Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Expert consensus on the clinical application of immunotherapy in breast cancer: 2024.

Background: Significant progress has been made in immunotherapy of breast cancer (BC) with the approval of multiple immune checkpoint inhibitors (ICIs), particularly in early and metastatic triple-negative breast cancer (TNBC) settings. Most guidelines have recommended immune therapy as the important approach in BC, yet several critical aspects still require further clarification, including proper patient selection, treatment duration, optimized chemotherapy partner, predictive biomarkers, and specific considerations for Chinese patients. Methods: (I) Establishment of expert group: the expert group consists of 32 experts from departments such as medical oncology, breast surgery, and pathology; (II) literature search: mainly conducted in English databases (such as PubMed, Embase, and Cochrane Library) and Chinese databases (such as China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Database), with a search cutoff date of April 23, 2024; (III) assessment of evidence quality and recommendation strength: evidence quality and recommendation opinions are graded based on the evidence category and recommendation level of the Chinese Society of Clinical Oncology (CSCO) guidelines; (IV) consensus formulation: on the March 2, 2024, through online consensus meeting, the consensus content is thoroughly discussed, and opinions from all experts are solicited. Results: The consensus meeting has resulted in 15 detailed recommendations, providing clearer guidance on the clinical application of immunotherapy in BC management. The core suggestions are as follows: for early-stage II-III TNBC and metastatic TNBC (mTNBC) in the first-line setting, programmed cell death protein 1 (PD-1) inhibitors can be considered. However, for hormone receptor-positive/human epidermal growth factor receptor 2-negative BC (HR+/HER2- BC), HER2+ BC, and mTNBC in later lines of therapy, evidence is lacking to support the use of immunotherapy. Conclusions: This consensus provides a comprehensive overview of BC immunotherapy, including immunotherapy for early-stage BC and late-stage BC, immune related adverse event (irAE) management, biomarkers of immunotherapy, and future directions. The consensus consolidates these deliberations into 15 evidence-based recommendations, serving as a practical guide for clinicians to more scientifically and systematically manage the clinical application of immunotherapy.

A real-world comparison of circulating tumor cells in breast cancer from China: Novel device, CTC counts and its overall survival.

Background: Both CellSearch and CellCollector have been accepted as the proper devices to capture CTC by domestic approval department. However, there is little article about the comparison between these two devices around the world. Herein, we conducted the real-world study to compare with these two devices and to re-verify the efficacy of CTC counts. Methods: Patients who meet the following points should be included in the analysis. 1. Female, aged 18 years or older; 2. Eastern Cooperative Oncology Group (ECOG) score 0-2; 3. With at least one measurable tumor lesion; 4. Clear immunohistochemistry result; 5. Accept at least one CTC test. Patients were excluded in the analysis if they had a history of malignant tumors, incomplete follow-up information. Results: 536 metastatic breast cancer patients who had been detected for CTC at least once by CellSearch or CellCollector were included in the analysis. CellCollector in vivo CTC detection technology has a higher detection rate than the CellSearch system (69.2% vs 57.4%, P = 0.009). However, the proportion of CTC≥5 detected by CellSearch was higher than CellCollector (37.4% vs 16.3%, P < 0.001). There was a statistically significant difference in overall survival of patients with CTC negative and CTC positive (mOS:49.8 months vs 26.9 months). After 4 weeks of treatment, when CTC decreased by more than 50%, there was a significant difference in survival between the two groups (40.1 months vs 25.8 months, HR = 0.588, 95% CI: 0.350-0.933). In addition, for HER2-positive patients, Patients with CTC HER2 positive had longer overall survival than patients with CTC HER2 negative (median OS: 26.7 months vs 17.3 month, HR = 0.528, 95% CI: 0.269-0.887). Conclusions: Real-world data indicate that CTC is an independent prognostic factor, and CellCollector and CellSearch have their own advantages in CTC detection.

P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

Efficacy, Safety, and Population Pharmacokinetics of MW032 Compared With Denosumab for Solid Tumor-Related Bone Metastases: A Randomized, Double-Blind, Phase 3 Equivalence Trial.

Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.

Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial.

The combination of immune-checkpoint blockade with chemotherapy for the first-line treatment of advanced triple-negative breast cancer (TNBC) has generated mixed results. TORCHLIGHT is a randomized, double-blinded phase 3 trial evaluating the efficacy and safety of first-line toripalimab and nab-paclitaxel (nab-P) (n = 353; experimental arm) versus placebo and nab-P (n = 178; control arm) for the treatment of women with metastatic or recurrent TNBC. The primary end point was progression-free survival (PFS) assessed by a blinded independent central review in the PD-L1-positive and intention-to-treat populations. The secondary end points included overall survival and safety. Overall, 200 and 100 patients, in the toripalimab and placebo arm respectively had PD-L1-positive TNBC. At the prespecified interim analysis, a statistically significant improvement in PFS assessed by a blinded independent central review was demonstrated in the experimental arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470-0.906, P = 0.0102). The median overall survival was 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414-0.914, P = 0.0148). Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the experimental and control arms. The addition of toripalimab to nab-P provided a significant improvement in PFS for PD-L1-positive patients with metastatic or recurrent TNBC with an acceptable safety profile. ClinicalTrial.gov identifier NCT03777579 .

Antibody drug conjugates in breast cancer in China: Highlights, challenges, and prospects.

Antibody drug conjugates (ADCs) are novel drugs that exert specific cytotoxicity against tumor cells. China approved T-Dxd in May 2023, and their introduction has changed the nation's clinical practice. Although more than 700 ADCs are being investigated worldwide, the challenges that remain in antibody engineering, drug discovery, safety management, resistance, drug selection, and sequencing hinder the further promotion and application of ADCs. Experts in China have discussed the several critical concerns related to clinical practice since 2022. Here, the authors conducted a review of ADCs and then discussed several ADCs explored in China. This study proposes several solutions and strategies to maximize the potential benefit that ADCs can provide to patients with breast cancer.

Electroacupuncture for post-stroke urinary incontinence: a systematic review and meta-analysis with trial sequential analysis.

Background: The evidence for the effectiveness of electroacupuncture (EA) for post-stroke urinary incontinence (PSUI) patients remains unclear. Therefore, the purpose of this systematic review and meta-analysis was to assess the efficacy of EA for PSUI. Methods and analysis: Eight English and Chinese databases were searched from their inception until 1 August 2023 to collect randomized controlled trials (RCTs) that investigated the effect of EA on PSUI. Two reviewers independently selected studies that met the eligibility criteria, extracted the necessary data, and assessed the risk of bias for included studies using Cochrane Handbook version 5.1.0. Meta-analysis was performed using Review Manager software (version 5.4.1). Publication bias detection was conducted using STATA (version 16.0). Sequential analysis was performed using TSA 0.9.5.10 Beta. The Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) was used for assessing the certainty of evidence. Results: We included 15 RCTs involving a total of 1,414 patients. The narrative analysis revealed that compared with sham EA, genuine EA exhibited greater efficacy in reducing occurrences of 24-h urinary incontinence while also enhancing maximum cystometric capacity (MCC). Moreover, this effect remained significant even during the 3-month follow-up period. Fourteen studies were encompassed within the quantitative analysis. In contrast to active interventions, EA did not yield an improvement in the responder rate (RR 1.53, 95% CI 0.61 to 3.80, p = 0.36). When compared with basic treatments, the combination of EA with them led to a reduction in 24-h urinary incontinence occurrences (MD -0.56, 95% CI -0.60 to -0.52, p < 0.00001), an improvement in MCC (MD 43.23, 95% CI 28.86 to 57.60, p < 0.00001), and a decrease in residual urine volume (RUV; MD -19.99, 95% CI -29.75 to -10.23, p < 0.0001). However, it did not lead to an increase in the responder rate (RR 1.39, 95% CI 0.88 to 2.20, p = 0.16). In comparison to basic treatments combined with active interventions, the amalgamation of EA and them led to an increase in the responder rate (RR 1.24, 95% CI 1.14 to 1.35, p < 0.00001), a reduction in 24-h urinary incontinence occurrences (MD -2.90, 95% CI -5.26 to -0.55, p = 0.02), a decrease in International Consultation on Incontinence Questionnaire-Short Form scores, and an improvement in both MCC (MD 42.11, 95% CI 23.26 to 60.96, p < 0.0001) and RUV (MD 42.11, 95% CI 23.26 to 60.96, p < 0.0001). Furthermore, all reported adverse effects associated with EA were mild. The trial sequential analysis suggested that a sufficient sample size was available to yield results. However, the level of evidence was predominantly assessed as low or very low. Conclusion: Electroacupuncture improved post-stroke urinary incontinence with no serious adverse effects. Caution is warranted due to methodological issues, and more high-quality studies are required to confirm its efficacy and safety.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023449599, Identifier CRD42023449599.

Safety of COVID-19 Vaccination in Patients With Breast Cancer: Cross-Sectional Study in China.

BACKGROUND: The widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce. OBJECTIVE: This study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer. METHODS: Patients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients. RESULTS: A total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs. CONCLUSIONS: Compared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882.

Auricular acupressure for constipation in adults: a systematic review and meta-analysis.

Introduction: Auricular acupressure (AA) has been widely utilized in the management of constipation, with several studies suggesting its efficacy in treating constipation patients. However, the safety and effectiveness of AA in constipation remain uncertain. Hence, the aim of this study was to assess the effectiveness and safety of AA for constipation. Methods and analysis: A total of eight electronic databases and three clinical trial registration platforms were searched from their inception to April 2023 for randomized controlled trials (RCTs) of AA for constipation. The included studies were appraised for quality using the Cochrane Collaboration's Risk of Bias Assessment tool. The quality of evidence was assessed by two independent reviewers employing the Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) evaluation tool. Meta-analysis of data and assessment of publication bias were performed using RevMan 5.4 and STATA 13.0 software, respectively. Results: This review included 34 randomized controlled trials conducted between 2007 and 2023, involving 2,465 participants. The findings of the study indicate that overall, AA is significantly associated with improved CSBMs (MD = 1.22, 95% CI [0.68, 1.77], p < 0.0001, I2 = 0%), BSF (MD = 0.72, 95%CI: [0.15,1.28], p = 0.01, I2 = 82%), CAS (MD = -3.28, 95%CI: [-5.95, -0.60], p = 0.02, I2 = 80%), responder rate (RR = 1.27, 95%CI: [1.16, 1.38], p < 0.00001, I2 = 79%), cure rate (RR = 1.84, 95% CI [1.56, 2.15], p < 0.00001, I2 = 0%), and PAC-QOL (MD = -2.73, 95% CI: [-3.41, -2.04], p < 0.00001, I2 = 98%) compared to the control group. However, no difference in PAC-SYM (MD = -0.15, 95%CI: [-0.38,0.07], p = 0.19, I2 = 67%) was found between the two groups. Additionally, there was no significant difference in adverse events (RR = 0.53, 95% CI: [0.24, 1.21], p = 0.13, I2 = 38%). Conclusion: Based on the available evidence, auricular acupressure appears to be a potentially safe and effective intervention for managing constipation in adults. Nonetheless, the overall quality of evidence for the identified outcomes was assessed as low to very low, highlighting the need for additional high-quality randomized controlled trials to further validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023425033.

Trends in Disparities and Transitions of Treatment in Patients With Early Breast Cancer in China and the US, 2011 to 2021.

Importance: Breast cancer treatment has profoundly improved in China recently. However, trends in disparities and transitions of treatment in early-stage cancer between China and the US are not well known. Objective: To identify changes for patients with early breast cancer by using large databases from China and the US. Design, Setting, and Participants: This multicenter cross-sectional study used the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) database from hospitals in 13 provinces in China and the Flatiron Health (hereinafter referred to as Flatiron) database from more than 280 community oncology clinics in the US. Patients with stage I to III breast cancer diagnosed from January 1, 2011, to December 31, 2021, were included. Data were analyzed from June 10 to December 1, 2022. Main Outcomes and Measures: The distribution of age, clinical stage, and cancer subtypes at diagnosis were examined overall and by year. The mean annual percent change (MAPC) from 2011 to 2021 in systemic therapy and surgery was also analyzed. Results: A total of 57 720 patients with early breast cancer were screened from the CSCO BC (n = 45 970) and Flatiron (n = 11 750) databases. The median age at diagnosis in China among the 41 449 patients included in the age analysis was 47 (IQR, 40-56) years; in the US, the median age was 64 (IQR, 54-73) years. Among patients with clinical stage data in the CSCO BC (n = 22 794) and Flatiron (n = 4413) databases, the proportion of stage I cancer was 7250 (31.8%) vs 2409 (54.6%); stage II cancer, 10 043 (44.1%) vs 1481 (33.6%); and stage III cancer, 5501 (24.1%) vs 523 (11.9%). The proportion of hormone receptor-positive cancer in China was 69.8%, lower than that in the US (87.5%). For patients with ERBB2 (formerly HER2 or HER2/neu)-positive cancer, the proportion in China (30.2%) was higher than that in the US (15.6%). For neoadjuvant therapy, the annual rate increased from 247 of 1553 (15.9%) to 200 of 790 (25.3%) in China, with an MAPC of -4.4% (95% CI, -50.6% to 85.0%; P = .89). For patients with ERBB2-positive cancer, the proportion treated with trastuzumab in early-stage cancer in China increased significantly, with an MAPC of 22.1% (95% CI, 17.4%-26.9%; P < .001), and overtook that in the Flatiron database since 2017 (1684 [68.5%] vs 550 [62.5%]; P < .001). Conclusions and Relevance: The findings of this cross-sectional study suggest that disparities in treatment of early breast cancer narrowed between China and the US during the study period. The rapid growth of trastuzumab treatment in China was suggestive of differential access to targeted ERBB2 therapy.

Phase III study of HR-positive/HER2-negative/lymph node-positive breast cancer non-responsive to primary chemotherapy: a randomized trial.

There are few studies focus on post-neoadjuvant treatment in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-positive (LN+) breast cancer, a multi-center, open-label, randomized, controlled phase III trial was conducted to evaluate pathological response-guided non-cross-resistant adjuvant chemotherapy in patients with HR+/HER2-/LN+ breast cancer who were non-responsive to primary chemotherapy. Patients received four cycles of non-cross-resistant adjuvant chemotherapy plus endocrine therapy (ET), or ET alone. Forty patients responsive to neoadjuvant chemotherapy and with Miller and Payne G4 or G5 and LN- status were assigned to the observation group. Distant disease-free survival was the primary endpoint. The final intention-to-treat analysis comprised 379 patients. After a median follow-up period of 72.4 months, the 5-year distant disease-free survival was 92% and 90% in the chemotherapy plus ET and ET-alone groups, respectively. Comparatively, the observation group showed a trend towards better distant disease-free survival. For patients non-responsive to neoadjuvant chemotherapy, adjuvant non-cross-resistant chemotherapy did not significantly improve distant disease-free survival compared to ET alone.

Assessing the decision quality of artificial intelligence and oncologists of different experience in different regions in breast cancer treatment.

Background: AI-based clinical decision support system (CDSS) has important prospects in overcoming the current informational challenges that cancer diseases faced, promoting the homogeneous development of standardized treatment among different geographical regions, and reforming the medical model. However, there are still a lack of relevant indicators to comprehensively assess its decision-making quality and clinical impact, which greatly limits the development of its clinical research and clinical application. This study aims to develop and application an assessment system that can comprehensively assess the decision-making quality and clinical impacts of physicians and CDSS. Methods: Enrolled adjuvant treatment decision stage early breast cancer cases were randomly assigned to different decision-making physician panels (each panel consisted of three different seniority physicians in different grades hospitals), each physician made an independent "Initial Decision" and then reviewed the CDSS report online and made a "Final Decision". In addition, the CDSS and guideline expert groups independently review all cases and generate "CDSS Recommendations" and "Guideline Recommendations" respectively. Based on the design framework, a multi-level multi-indicator system including "Decision Concordance", "Calibrated Concordance", " Decision Concordance with High-level Physician", "Consensus Rate", "Decision Stability", "Guideline Conformity", and "Calibrated Conformity" were constructed. Results: 531 cases containing 2124 decision points were enrolled; 27 different seniority physicians from 10 different grades hospitals have generated 6372 decision opinions before and after referring to the "CDSS Recommendations" report respectively. Overall, the calibrated decision concordance was significantly higher for CDSS and provincial-senior physicians (80.9%) than other physicians. At the same time, CDSS has a higher " decision concordance with high-level physician" (76.3%-91.5%) than all physicians. The CDSS had significantly higher guideline conformity than all decision-making physicians and less internal variation, with an overall guideline conformity variance of 17.5% (97.5% vs. 80.0%), a standard deviation variance of 6.6% (1.3% vs. 7.9%), and a mean difference variance of 7.8% (1.5% vs. 9.3%). In addition, provincial-middle seniority physicians had the highest decision stability (54.5%). The overall consensus rate among physicians was 64.2%. Conclusions: There are significant internal variation in the standardization treatment level of different seniority physicians in different geographical regions in the adjuvant treatment of early breast cancer. CDSS has a higher standardization treatment level than all physicians and has the potential to provide immediate decision support to physicians and have a positive impact on standardizing physicians' treatment behaviors.

Efficacy relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy.

PURPOSE: Breast cancer has become the leading cause of cancer mortality in women. Although immune checkpoint inhibitors targeting programmed death-1 (PD-1) are promising, it remains unclear whether PD-L1 expression on circulating tumor cells (CTCs) has predictive and prognostic values in predicting and stratifying metastatic breast cancer (MBC) patients who can benefit from anti-PD-1 immunotherapy. METHODS: Twenty six MBC patients that received anti-PD-1 immunotherapy were enrolled in this study. The peptide-based Pep@MNPs method was used to isolate and enumerate CTCs from 2.0 ml of peripheral venous blood. The expression of PD-L1 on CTCs was evaluated by an established immunoscoring system categorizing into four classes (negative, low, medium, and high). RESULTS: Our data showed that 92.3% (24/26) of patients had CTCs, 83.3% (20/26) of patients had PD-L1-positive CTCs, and 65.4% (17/26) of patients had PD-L1-high CTCs. We revealed that the clinical benefit rate (CBR) of patients with a cut-off value of ≥ 35% PD-L1-high CTCs (66.6%) was higher than the others (29.4%). We indicated that PD-L1 expression on CTCs from MBC patients treated with anti-PD-1 monotherapy was dynamic. We demonstrated that MBC patients with a cut-off value of ≥ 35% PD-L1-high CTCs had longer PFS (P = 0.033) and OS (P = 0.00058) compared with patients with a cut-off value of < 35% PD-L1-high CTCs. CONCLUSION: Our findings suggested that PD-L1 expression on CTCs could predict the therapeutic response and clinical outcomes, providing a valuable predictive and prognostic biomarker for patients treated with anti-PD-1 immunotherapy.

Novel Anti-HER2 Antibody-Drug Conjugates Versus T-DM1 for HER2-Positive Metastatic Breast Cancer After Tyrosine Kinase Inhibitors Treatment.

BACKGROUND: Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure. MATERIALS AND METHODS: HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety. RESULTS: A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group. CONCLUSIONS: In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.

A comparison between clinical decision support system and clinicians in breast cancer.

Objective: We are building a clinical decision support system (CSCO AI) for breast cancer patients to improve the efficiency of clinical decision-making. We aimed to assess cancer treatment regimens given by CSCO AI and different levels of clinicians. Methods: 400 breast cancer patients were screened from the CSCO database. Clinicians with similar levels were randomly assigned one of the volumes (200 cases). CSCO AI was asked to assess all cases. Three reviewers were independently asked to evaluate the regimens from clinicians and CSCO AI. Regimens were masked before evaluation. The primary outcome was the proportion of high-level conformity (HLC). Results: The overall concordance between clinicians and CSCO AI was 73.9% (3621/4900). It was 78.8% (2757/3500) in the early-stage, higher than that in the metastatic stage (61.7% [864/1400], p < 0.001). The concordance was 90.7% (635/700) and 56.4% (395/700) in adjuvant radiotherapy and second-line therapy respectively. HLC in CSCO AI was 95.8% (95%CI:94.0%-97.6%), significantly higher than that in clinicians (90.8%, 95%CI:89.8%-91.8%). Considering professions, the HLC of surgeons was 85.9%, lower than that of CSCO AI (OR = 0.25,95%CI: 0.16-0.41). The most significant difference in HLC was in first-line therapy (OR = 0.06, 95%CI:0.01-0.41). When clinicians were divided according to their levels, there was no statistical significance between CSCO AI and higher level clinicians. Conclusions: Decision from CSCO AI for breast cancer was superior than most clinicians did except in second-line therapy. The improvements in process outcomes suggest that CSCO AI can be widely used in clinical practice.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer.

BACKGROUND: Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC. METHODS: Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS. CONCLUSIONS: ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.