&E staining achieved an area under the curve (AUC) of 0.847 in predicting pCR directly, and achieved accuracy, F1 score, and AUC of 0.853, 0.503, and 0.822 processed by the logistic regression method, respectively, higher than either sTILs or subtype; a prediction model of pCR constructed by integrating sTILs, subtype and pCR-score yielded a mean AUC of 0.890, outperforming the baseline sTIL-subtype model by 0.051 (0.839, P = 0.001). Conclusion The DL-based pCR-score from histological images is predictive of pCR better than sTILs and subtype, and holds the great potentials for a more accurate stratification of patients for NAC.

A correction to this paper has been published: https://doi.org/10.1245/s10434-021-09771-9

Purpose: Histological image containing numerus tissue morphology information, is now the golden standard for breast cancer (BC) diagnosis, but it contributes little to prognosis in routine clinic practice. This study aims to assess the ability of pathology image for accurate prognostic prediction that might improve clinical decision making.Experimental Design: We used large-scale clinical datasets including 7,464 pathology images from 3,653 BC patients in three independent cohorts for pathological image-based model (PI model) establishment and independent testing. We trained a mask region-convolution neural network model to automatically label the nuclei in each tile sliced from WSIs. A total of 884 morphological features were distilled from each tile. The machine learning algorithm XGBoost was introduced to efficiently learn prognostic risk scores for PI model. Independent datasets from Hebei Province Cancer Hospital (HCH) and The Cancer Genome Atlas (TCGA) were used for testing.Results: For classification, the independent testing set of HCH could effectively differentiate cancerous from non-cancerous tiles with AUC at 0.947. For prognosis, independent testing set of TCGA showed good ability to differentiate high-risk patients from low-risk patients for overall survival (OS) in all the patients, and confirmed in each molecular subtypes and different AJCC stages (p<0.05, C-index ranges 0.60 to 0.69). Disease-Free Survival (DFS) prediction model also confirmed good performance ability (p<0.05, C-index ranges 0.61 to 0.73).Conclusions: Our data shows that deep mining of pathology image feature have good ability for BC prognosis prediction, which suggest potential applications for supporting clinical treatment decision making in the future.Funding Information: 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18012, ZYJC21035), and Science and Technology Department of Sichuan Province of China under Grant 2021YFS0236.Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This study was approved by the Ethics Committee of West China Hospital (reference number: 2021-764).

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer‐specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer‐specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer‐specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow‐up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer‐specific mortality (95% CI 0%‐65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer‐specific mortality (95% CI 11%‐82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%‐12%) reduction in cancer‐specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%‐39%). Our findings suggest that underinsured patients face a higher risk of breast cancer‐specific mortality in developing countries.