The real-world application of tracers for axillary sentinel lymph node biopsy (SLNB) for breast cancer (BC) after neoadjuvant chemotherapy (NAC) in China was unknown. We analyzed the use of individual tracers or combinations and number of SLNs in patients with BC who underwent SLNB with or without axillary lymph node dissection (ALND) after NAC in 20 hospitals in ten years. A total of 1251 BC patients underwent SLNB or SLNB + ALND after NAC, including 853 (68.2%, 853/1251) with a single tracer, predominantly Methylene blue (MB) (60.1%, 752/1251); and 398 (31.8%, 398/1251) with dual tracers, mainly MB combined with radioisotope (RI) (18.1%, 226/1251).The results showed that the predominance of the MB single-tracer method for SLNB after NAC limits the popularity of SLNB in patients with BC after NAC in China. MB combined with RI is the main dual-tracer method, and detects SLNs more effectively than MB alone.

This study aimed to evaluate the survival outcomes of neoadjuvant radiochemotherapy (NARCT) for early breast cancer. Female patients ≤ 80 years old with unilateral T1-T4 invasive ductal breast cancer treated with neoadjuvant chemotherapy (NAC) and radiation therapy (RT) between 2006 and 2015 were enrolled from SEER database. Baseline differences in clinical and pathological characteristics were evaluated using chi-square test. The survival outcomes were estimated by Kaplan–Meier analysis and compared using Cox hazards models. The effects of baseline differences on survival outcome in patients treated with neoadjuvant radiation therapy (NART) and post-operation radiation therapy (PORT) were circumvented by propensity score matching (PSM). Altogether 14,151 patients receiving NAC and RT were enrolled, among whom 386 underwent NART. Based on a 1:4 PSM cohort, NART was an independent unfavorable prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) for the whole cohort. However, among patients receiving breast conserving surgery (BCS) (HR 1.029, P = 0.915 for BCSS; HR 1.003, P = 0.990 for OS) or implant-based immediate breast reconstruction (IBR) (HR 1.039, P = 0.921 for BCSS; HR 1.153, P = 0.697 for OS), those treated with NART had similar survival outcomes compared with patients treated with PORT. In conclusion, NARCT was a safe and feasible approach for patients undergoing BCS and IBR.

PurposeThis study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram.MethodsThe CSBrS-012 study (2010–2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally.ResultsIn total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively.ConclusionWe present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

OBJECTIVE:To evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer. DESIGN:Randomised, multicentre, open label, phase 3 trial. SETTING:7 cancer centres in China between 3 January 2016 and 17 July 2023. PARTICIPANTS:Female patients aged 18-70 years with early triple negative breast cancer after definitive surgery. INTERVENTIONS:After risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168). MAIN OUTCOME MEASURES:The primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety. RESULTS:Among the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v 80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v 83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v 91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred. CONCLUSIONS:The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity. TRIAL REGISTRATION:ClinicalTrials.gov NCT02641847.

525 Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with variable clinical outcomes. We have previously classified patients with TNBC into high- and low-risk groups based on a multigene signature. In this study, we aimed to evaluate the feasibility of utilizing a multigene signature to tailor individualized adjuvant therapy for patients with operable TNBC. Methods: This multicenter, open-label, randomized, phase 3 trial was conducted at 7 cancer centers in China. We included female patients aged 18-70 years with early TNBC after definitive surgery (histologically confirmed axillary lymph node-positive or lymph node-negative with tumor diameter >10 mm). After categorization using the integrated signature, high-risk patients were randomized (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (TEC-GP; arm A), or the standard four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (EC-T; arm B). Low-risk patients received the same adjuvant chemotherapy as arm B (arm C). The primary endpoint was disease-free survival (DFS) in the intention-to-treat analysis of arm A versus arm B. Results: Between January 2016 and July 2023, 504 patients (336 high-risk and 168 low-risk; median age, 52 years; 488 with T1-2 tumors; 263 with node-positive disease) were recruited. At a median follow-up of 45.1 months, the 3-year DFS rates were 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.28 to 0.95; P = 0.030). Intensive chemotherapy improved DFS relative to standard therapy irrespective of tumor size and nodal status. The 3-year RFS was 92.6% in arm A and 83.2% in arm B (HR, 0.50; 95% CI, 0.25 to 0.98; P = 0.039). The groups did not differ in OS (HR, 0.58; 95% CI, 0.22 to 1.54; P = 0.267; 3-year OS, 98.2% vs 91.3%). Upon receiving the same chemotherapy regimen, patients in arm C had significantly higher DFS (HR, 0.57; 95% CI, 0.33-0.98; P = 0.038; 3-year DFS, 90.1% vs 80.6%), RFS (HR, 0.42; 95% CI, 0.22-0.81; P = 0.007; 3-year RFS, 94.5% vs 83.2%) and OS (HR, 0.14; 95% CI, 0.03-0.61; P = 0.002; 3-year OS, 100% vs 91.3%) compared to patients in arm B. The incidence of grade 3 to 4 treatment-related adverse. events for arms A, B and C, respectively, were thrombocytopenia (14.1%, 2.5%, 1.8%), febrile neutropenia (9.9%, 4.3%, 4.9%), anemia (5.8%, 1.9%, 1.8%), nausea (7.0%, 3.7%, 4.9%), vomiting (8.3%, 4.3%, 4.9%) and myalgia (2.6%, 5.6%, 5.5%). There were no treatment-related deaths. Conclusions: The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable TNBC. Intensive regimens incorporating GP into anthracycline/taxane-based therapy improves survival with manageable toxicity. Clinical trial information: NCT02641847 .

MicroRNAs (miRNAs) have attracted significant attention in the field of cancer research as a promising class of biomarkers. However, precise, sensitive, and specific detection of miRNAs still confronts challenges due to their dynamic expression, low abundance, and high sequence similarity among families. The highly sensitive silicon nanowires (SiNWs) biosensors are limited by little interface discrepancy within the SiNWs, which has the potential to affect the final output results. In this study, the calibration of the SiNWs biosensor was initially suggested to be conducted through photo response. This approach successfully mitigated the impact of preparation and modification procedures, resulting in an enhanced correlation between the biosensor and q-PCR for the identification of breast cancer miRNA. Specifically, the correlation coefficient was raised from below 0.5 to above 0.8. Furthermore, the uncharged peptide nucleic acid (PNA) was used for device modification in order to address the issue of detecting miRNAs with a total length in below 0.01×PBS buffer. It was shown that the PNA probe exhibited greater sensitivity compared to the DNA probe in 0.001×PBS buffer. Significantly, the improved biosensor exhibited favorable selectivity and was capable of identifying single base mismatch. The sensor exhibited a high level of sensitivity in detecting miRNA within a concentration range of 1 fM to 10 pM when applied to actual human blood samples. The biosensor exhibited an excellent level of reproducibility in the analysis of spiked samples, achieving a recovery rate of 91 %, without requiring RNA extraction or amplification procedures. The biosensor has the capability to directly detect miRNA in authentic clinical samples, hence demonstrating significant promise for the timely diagnosis of cancer via the use of miRNA as biomarkers.

AIM:This study aims to identify suitable candidates for axillary sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) among clinical N2 (cN2) triple-negative (TN) or HER2 positive (HER2+）breast cancer patients following neoadjuvant therapy（NAT）. BACKGROUND:Despite the substantial axillary burden in cN2 breast cancer patients, high pathological response rates can be achieved with NAT in TN or HER2+ subtypes, thus enabling potential downstaging of axillary surgery. METHODS:A retrospective analysis was conducted on data from the CSBrS-012 study, screening 709 patients with initial cN2, either HER2+ or TN subtype, from January 1, 2010 to December 31, 2020. The correlation between axillary pathologic complete response (pCR) (yPN0) and breast pCR was examined. RESULTS:Among the 177 cN2 patients who achieved breast pCR through NAT, 138 (78.0 %) also achieved axillary pCR. However, in the 532 initial clinical N2 patients who did not achieve breast pCR, residual axillary lymph node metastasis persisted in 77.4 % (412/532) of cases. The relative risk of residual axillary lymph node metastasis in patients who did not achieve breast pCR was 12.4 (8.1-19.1), compared to those who did achieve breast pCR, P < 0.001. CONCLUSION:For cN2 TN or HER2+ breast cancer patients who achieve breast pCR following NAT, consideration could be given to downstaging and performing an axillary SLNB or TAD.

Increased expression of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is associated with immune evasion in breast cancer (BC). The aim of this study to elucidate the role of LILRB2 in BC progression. LILRB2 expression in tumor tissues was detected by immunohistochemical staining. Human leukocyte antigen A (HLA-A) expression in BC cells was detected by Western blotting, and HLA-A ubiquitination was detected by immunoprecipitation and histidine pulldown assay. An in-situ tumor model was established in nude BALB/c mice to verify the role of LILRB2 in immune escape. Finally, the functions and potential mechanisms of LILRB2 in BC progression were explored using in silico data. LILRB2 was upregulated in BC tissues and cells, and correlated positively with poor prognosis. LILRB2 promoted BC progression by downregulating HLA-A expression. Mechanistically, LILRB2 facilitates the ubiquitination and subsequent degradation of HLA-A by promoting the interaction between the ubiquitin ligase membrane-associated ring finger protein 9 (MARCH9) and HLA-A. In syngeneic graft mouse models, LILRB2-expressing BC cells evaded CD8 + T cells and inhibited the secretion of cytokines by the cytotoxic CD8 + T cells. LILRB2 downregulates HLA-A to promote immune evasion in BC cells and is a promising new target for BC treatment.

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.

Purpose The prediction of axillary lymph node status after neoadjuvant chemotherapy (NAC) becoming critical because of the advocation of the de-escalation of axillary management. We investigate associated factors of axillary upstaging in clinical node-negative(cN0) breast cancer patients receiving NAC to develop and validate an accurate prediction nomogram; Methods We retrospectively analyzed 2101 breast cancer patients with stage of cT1-3N0 treated by NAC and subsequent surgery between 2010 and 2020 in twenty hospitals across China. Patients randomly divided into a training set and validation set (3:1). Univariate and multivariate logistic regression analysis were performed, after which a nomogram was constructed and validated; Results In total, pathologic node negativity (ypN0) achieved in 1552 (73.9%) patients and another 549(26.1%) patients upstaged to pathologic node positive (ypN+). Breast pathologic complete response (bpCR) was achieved in 499 (23.8%) patients and non-bpCR in 1602 (76.3%) patients. A nomogram was established by ER, tumor histology, NAC regimen, cycle of NAC treatment, and the bpCR, which were confirmed by multivariate logistic analysis as independent predictors of nodal upstaging in the training cohort (n = 1576). The area under the receiver operating characteristic curve (AUC) of the training cohort and validation cohort were 0.74 (95%CI, 0.64–0.71) and 0.76 (95% CI, 0.63–0.75) respectively; Conclusion We present a nomogram with a nationwide large sample data which can effectively predict axillary upstaging after neoadjuvant chemotherapy to give better advice for individualized axillary lymph node management of breast cancer.

年轻乳腺癌患者妊娠率远低于普通人群,与患者对肿瘤复发的担忧、化疗所致的卵巢功能减退、内分泌治疗周期漫长、缺乏专业化多学科协作团队保驾护航等因素相关.目前,有关年轻乳腺癌患者肿瘤治疗前实施生育力保存、治疗后成功妊娠并生产的数据有限.为顺利开展年轻女性乳腺癌患者生育力保存工作,促进患者身心健康和社会角色回归,提升其子代健康水平,本文就影响生育力的因素、生育力保存的合适人群和对乳腺癌预后的影响及乳腺癌生育力的保存时机、方式、恢复时机等作一述评.

Background: In the era of targeted therapy, whether patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are exempted from anthracycline usage in the neoadjuvant setting is controversial. Objectives: Our objective was to retrospectively analyze the differences in pathological complete remission (pCR) rates between the anthracycline group and the nonanthracycline group. Design: The CSBrS-012 study (2010-2020) included female primary breast cancer patients with neoadjuvant chemotherapy (NAC) who underwent standard breast and axillary surgery post-NAC. Methods: A logistic proportional hazard model was applied to estimate the association of covariates with pCR. Propensity score matching (PSM) was performed to balance the differences in baseline characteristics, and subgroup analyses were performed using the Cochran-Mantel-Haenszel test. Results: A total of 2507 patients were enrolled: the anthracycline group (n = 1581, 63%) and the nonanthracycline group (n = 926, 37%). A pCR was recorded in 17.1% (271/1581) of patients in the anthracycline group and in 29.3% (271/926) in the nonanthracycline group, and the difference in the pCR rate between the two groups was statistically significant [odds ratio (OR) = 2.00, 95% confidence interval (CI) (1.65-2.43); p < 0.001). In the subsequent subgroup analysis, substantial differences in pCR rates between the anthracycline and nonanthracycline groups were detected in the nontargeted [OR = 1.91, 95% CI (1.13-3.23); p = 0.015] and dual-HER2-targeted populations [OR = 0.55, 95% CI (0.33-0.92); p = 0.021) before PSM, whereas differences vanished after PSM. The pCR rates between the anthracycline and nonanthracycline groups did not differ for the single target population, either before or after PSM. Conclusion: In the presence of trastuzumab and/or pertuzumab, the pCR rate of patients with HER2-positive breast cancer receiving anthracycline was not superior to that of patients receiving nonanthracycline. Thus, our study further provides clinical evidence for exempting anthracycline treatment in HER2-positive breast cancer in the era of targeted therapy.

Background. There is limited knowledge about the role of cancer-associated fibroblasts (CAF) in the tumor microenvironment of triple-negative breast cancer (TNBC). Methods. Three hundred and thirty-five TNBC samples from four datasets were retrieved and analyzed. In order to determine the CAF subtype by combining gene expression profiles, an unsupervised clustering analysis was adopted. The prognosis, enriched pathways, immune cells, immune scores, and tumor purity were compared between CAF subtypes. The genes with the highest importance were selected by bioinformatics analysis. The machine learning model was built to predict the TNBC CAF subtype by these selected genes. Results. TNBC samples were classified into two CAF subtypes (CAF+ and CAF-). The CAF- subtype of TNBC was linked to the longer overall survival and more immune cells than the CAF+ subtype. CAF- and CAF+ were enriched in immune-related pathways and extracellular matrix pathways, respectively. Bioinformatics analysis identified 9 CAF subtype-related markers (ADAMTS12, AEBP1, COL10A1, COL11A1, CXCL11, CXCR6, EDNRA, EPPK1, and WNT7B). We constructed a robust random forest model using these 9 genes, and the area under the curve (AUC) value of the model was 0.921. Conclusion. The current study identified CAF subtypes based on gene expression profiles and found that CAF subtypes have significantly different overall survival, immune cells, and immunotherapy response rates.

BackgroundAchieving pathologic complete response (pCR) because of neoadjuvant therapy has been correlated with long-term clinical benefit, however, luminal-like tumors achieve a lower rate of pCR in comparison with other subtypes. The Shanghai Pudong (SHPD) 002 trial compares neoadjuvant chemotherapy concurrently with or with different estrogen deprivation therapy separately in premenopausal and postmenopausal patients with locally advanced breast cancer. MethodsIn this prospective, multicentre, neoadjuvant, phase III trial, 236 patients with locally advanced breast cancer were randomly assigned (2:1) to receive neoadjuvant chemotherapy (NCT) with gonadotropin-releasing hormone agonist (GnRHa) in premenopausal women or letrozole in postmenopausal women compared with chemotherapy alone. The primary endpoint was pCR (ypT0/is/ypN0). Secondary endpoints included disease-free survival, overall survival, and safety. This trial is registered with ClinicalTrials.gov, number NCT NCT02221999.Results A total of 236 patients were included. pCR was achieved by 20.4% in the chemotherapy plus ET group and 38.6% in the chemotherapy group. In postmenopausal patients, pCR was observed in 22.6% when treated with letrozole, 32.4% with NCT alone (p=0.276). Premenopausal patients with NCT and GnRHa achieved a significantly lower pCR of 18.8% than those of 42.9% in patients with NCT alone(p=0.003). A posthoc analysis showed CPS+EG score 0-3 was significantly more probable in patients with GnRHa (OR, 0.245; 95% CI, 0.072 to 0.832, P=0.024) than in those without GnRHa in the premenopausal patients who didn’t achieve near-pCR. After a median follow-up of 45 months, there was no significant difference concerning disease-free survival (DFS) (p=0.874) or overall survival (OS) (P =0.947) between the 2 postmenopausal groups. GnRHas significantly improved survival outcome in premenopausal patients (3-year OS, 100% with GnRHas, vs 88.2% without; log-rank p=0.034). Improved DFS (log-rank p = 0.001) and OS (log-rank p=0.003) were strongly associated with pCPS+EG score and GnRHa usage in premenopausal patients.ConclusionsConcurrent administration of GnRHas during neoadjuvant chemotherapy improves OS in premenopausal patients, though it does not increase the pCR rate. The adoption of the CPS+EG score may be a better surrogate endpoint for survival outcomes. The addition of letrozole to neoadjuvant chemotherapy confers no therapeutic advantage in terms of tumor response or survival outcome. Citation Format: Liheng Zhou, Shuguang Xu, Xiaohong Xue, Yinzhou Zhang, Bei Gu, Baoxing Lin, Junwen Bai, Hongwei Zhang, Kejin Wu, Yanping Lin, Yumei Ye, Yueyao Du, Xiaonan Sheng, Yaqian Xu, Jie Zhang, Wenjin Yin, Jinsong Lu. Efficacy, safety and survival of neoadjuvant chemotherapy with different estrogen deprivation stratified by menstrual status versus chemotherapy alone in locally advanced breast cancer (SHPD002)—— A randomized multicentre, open-label, phase 3 Triab [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-02.

BackgroundHere, we describe an innovative oncoplastic technique for small to medium volume breasts with a tumor in the lower quadrant and this technique could provide sufficient tissue to avoid visible defects after tumor removal and help reshape the natural shape of the breast.MethodsA detailed procedure for the folding flap technique is described step by step. Then, the results of a retrospective analysis of patients treated using this technique, including complications and disease recurrence rate, between January 2017 and November 2021 are reported. Aesthetic outcomes were evaluated on a 5-point scale proposed by the Paris Breast Center.ResultsA total of 52 patients underwent surgery with the folding flap technique, The average operation time was 98.4 min (range, 75–120 min), and the mean bleeding volume was 56.5 mL (range, 20–100 mL). A margin-positive result was confirmed in 1 patient who underwent re-excision. Short-term postoperative complications were observed in 7 patients, including 4 with fat liquefaction, 2 with seroma, and 1 with skin redness and swelling. No flap necrosis was observed. The median follow-up time was 28.6 months (range, 9–58 months), and 2 patients experienced local recurrence. The mean aesthetic score was 4.7 points, with 36 patients scoring 5 points and 26 patients scoring 4 points, respectively.ConclusionsThe folding flap technique, as an innovative and favorable oncoplastic technique for treating small- to medium-volume breasts with a tumor in the lower quadrant, could retain sufficient tissue to fill the residual cavity after the operation while improving the aesthetic outcome of the breast.

自国家卫生健康委号召全面开展预约诊疗管理以来,各大医院的预约诊疗管理日趋成熟,预约就诊占比明显提升.与此同时,门诊优质号源被线上抢占、倒卖的现象也日益凸显,成为现阶段加重老百姓"看病难"现象的主要原因之一.在已普遍实行预约实名制和额度限制等基本管控手段基础上,通过对数据、行为的积累、监测和持续的科学分析与回溯,形成从规则、系统、流程、成本投入等方面对门诊线上预约的管理"组合拳",最大程度切断恶意刷号、贩号等不实号源的占用、错配及浪费问题,为广大群众创造优质的门诊预约诊疗环境.

Background This study aimed to construct a tumor microenvironment (TME)-related risk model to predict the overall survival (OS) of patients with breast cancer. Methods Gene expression data from The Cancer Genome Atlas was used as the training set. Differentially expressed gene analysis, prognosis analysis, weighted gene co-expression network analysis, Least Absolute Shrinkage and Selection Operator regression analysis, and Wald stepwise Cox regression were performed to screen for the TME-related risk model. Three Gene Expression Omnibus databases were used to validate the predictive efficiency of the prognostic model. The TME-risk-related biological function was investigated using the gene set enrichment analysis (GSEA) method. Tumor immune and mutation signatures were analyzed between low- and high-TME-risk groups. The patients’ response to chemotherapy and immunotherapy were evaluated by the tumor immune dysfunction and exclusion (TIDE) score and immunophenscore (IPS). Results Five TME-related genes were screened for constructing a prognostic signature. Higher TME risk scores were significantly associated with worse clinical outcomes in the training set and the validation set. Correlation and stratification analyses also confirmed the predictive efficiency of the TME risk model in different subtypes and stages of breast cancer. Furthermore, immune checkpoint expression and immune cell infiltration were found to be upregulated in the low-TME-risk group. Biological processes related to immune response functions were proved to be enriched in the low-TME-risk group through GSEA analysis. Tumor mutation analysis and TIDE and IPS analyses showed that the high-TME-risk group had more tumor mutation burden and responded better to immunotherapy. Conclusion The novel and robust TME-related risk model had a strong implication for breast cancer patients in OS, immune response, and therapeutic efficiency.

Background Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods. Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan-Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. Results 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Conclusion Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC.

目的:探讨年轻早期乳腺癌患者在面对生育力保存决策时的真实体验.方法:采用质性研究中的现象学研究方法,对15例年轻女性早期乳腺癌患者进行半结构式深入访谈,根据Colaizzi?7步分析法对原始资料进行整理分析.结果:提炼出4个主题,即担心、对生育的关注动态变化且因人而异、面临决策困境、决策支持的需求.结论:年轻乳腺癌患者在生育力保存决策上面临较大的决策困境,应加强全体医护人员对年轻乳腺癌患者生育力保存的认识,开发适宜的辅助生育决策资源,培养生育力保存的专业人员,提供及时的、全面的、个体化的生育信息支持,开展完善的生育管理计划.