Cancer immunotherapy is increasingly moving toward personalized, precision-based strategies, with cancer vaccines emerging as a promising approach to reshape treatment. However, despite their potential, current tumor vaccines often yield limited clinical responses and subpar immunogenicity, underscoring the urgent need for innovative delivery systems to enhance immune activation. Bacterial outer membrane vesicles (OMVs), which possess natural immunomodulatory properties and impressive engineering flexibility, have attracted attention as versatile platforms for vaccine development and bioengineering applications. This review thoroughly summarizes recent advances in using OMVs to enhance the effectiveness of cancer vaccines. First, we explain the key biological features of OMVs that support their immunotherapeutic potential. Next, we carefully analyze the primary mechanisms by which OMVs enhance immune responses, as well as cutting-edge engineering strategies to improve their safety, immunogenicity, and specificity. Additionally, we discuss the significant challenges that hinder the clinical use of OMV-based cancer vaccines and provide a comprehensive review of current progress and future outlooks. Looking forward, combining artificial intelligence, tumor microenvironment profiling, and neoantigen discovery is expected to drive the development of next-generation, personalized OMV-based immunotherapies. Overall, OMVs stand out as a transformative platform capable of overcoming major obstacles in cancer vaccine development and pushing forward future cancer immunotherapy.

To the Editor: In the last decade, neoadjuvant chemotherapy (NAC) has become a well-accepted treatment option for breast cancer, although few detailed description of NAC in China has yet been reported.[1] A previous study found that among patients with clinically node-negative (cN0) breast cancer, 97.7% (432/442) with breast pathologic complete response (bpCR) had ypN0 (absence of metastases in the axillary lymph nodes); and 71.6% (882/1232) without bpCR achieved ypN0 (P <0.001). As for human epidermal growth factor receptor 2 (HER2) positive or triple-negative breast cancer (TNBC) that achieved bpCR, the probability of lymph node metastasis was less than 2%. This research aimed to investigate NAC status in China using data obtained from the Chinese Society of Breast Surgery (CSBrS) study from 2010 to 2020. It seeks to answer the following questions: what the current trend in NAC utilization is and what the effects of breast and axillary lymph node are in China. Data were obtained from 20 hospitals in China by CSBrS study (analyzed the data from January 1, 2010 to December 31, 2020). This study was approved by the Ethics Committee of the First Hospital of Jilin University (No. 2021-066). This clinical study was a retrospective study, the application for exemption of informed consent was submitted, and the exemption was approved. Data collection and exclusion criteria are provided in Supplementary Figure 1, https://links.lww.com/CM9/B719. bpCR was defined as the absence of both invasive and cancer in situ within the breast, and ypN0 defined as the absence of metastasis within the axillary lymph nodes after NAC. Isolated tumor cell (ITC) was defined as ypN positive. Patients were defined as cN0 prior to NAC if imaging examination and/or lymph node(s) biopsy showed no evidence of metastasis. Patients were defined as cN1 if the axillary lymph node biopsy confirmed nodal involvement and/or the lymph node(s) were movable at palpation. General information regarding clinical and pathologic patient data was evaluated. Data were presented as numbers and percentages. Proportions were compared between groups by χ2 analysis. SPSS (version 22.0; IBM Corp., Chicago, IL, USA) and Prism 9 (GraphPad Software, San Diego, CA, USA) were used for statistical analysis. All statistical tests were based on a two-sided probability, and P <0.001was considered statistically significant. A total of 11,108 patients scheduled NAC, and 10,713 patients were deemed to be eligible and were included in the final analysis. Demographics and clinical characteristics of enrolled patients are provided in Supplementary Table 1, https://links.lww.com/CM9/B719; and initial chemotherapy regimen information is provided in Supplementary Table 2, https://links.lww.com/CM9/B719. The overall usage rate for NAC increased from 9.3% in 2010 to 16.2% in 2020 [Supplementary Figure 2, https://links.lww.com/CM9/B719]. The NAC rate differed across hospitals, with the lowest rate being 3.8% and the highest being 36.4% in 2020. For HER2+ breast cancer patients, the use of targeted therapy increased annually, with the usage rate reaching 65.1% in 2020 [Supplementary Figure 3A, https://links.lww.com/CM9/B719]. The percentage of patients who underwent breast-conserving surgery, axillary lymph node biopsy, and sentinel lymph node biopsy (SLNB) increased annually [Supplementary Figure 3B–D, https://links.lww.com/CM9/B719]. Based on the subtype analysis, the rates of bpCR were 5.8% (52/904), 13.3% (449/3386), 22.1% (486/2201), 31.9% (509/1596), and 30.4% (499/1644) for luminal A, luminal B, hormone receptor (HR)+/HER2–, HR–/HER2+, and TNBC, respectively [Supplementary Table 3, https://links.lww.com/CM9/B719]. In this study, 15.3% (1567/10,254) had total pathologic complete response (pCR) in both breast and lymph nodes, and 30.1% (3086/10,254) had axillary pathologic complete response (apCR) with residual tumor in breast; and 5.0% (511/10,254) had bpCR with positive lymph node metastasis. A total of 6142 patients with cT1-2N0-1 breast cancer were included for the association of bpCR with the absence of axillary lymph node metastasis. A higher proportion of ypN0 was found among cT1-2N0 patients with bpCR than among their counterparts (100.0% [8/8] vs. 60.5% [107/177] for luminal A, P = 0.025 85.3% [93/109] vs. 58.4% [353/604] for luminal B, P <0.001; 90.6% [126/139] vs. 72.8% [249/342] for HR+/HER2+, P <0.001; 94.5% [103/109] vs. 78.5% [153/195] for HR–/HER2+, P <0.001; and 93.7% [133/142] vs. 80.2% [223/278] for TNBC, P <0.001) [Supplementary Table 4, https://links.lww.com/CM9/B719]. Overall, for patients with cT1-2N0 cancer, the proportion with ypN0 was 91.3% (463/507) with bpCR, while the proportion was 68.0% (1085/1596) for patients without bpCR (P <0.001). Among the patients with cT1-2N1 who achieved bpCR, 47.4% (9/19) of luminal A patients were free from lymph node involvement; 62.4% (138/221) for luminal B; 72.3% (146/202) for HR+/HER2+; 80.0% (180/225) for HR–/HER2+; and 74.6% (205/872) for TNBC [Supplementary Table 4, https://links.lww.com/CM9/B719]. Overall, for these patients, 71.8% (626/872) with bpCR achieved ypN0; and 31.9% (1010/3167) without bpCR achieved ypN0 (P <0.001). As shown in Supplementary Table 5, https://links.lww.com/CM9/B719, among the 872 bpCR patients (cT1-2N1), 246 had lymph node metastasis after NAC, 64.6% (159/246) had ypN1, and 35.4% (87/246) had ypN2–3 metastasis. For HR–/HER2+ and TNBC cancer, only 4.4% and 10.2% patients had more than three metastatic lymph nodes. In this multicenter retrospective cohort study, we found that the overall usage rate of NAC for breast cancer in China has increased within the last decade, although the rate varies greatly due to region, hospital, or the attitudes of patients and doctors. In this study, the proportion of targeted drugs used is 40.5%.Although the rate is not as high as that used in clinical trials, it is still higher than that in the study of Li et al[2] (32.5%) from China, CSBrS-006. Axillary status after NAC has been consistently reported as a robust prognostic factor for patient survival independent of primary tumor response. We sought to answer whether a pathologic primary tumor response to NAC could predict axillary lymph node status.[1,3] Among the patients with cT1-2N0 breast cancer who achieved bpCR post-NAC, over 90.0% of the patients had no residual nodes, particularly among those with HR–/HER2+ or TNBC patients. Among those with cN1 breast cancer, more patients had residual cancer in the lymph nodes regardless of whether bpCR was achieved. According to the consensus of the 2017 St. Gallen International Expert Meeting, for patients with stage cN0 disease who receive NAC, SLNB is safe and recommended after NAC.[4] The GANEA2 study[5] also confirmed the accuracy and safety of SNLB after NAC for breast cancer patients. For cN0 patients, apCR was strongly related to the breast cancer subtypes. apCR rates were 93.3%, 98.4%, 100%, and 98.5% for HR+/HER2–, HR+/HER2+, HR–/HER2+, and TNBC patients, respectively. Barron et al[3]. found that the rates of ypN0 for patients with cN0 HER2+ or TNBC breast cancer, who achieved bpCR after NAC, were 99.0% and 98.4%, respectively. In this study, patients with cN0 HR–/HER2+ cancer or TNBC who achieved bpCR after NAC had ypN0 rates of 94.5% and 93.7%, respectively. For TNBC and HR–/HER2+ patients with cN0, our results indicate that it may be safe to implement SLNB instead of ALND after NAC. Since the ypN0 rates of these patients are high, it may also be feasible for cN0, bpCR, and HR-/Her2+,TNBC patients to omit SLNB. CSBrS initiated this multicenter retrospective study to further confirm whether this is a universal phenomenon that does exist in the real world. However, more clinical data are required for follow-up safety verification. Caution is necessary for patients with cT1-2N1, treated with SLNB and with axillary lymph node degeneration after NAC. It is necessary to use dual tracers for the detection of ≥3 sentinel lymph nodes (SLNs), and the placement of marker clips for the identification of positive lymph nodes before NAC, as well as markers removal during surgery.[7] The ACOSOG Z1071 trial found that after double marker identification, ≥3 SLNs reduced the false negative rate to 9.8%. In the GANEA2 study[5], for patients with initially involved lymph nodes who had negative SLNs after NAC, in the absence of lymph vascular invasion, and given a remaining breast tumor size of less than 5 mm, the risk for a positive ALND was 3.7%, regardless of the number of SLNs that were removed. Barrio et al[8] found that among 610 patients, 555 (91%) cN1 improved to cN0 after NAC and underwent SLNB. The results demonstrated cN1 patients with three or more negative SLNs and nodal radiation, although without routine nodal clipping, nodal recurrence rates were low. These findings support the possibility of omission of ALND for such patients. In this study, for all subtypes of breast cancer, the number of axillary lymph node metastases gradually decreased as the number of positive nodes increased [Supplementary Table 5, https://links.lww.com/CM9/B719]. For patients with HR–/HER2+ and TNBC cancer, the proportions with four or more axillary lymph node metastases were 4.4% and 10.2%, respectively.[1,6] Combined with the conclusions of previous studies, for patients with cN1, HR-/HER2+, TNBC, and bpCR, as well as negative SLN patients, avoidance of ALND is acceptable. Since the proportion of patients with more than four positive SLNs is very low, the use of radiotherapy instead of ALND is likely safe for certain types of breast cancer patients. However, the results of the Alliance A011202 trial, more clinical data, and further prospective studies are necessary to ensure the accuracy of this conclusion. This study provides representative data for the treatment of women with breast cancer in real world China, which provides for increased generalization of the findings. However, it is important to note that axillary lymph node aspiration was not performed in some patients who received cN1 imaging assessment, which may affect pre-neoadjuvant N staging. With a decreasing number of contra-indications, the use of NAC in China has increased yearly. The rates of cT1-2N0, TNBC, and HR–/HER2+ patients with ypN0 were found to be very high. More prospective studies are needed to demonstrate whether these patients can be exempted from SLNB. Acknowledgments The authors acknowledge the member units of CSBrS for the data collection, Yangyu Zhang for the data analysis and Xiaoyun Mao for providing revisions to this manuscript. We thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript. Funding This work was supported by a grant from the Beijing Medical Reward Foundation (No. YXJL-2016-0040-0012). Conflicts of interest None.

Background:The axillary lymph node positive (ypN+) rate in patients with clinically node-negative (cN0) breast cancer who have achieved breast pathologic complete response (bpCR) after neoadjuvant systemic therapy (NST) is extremely low, and this population has the potential to be exempt from sentinel lymph node biopsy (SLNB). However, an overview of the ypN+ rate in this population for different breast cancer subtypes is lacking.Objective:To provide the pooled ypN+ rate in cN0 patients who achieved bpCR after NST in different breast cancer subtypes defined by hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status.Methods:A systematic literature search was conducted in Embase and PubMed on July 20, 2022. Two authors independently selected studies that met the inclusion criteria and extracted all data. The pooled ypN+ rates for each subtype were calculated by a random-effects model using the Stata 16.0 metaprop command.Results:The pooled analysis of 9609 cN0 patients who achieved bpCR showed that the ypN+ rate was lowest for the HR+/HER2+ (0%) subtype, followed by HR+/HER2- (5.1%), HR-/HER2+ (0.6%), and HR-/HER2- (0.3%). Additionally, 6571 cT1-T2N0 patients who achieved bpCR had a pooled ypN+ rate of 0.6%, and the ypN+ rates for different subtypes were as follows: HR+/HER2+ (1.7%), HR+/HER2- (2.7%), HR-/HER2+ (0.1%), and HR-/HER2- (0.8%).Conclusion:Our results suggested that cN0 patients who achieve bpCR may be exempt from axillary surgery in the HR+/HER2-, HR+/HER2+, and HR-/HER2- subtypes because of the extremely low probability of residual axillary lymph node disease. However, the safety of omitting axillary surgery needs to be further confirmed by prospective studies.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022351739.

乳腺癌作为全球女性发病率最高的癌症,其研究进展被广泛关注,不断累积的基础研究成果为争取更早发现,更精准治疗,更优化预后提供了理论基础.乳腺癌细胞在发生和发展过程中出现代谢重编程,其改变的范围和功能因乳腺癌亚型而异,同时癌细胞与周围复杂微环境发生相互作用,代谢与微环境的改变又进一步影响肿瘤药物治疗效果和远处转移.

In early 2020, 2019 novel coronavirus disease (known as COVID-19) broke out and became a public health emergency of international concern. COVID-19 spread around the whole world in a short time because of the various transmission routes (such as droplets, contact, aerosol and other means) and long incubation period (1). Jilin Province (a province in northeastern China) launched the first-level response to major public health emergencies rapidly on January 25th, 2020. Since health care workers and hospitals are at high risk of infection, we could see many changes made in medical industry after the breakout of COVID-19. In the First Hospital of Jilin University, we pretested triage of fever patients to identify suspected cases at the first time and admitted reservation registration only through the internet. In respond to COVID-19, experts of different areas also updated guidelines for different diseases. According to Liang’s research (2), cancer patients seems to be more suspicious to COVID-19 in China. Breast cancer is known as the most common cancer among women. To combat COVID-19 and find optimal ways of diagnosis and treatment under the epidemic situation, professors in our Department of Breast Surgery in the First Hospital of Jilin University made some adjustment towards the management of breast cancer according to the new rules of our hospital and guidelines of breast cancer during the outbreak of COVID-19. We present the following article in accordance with the Original Article

A mapping technique was used in the present study to explore the biological and imaging characteristics of invasive breast cancer and normal breast tissues in Raman examination data and construct a diagnostic model for breast cancer. Raman examination data reflect the biochemical or molecular characteristics of the target tissues. A total of 45 specimens from patients with breast cancer who underwent surgery and 25 adjacent normal breast tissue specimens were included in the present study. Using the specimens, a total of 53 sets of mapping data and 2,597 pieces of Raman spectral data were obtained. The collected spectra were corrected and fitted, the Raman spectra were analyzed by robust statistical methods, and a diagnostic model was constructed using the k-Nearest Neighbor (KNN) method. The KNN classification method was applied to analyze the characteristics of the mapping test application. The percentage of outliers in the mapping data for malignant and normal breast tissues was 12.7 and 6.6%, respectively. The percentage of outlier data in the conventional single-point detection data for malignant and normal breast tissues was 24.5 and 26.0%, respectively. Analysis using a t-test identified a significant difference in the number of outliers between mapping and single-point detection for malignant (t=-6.169; P<0.001) and normal breast tissues (t=-8.873; P<0.001). Based on the mapping data, the accuracy, sensitivity and specificity for breast cancer detection by the diagnostic model constructed using the KNN method was 99.56, 96.6 and 98.48%, respectively. The positive and negative predictive value of this model was 99.56 and 89.04%, respectively. The data obtained by mapping technology demonstrated improved stability and contained less outliers compared with single-point detection. The diagnostic model constructed using the mapping data demonstrated excellent diagnostic performance and good correspondence with pathological results. The findings of the present study demonstrated the feasibility of the application of the diagnostic model for intraoperative real-time imaging for patients with breast cancer. This study provided the foundation of Raman spectroscopy-based diagnostic imaging at the molecular level.

BACKGROUND:Postoperative endocrine therapy is known to reduce recurrence and mortality in patients with estrogen receptor (ER)- or progestogen receptor (PR)-positive breast cancer. Correlates and determinants of compliance with endocrine therapy among Chinese patients with breast cancer are not known. The aim of this study was to elucidate the efficacy and adherence of endocrine therapy in China and suggest effective improvements on the adherence.PATIENTS AND METHODS:We analyzed the survival of 1,110 patients eligible for endocrine therapy and adherence of 699 patients to endocrine therapy. Kaplan-Meier curves, log-rank tests and Cox proportional hazard models were used to evaluate survival, and logistic regression models were used to assess variables associated with treatment adherence.RESULTS:Long-term endocrine therapy was associated with lower recurrence rate (HR 0.72; 95% CI 0.56-0.93; p=0.013). Adherence to endocrine therapy was only 63.1%. Sociodemographic characteristics of patients, clinical- and medication-related characteristics and patients' attitudes were associated with adherence to endocrine therapy.CONCLUSION:Adherence to endocrine therapy in Chinese patients with ER+/PR+ breast cancer was <65%. Both patients and physicians should take progressive steps to improve the rate of adherence.

Backgrounds Tamoxifen is typically used to treat patients with estrogen receptor alpha (ERα)-positive breast cancer. However, 30% of these patients gain acquired resistance to tamoxifen during or after tamoxifen treatment. As a Ras modulator, Nogo-B receptor (NgBR) is required for tumorigenesis through the signaling crosstalk with epidermal growth factor (EGF) receptor (EGFR)-mediated pathways. NgBR is highly expressed in many types of cancer cells and regulates the sensitivity of hepatocellular carcinoma to chemotherapy. In this study, we found the expression of NgBR is increased in tamoxifen-resistant ERα-positive breast cancer cells. Methods Tamoxifen-resistant ERα-positive MCF-7 and T47D breast cancer cell lines were established by culturing with gradually increased concentration of 4-hydroxytamoxifen (4-OHT). The effects of NgBR on tamoxifen resistance was determined by depleting NgBR in these cell lines using previously validated small interfering RNA (siRNA). The effects of 4-OHT on cell viability and apoptosis were determined using well-accepted methods such as clonogenic survival assay and Annexin V/propidium iodide staining. The alteration of EGF-stimulated signaling and gene expression was determined by western blot analysis and real-time PCR, respectively. Results NgBR knockdown with siRNA attenuates EGF-induced phosphorylation of ERα and restores the sensitivity to tamoxifen in ERα-positive breast cancer cells. Mechanistically, our data demonstrated that NgBR knockdown increases the protein levels of p53 and decreases survivin, which is an apoptosis inhibitor. Conclusions These results suggested that NgBR is a potential therapeutic target for increasing the sensitivity of ERα-positive breast cancer to tamoxifen.

NgBR (NUS1) mRNA expression data were retrieved from a gene-expression profiling dataset (225071_x from Kaplan–Meier Plot database) of 755 patients with ERα-positive breast cancer and 335 patients with ERα-positive breast cancer treated with endocrine therapy. Kaplan–Meier analysis revealed significantly reduced relapse-free survival (RFS) (p

Raman spectroscopy has been widely used as an important clinical tool for real-time in vivo cancer diagnosis. Raman information can be obtained from whole organisms and tissues, at the cellular level and at the biomolecular level. The aim of this paper is to review the newest developments of Raman spectroscopy in the field of breast cancer diagnosis and treatment. Raman spectroscopy can distinguish malignant tissues from noncancerous/normal tissues and can assess tumor margins or sentinel lymph nodes during an operation. At the cellular level, Raman spectra can be used to monitor the intracellular processes occurring in blood circulation. At the biomolecular level, surface-enhanced Raman spectroscopy techniques may help detect the biomarker on the tumor surface as well as evaluate the efficacy of anticancer drugs. Furthermore, Raman images reveal an inhomogeneous distribution of different compounds, especially proteins, lipids, microcalcifications, and their metabolic products, in cancerous breast tissues. Information about these compounds may further our understanding of the mechanisms of breast cancer.