HER2-Low Status Was Associated With Better Breast Cancer-Specific Survival in Early-Stage Triple-Negative Breast Cancer.

BACKGROUND: Based on the association between the hormone receptor and the status of human epidermal growth factor receptor 2 (HER2)-low, we investigated the clinicopathological and prognostic characteristics of the HER2-low status in early-stage triple-negative breast cancer (TNBC). METHODS: We collected the data of patients with TNBC who received treatment at our hospital and compared the pathological complete response (pCR) rate, overall survival (OS), and breast cancer-specific survival (BCSS) between the HER2-0 and HER2-low subtypes. RESULTS: A total of 1445 patients were included in the study, of which 698 patients (48.3%) showed HER2-low status. A similar pCR rate was observed between HER2-0 and HER2-low patients (34.9% vs. 37.4%; P = .549). T staging, N staging, and HER2 status were associated with BCSS, whereas T staging and N staging were associated with OS. Patients with the HER2-low status showed better BCSS than those with the HER2-0 status (96.6% vs. 93.7%; log-rank P = .027). In patients with non-pCR, the BCSS of the HER2-low subgroup was better than that of the HER2-0 subgroup (log-rank P = .047); however, no similar result was observed in patients with pCR. In patients with stage III, the BCSS and OS of the HER2-low subgroup were better than those of the HER2-0 subgroup (BCSS, log-rank P = .010; OS, log-rank P = .047). No similar results were observed in patients with stages I and II. CONCLUSION: The HER2-low expression was associated with better BCSS in TNBC, especially in the high-risk groups, suggesting that HER2-low breast cancer is a potential independent biological subtype.

Micro-computed tomographic evaluation of the shaping ability of three nickel-titanium rotary systems in the middle mesial canal of mandibular first molars: an ex vivo study based on 3D printed tooth replicas.

BACKGROUND: The preparation of the middle mesial (MM) canal of mandibular molars represents a challenge because it is often curved, narrow, and close to the root concave. The purpose of this study was to evaluate the ex vivo shaping ability of 3 nickel-titanium (NiTi) rotary systems in the MM canal using 3D printed resin tooth replicas. METHODS: A permanent mandibular first molar with a MM canal was acquired from a pool of extracted teeth and reproduced by a 3D printer. The resin tooth replicas (n = 18) were equally assigned to 3 groups for the evaluation of the shaping abilities of 3 NiTi rotary systems (OneShape [OS], Twisted Files [TF], and ProTaper Gold [PTG]) according to the manufacturer's recommendations. The tooth replicas were scanned by micro-computed tomography (micro-CT) twice before and after instrumentation of the mesiobuccal (MB), mesiolingual (ML), and MM root canals. After 3D reconstruction, the canal straightening, change of root canal volume and surface area, the mesial and distal canal wall thickness and canal transportation at the levels of 1, 2, and 3 mm below furcation were assessed. One-way variance analysis and Turkey's post hoc test were used for comparisons of the means among different groups, and paired-t test was used to compare the mesial and distal sides of the mesial roots. RESULTS: As compared with OS and TF, the use of PTG in preparation of MM canals resulted in significantly more straightening of canal curvature (p < 0.05), greater post-instrumentation canal volume and surface area, and thinner mesial and distal remaining canal wall thickness at 1, 2 and 3 mm below furcation (all p < 0.05). Regarding the root canal transportation in the mesiodistal direction, there was no significant difference among the 3 instruments (all p > 0.05) after the preparation of the MB and ML canals. However, in the MM canal, more pronounced transportation was detected in the PTG group at 2 mm below furcation, and in the TF group at 3 mm below furcation as compared with the other 2 systems (both p < 0.05). CONCLUSIONS: 3D printed tooth replicas have the advantages of consistency and can be an ideal model to evaluate the shaping ability of different instruments in the MM canal. OS and TF files performed similarly and both are appropriate for shaping the MM canal, while PTG may cause excessive and uneven resin removal, especially near the furcation, and may lead to root fragility and procedural errors.

Dyslipidemia is associated with a poor prognosis of breast cancer in patients receiving neoadjuvant chemotherapy.

BACKGROUND: Lipid metabolism disorders may be involved in the occurrence and development of breast cancer. This study aimed to investigate the serum lipid changes during neoadjuvant chemotherapy for breast cancer and the effect of dyslipidemia on the prognosis of breast cancer patients. METHODS: We collected the data from 312 breast cancer patients who underwent surgery after receiving standard neoadjuvant therapy. χ2 test and T-test were employed to analyze the effect of chemotherapy on the serum lipid metabolism of patients. The effects of dyslipidemia on the disease-free survival (DFS) of patients with breast cancer were analyzed by χ2 test and COX regression analysis. RESULTS: A total of 56 out of 312 patients (17.9%) suffered from relapse. The baseline serum lipid level of the patients was significantly correlated with their age and body mass index (BMI) (p < 0.05). Chemotherapy increased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol, but decreased the level of high-density lipoprotein cholesterol (p < 0.001). Preoperative dyslipidemia was significantly associated with the axillary pCR rate (p < 0.05). COX regression analysis revealed that the full-course serum lipid level (HR = 1.896 [95%CI 1.069-3.360]; p = 0.029), N stage (HR = 4.416 [95%CI 2.348-8.308]; p < 0.001) and the total pCR rate (HR = 4.319 [95%CI 1.029-18.135]; p = 0.046) acted as prognostic factors affecting DFS in breast cancer. The relapse rate in patients with a high level of total cholesterol was higher than that in patients with a high level of triglycerides (61.9% vs 30.0%; p < 0.05). CONCLUSIONS: Dyslipidemia deteriorated after chemotherapy. The full-course serum lipid level may thus serve as a blood marker for predicting breast cancer prognosis. Serum lipids should therefore be closely monitored in breast cancer patients throughout the treatment course, and patients with dyslipidemia should be treated in a timely manner.

A Nomogram for Identifying HR+/Her2- Breast Cancer Patients with Positive Sentinel Lymph Nodes and Omitted Axillary Lymph Node Dissection Who Need Abemaciclib Therapy.

BACKGROUND The efficacy of abemaciclib in high-risk patients with early-stage HR+/Her2- breast cancer has been verified by MonarchE. However, accurately determining the number of axillary lymph node (ALN) metastases remains challenging. The Z0011 trial changed the axillary management strategy, eliminating the need for axillary lymph node dissection (ALND) in patients with 1-2 sentinel lymph node (SLN) metastases. Therefore, further exploration is needed to identify patients who could benefit from abemaciclib therapy. MATERIAL AND METHODS This retrospective study included cT1-2N0M0 HR+/Her2- patients with 1-2 positive SLNs who underwent ALND. Clinicopathological data were collected, and logistic regression analyses identified independent predictors for ≥4 positive ALNs. A predictive nomogram was developed, and discrimination and calibration were evaluated using the C-index and calibration curve. Clinical efficacy was assessed using decision curve analysis (DCA). RESULTS We enrolled 444 patients, with 77 (17.3%) having ≥4 positive ALNs. Independent predictors for ≥4 positive ALNs included abnormal ALN on ultrasound, mammographic calcifications, T stage, and the number of positive SLNs. The nomogram demonstrated an AUC of 0.777 (95% CI: 0.735-0.815, P<0.001), and internal validation showed good calibration and discrimination (C-index, 0.802; 95% CI: 0.779-0.824). DCA revealed a positive net benefit for risk levels ranging from 5% to 54%. CONCLUSIONS This nomogram is a convenient and reliable tool to predict the risk of ≥4 positive ALNs in HR+/Her2- patients. It aids in protocol selection by identifying SLN-positive patients who may benefit from abemaciclib therapy without ALND.

Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial.

BACKGROUND: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. METHODS: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0-2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051. FINDINGS: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7-19·0). The intracranial objective response rate was 74·6% (95% CI 61·6-85·0; 44 of 59 patients) in cohort A and 42·1% (20·3-66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial. FUNDING: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Impact of Ipsilateral Supraclavicular Lymph Node Dissection (ISLND) for Breast Cancer Patients and a Nomogram for Predicting Ipsilateral Supraclavicular Pathological Complete Response (ispCR).

BACKGROUND: The purpose of this study was to evaluate the impact of ipsilateral supraclavicular lymph node dissection (ISLND) on the outcomes of breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM), and to evaluate the prognostic value of ipsilateral supraclavicular pathological complete response (ispCR). Meanwhile, a nomogram was constructed to predict ispCR. METHODS: We retrospectively reviewed the medical documents of 353 patients with ISLNM but no distant metastasis at presentation. Based on whether ISLND was performed, patients were divided into radiotherapy (RT) and ISLND + RT groups. The impact of ISLND was evaluated after propensity score matching, and the prognostic value of ispCR was also analyzed. A nomogram to predict the probability of ispCR was constructed based on clinicopathologic variables. RESULTS: After propensity score matching, we found that the use of ISLND was associated with a higher rate of ipsilateral supraclavicular relapse-free survival (ISRFS; p < 0.0001). Among 307 patients who underwent ISLND, ispCR was associated with a higher rate of ISRFS and disease-free survival (p = 0.018 and p = 0.00033, respectively). Furthermore, the nomogram constructed with number of axillary lymph node metastases, breast pCR, size of the ipsilateral supraclavicular lymph nodes after neoadjuvant chemotherapy (NAC), number of NAC cycles, and Ki67 level showed a good fit for predicting ispCR. CONCLUSION: For breast cancer patients with ISLNM but no distant metastasis, ISLND may be beneficial in some certain subtypes, and ispCR indicated a better prognosis. Our nomogram is well-fitted to predict the probability of achieving ispCR.

Knockdown of LINC00665 inhibits proliferation and invasion of breast cancer via competitive binding of miR-3619-5p and inhibition of catenin beta 1.

BACKGROUND: Long intergenic non-protein coding RNA00665 (LINC00665) plays a crucial tumorigenic role in many cancers, such as gastric cancer and lung adenocarcinoma. However, its role and mechanism of action in the progression of breast cancer (BC) are unknown. METHODS: LINC00665 expression levels were determined using quantitative polymerase chain reaction analysis with BC tissues and cell lines. BC cell proliferation was tested by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, whereas BC cell migration and invasion capabilities were analyzed by performing transwell migration assays. Percentages of apoptotic cells were measured by flow cytometry. Interactions between LINC00665 and miR-3169-5p were examined by performing luciferase reporter assays, and the expression levels of proteins, such as ß-catenin, were examined by western blot analysis. RESULTS: LINC00665 was expressed at high levels in BC tissues and cells. Upregulated LINC00665 expression correlated with tumor size and tumor, node, and metastasis stages, but not with the age of patients. LINC00665 knockdown inhibited BC cell proliferation, migration, and invasion, whereas it promoted apoptosis. Moreover, bioinformatics analysis and the luciferase reporter assay revealed that LINC00665 bound the microRNA (miR) miR-3619-5p. miR-3619-5p expression correlated negatively with LINC00665 expression in BC tissues. miR-3619-5p overexpression inhibited BC cell proliferation, migration, and invasion, but promoted apoptosis. Simultaneous knockdown of LINC00665 and miR-3619-5p led to increased cell proliferation, migration, and invasion, and inhibited apoptosis. Additionally, catenin beta 1, which encodes the ß-catenin protein, was the target gene of miR-3619-5p. ß-catenin expression clearly decreased after LINC00665 knockdown and miR-3619-5p overexpression, but increased after simultaneous knockdown of LINC00665 and miR-3619-5p. CONCLUSION: LINC00665 knockdown inhibited BC cell proliferation and invasion by binding miR-3619-5p and inhibiting ß-catenin expression.

Targeted axillary dissection after neoadjuvant chemotherapy for highly selective patients with initial cN1 breast cancer: A single-center prospective trial.

BACKGROUND: Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging). METHODS: This prospective trial included patients with initial pre-NAC cT1-3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated. RESULTS: A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30). CONCLUSIONS: In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%. REGISTRATION: chictr.org.cn , ChiCTR2100049093.

Impact of residual disease biomarkers on the prognosis of HER2-positive breast cancer following neoadjuvant therapy.

BACKGROUND: The changes in prognostic factors and clinicopathological characteristics of residual disease following neoadjuvant therapy (NAT) for breast cancer are important references for postoperative adjuvant therapy. The analyses of the relationship between the clinicopathological characteristics of residual diseases and the prognosis were not comprehensive in most previous studies. This study aimed to determine how prognostic factors changed following NAT and the impact of clinicopathological characteristics of residual disease on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: The study comprised 350 consecutive patients with HER2-positive breast cancer who had residual disease after surgery following NAT. The independent risk factors affecting the prognosis of HER2-positive breast cancer were analyzed using univariate and multivariate Cox regression analyses. Chi-square test and binary logistic regression were used to analyze the influencing factors of HER2 loss following NAT. RESULTS: The expression of prognostic factors changed significantly following NAT. A total of 44 patients (12.6%) had HER2 loss. HER2 status (immunohistochemistry (IHC) 3+ vs. IHC 2+/FISH+, p < 0.001) at baseline was associated with HER2 loss. In this investigation, the HER2 loss did not affect the prognosis. In univariate analysis, the decrease in Ki-67 (p < 0.001) after NAT was associated with improved prognosis, but this influence was lost in the Cox proportional hazards model. The ypN stage (p < 0.001), postoperative ER status (p = 0.020), Miller-Payne grade (p = 0.007), and targeted therapy (p = 0.003) were all independent prognostic factors. CONCLUSIONS: ER, PR, HER2, and Ki-67 changed significantly after NAT, but no impact of these changes on DFS was observed in this study. Postoperative N stage, postoperative ER status, MP grade, and targeted therapy were independent prognostic factors in patients with HER2-positive breast cancer after NAT.

Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy.

PURPOSE: Patients with human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. RESULTS: Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)-positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). CONCLUSION: Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: a single-arm phase II trial.

Immunotherapy combined with chemotherapy has been demonstrated to be effective in early triple-negative breast cancer (TNBC). In this single-arm, phase II study with Simon's two-stage design, we investigated the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC (NCT04213898). Eligible female patients aged 18 years or older with histologically confirmed treatment-naïve early TNBC were treated with camrelizumab (200 mg, on day 1), nab-paclitaxel (125 mg/m2, on days 1, 8, and 15), and epirubicin (75 mg/m2, on day 1) every three weeks for six cycles. The primary end point was the pathological complete response; secondary endpoints included safety, objective response rate, and long-term survival outcomes of event-free survival, disease-free survival, and distant disease-free survival. A total of 39 patients were enrolled between January 2020 and October 2021. Twenty-five patients achieved a pathological complete response (64.1%, 95%CI: 47.2, 78.8). The objective response rate was 89.7% (95%CI: 74.8, 96.7), including 35 patients with partial responses. Treatment-related adverse events of grade 3 or 4 occurred in 30 (76.9%) patients. In conclusion, the trial meets the prespecified endpoints showing promising efficacy and manageable safety of neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin chemotherapy in female patients with early TNBC. Long-term survival outcomes are still pending.

Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial.

CDK4/6 inhibitors have shown a synergistic effect with anti-HER2 therapy in hormone receptor (HR)-positive and HER2-positive breast cancer (BC). In this phase 2 study (NCT04293276), we aim to evaluate a dual-oral regimen of CDK4/6 inhibitor dalpiciclib combined with HER2 tyrosine kinase inhibitor pyrotinib as front-line treatment in women with HER2-positive advanced BC (n = 41) including those with HR-negative disease. The primary endpoint is the objective response rate, and secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. With a median follow-up of 25.9 months, 70% (28/40) of assessable patients have a confirmed objective response, meeting the primary endpoint. The median PFS is 11.0 months (95% CI = 7.3-19.3), and OS data are not mature. The most common grade 3 or 4 treatment-related adverse events (AEs) are decreased white blood cell count (68.3%), decreased neutrophil count (65.9%), and diarrhea (22.0%). Most AEs are manageable, and no treatment-related deaths occur. These findings suggest that this combination may have promising activity and manageable toxicity. Further investigation is needed.

Novel printed electrode immunosensors for Schistosoma japonicum.

OBJECTIVE: To improve the sensitivity and the linear range of electrochemical immunosensor to detect Schistosoma japonicum (S. japonicum) antibody. METHODS: Carbon inks and silver/silver chloride inks were printed on a polyethylene terephthalate (PET) board to make a two-electrode test strip, where carbon was the working electrode and S. japonicum soluble egg antigen (SEA) was fixed at one end of working electrode by different methods; silver/ silver chloride electrode was used as control. We tested the valency of the antibody by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in an electrochemistry workstation, and conducted comparison with the results of ELISA. Two new immunosensing electrodes have been developed, based on glutaraldehyde cross-linked (GA) or chitosan-glutaraldehyde cross-linked (Chit-GA) transducer fixing S. japonicum antigen. We tested the titer of the antibody by means of CV and DPV. RESULTS: Our experimental S. japonicum antigen (50 µg/L) is the optimal test concentration for the GA sensor, and 10 µg/L for Chit-GA sensors. The immune reaction time of both electrodes is all essentially complete in 1 minute. The linear range for S. japonicum antibody in human positive serum sample detection by the glutaraldehyde cross-linked immunosensor is 1:1000 to 1:400, and by the chitosan-glutaraldehyde cross-linked immunosensor is 1:1000 to 1:500. As the concentration of dilution ratio of S. japonicum antibody in human positive serum sample increased, the test value of DPV increased proportionally. CONCLUSION: GA sensor and Chit-GA cross-linked S. japonicum sensors have high sensitivity and broad linear range response, and both exhibited a good linear relationship between the DPV signal and the test antibody titer.

Exploration of prognostic factors and the value of adjuvant chemotherapy in T1a,bN0M0 triple-negative breast cancer: a prospective cohort study based on the SEER database.

Background: There are limited published studies on the prognostic predictors and the value of adjuvant chemotherapy (CT) in T1a,bN0M0 triple-negative breast cancer (TNBC) after local therapy. Therefore, the aim of the present study was to explore the prognostic predictors and the value of adjuvant CT in this population. Methods: We identified T1a,bN0M0 TNBC cases registered in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. We analyzed associations between patient characteristics and overall survival (OS) and breast cancer-specific mortality (BCSM), and differences in OS and BCSM in a CT and no chemotherapy (no CT) cohort before and after propensity score matching. Results: Of the 3,065 SEER patients, 1,534 (50.0%) received adjuvant CT. The median follow up was 57 months (interquartile range: 39-75 months). The 5-year OS and cumulative BCSM were 93.6% and 3.3%, respectively. Younger age was not associated with lower OS or higher BCSM in the total and no CT cohorts. Higher histologic grade was associated with lower OS in the no CT cohort, and T1b tumors were associated with higher BCSM in the total cohort. Multivariable analysis showed no association between adjuvant CT and OS or BCSM. Conclusions: Patients with T1a,bN0M0 TNBC had an excellent prognosis with or without adjuvant CT. For this population, higher histologic grade and larger tumor size were predictors of poor prognosis, although the effect of age was complex. Our data did not support using adjuvant CT in patients with T1a,bN0M0 TNBC.

Optimal Frequency for Changing Single-Use Enteral Delivery Sets in Infants after Congenital Heart Surgery: A Randomized Controlled Trial.

Objective We aimed to assess the optimal frequency for changing single-use enteral delivery sets during postoperative enteral feeding in infants with congenital heart disease (CHD).Methods We enrolled 120 CHD infants who were fed using an enteral nutrition pump directly connected to a milk bottle with a single-use enteral delivery set in a four-arm randomized controlled trial (ChiCTR2000039544). Patients were randomized into four groups based on the replacement frequency of the enteral delivery set (6 h, 12 h, 18 h, and 24 h groups). The primary outcome was the percentage of contaminated enteral delivery sets (overgrowth of microbiota and colonization of pathogenic bacteria). Secondary outcomes included evidence of infection, gastrointestinal tolerance, intestinal microflora dysbiosis, and healthcare costs.Results The percentages of microbial overgrowth detected in the 6 h, 12 h, 18 h, and 24 h groups were 6.7%, 30.0%, 46.7%, and 80%, respectively (P < 0.001). Significant differences were observed between the 6 h and 18 h groups (P < 0.001), the 6 h and 24 h groups (P < 0.001), and the 18 h and 24 h groups (P = 0.007). Meanwhile, pathogenic bacterial colonization was detected in 0, 4, 6, and 11 delivery sets in the 6 h, 12 h, 18 h, and 24 h groups, respectively (P = 0.002). No difference in clinical symptoms was found among the four groups. The total cost per patient in the 12 h group and the 18 h group was 340.2 RMB and 226.8 RMB, respectively.Conclusion Taking into consideration both microbial overgrowth and cost-effectiveness, the results of this study indicate that for children receiving continuous enteral feeding following CHD surgery, the optimal frequency for changing the single-use enteral delivery set when formula reconstituted from powder is used is 18 hours.

Effect of the HER-2/CEP17 ratio in IHC 2+/FISH-amplified breast cancer on pathological complete response to neoadjuvant pertuzumab and trastuzumab treatment-a retrospective cohort study.

Background: Human epidermal growth factor receptor-2 (HER-2) protein expression level could serve as a predictor of pathological complete response (pCR) to neoadjuvant trastuzumab-containing regimens. The aim of the present study was to evaluate whether pCR to neoadjuvant trastuzumab and pertuzumab treatment is dependent on the level of the HER-2/CEP17 (chromosome enumeration probe 17) ratio in immunohistochemistry (IHC) 2+/fluorescence in situ hybridization (FISH)-amplified breast cancer. Methods: Patients with primary IHC 2+/FISH-amplified breast cancer who underwent neoadjuvant anti-HER-2 dual-targeted therapies were retrospectively included between January 1, 2020 and May 30, 2021. The primary predictive variable was HER-2/CEP17 ratio, and the primary outcome variable was pCR. Other variables consisted of age, menopausal status, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PgR), and Ki-67. Association between clinicopathologic variables and pCR was evaluated using the chi-square test and logistic regression analysis. Results: The median age of the patients was 51.78 years (25-67 years), and 50.7% of the patients were in the premenopausal stage. The clinical stage at diagnosis was Stage III in 38 patients (55.1%). Of all patients, 40.6% patients were estrogen receptor positive, and 75.4% patients had a Ki-67 index of ≥30%. The overall pCR (ypN0/isypN0) rate was 31.9%. Patients with HER-2/CEP17 ratio ≥6.0 had a pCR rate of 55.0%, it was statistically higher than 22.4% in patients with HER-2/CEP17 ratio <6.0. Logistic regression analysis confirmed the independent association between HER-2/CEP17 ratio and pCR (P=0.020, OR: 5.203, 95% CI: 1.302-20.783). Conclusions: A HER-2/CEP17 ratio ≥6.0 might be related to more achievement of pCR in the neoadjuvant anti-HER-2 dual-targeted therapies. Further studies are needed to validate the finding.

Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen.

(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181−0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554−1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.

Pathological response and predictive role of tumour-infiltrating lymphocytes in HER2-positive early breast cancer treated with neoadjuvant pyrotinib plus trastuzumab and chemotherapy (Panphila): a multicentre phase 2 trial.

PURPOSE: Panphila evaluated pyrotinib plus trastuzumab, docetaxel and carboplatin as neoadjuvant therapy for early breast cancer (BC), and investigated the predictive role of immune cell subpopulations. PATIENTS AND METHODS: In this multicentre phase 2 study, patients with human epidermal growth factor receptor 2-positive, stage T2-3N0-3M0 BC received pyrotinib 400 mg once daily plus docetaxel (75 mg/m2, day 1), carboplatin (6 mg/mL/min, day 1) and trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance dose, day 1) for 6 cycles of 21 days each. Simon's 2-stage design was adopted. The primary end-point was pathological complete response (pCR, ypT0/is ypN0) rate. Tumour-infiltrating lymphocytes (TILs) were assessed by haematoxylin and eosin staining and multiplex immunohistochemistry. RESULTS: In the modified intention-to-treat population (n = 69), 38 patients (55.1%) achieved pCR. In the safety population (n = 74), the most common grade ≥3 adverse events were diarrhoea (43.2%), anaemia (37.8%), vomiting (16.2%) and platelet count decrease (10.8%). No treatment-related deaths occurred. Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by stromal (s)-CD20+, s-CD8+ and s-CD4+ TILs. Unsupervised hierarchical clustering of stromal immune markers identified a group of patients characterised by high s-CD20+, s-CD8+, s-CD4+ and s-FOXP3+ immune cells infiltration, which was independently associated with pCR. CONCLUSION: Neoadjuvant pyrotinib plus trastuzumab-based chemotherapy exhibits promising efficacy and manageable toxicity in patients with human epidermal growth factor receptor 2-positive early BC, and thus phase 3 trials are warranted. Our findings also contribute to understanding the potential role of the immune microenvironment in response to neoadjuvant pyrotinib-based therapy.

Artificial preparation, indoor passage, and nature breed of Oncomelania hupensis infected with Schistosoma Japonicum.

OBJECTIVE: To prepare the infected Oncomelania hupensis by artificial method for the research on the activity, vaccine, and genetic variation of Schistosoma Japonicum (S. Japonicum). METHODS: The mature eggs of S. Japonicum were collected by Nylon silk method and the miracidia were incubated under appropriate conditions. Negative snails were infected with miracidia in different proportion by means of individual or collective infection to seek the best method and proportion of infection between miracidia and snails. Infected snails were divided into 12 groups in total. I-VI groups were for individual infection and VII-XII groups were for collective infection. There were 200 snails in each group. The infection ratios between snails and miracidia in Group I-VI or VII-XII were 1:0,1:5,1:10,1:15,1:20,1:25, respectively. The infected snails were screened, numbered, and reared singly. The amount of cercariae was calculated once every 10 days until the infected snails died. Then cercariae shedding quantity, infection quantity, and mortality of infected snails in every group were compared to find the best infection method and the best infection proportion between miracidia and snails. The cercariae were collected from the first generation of infected snails and were used to infect experimental animals. The mature eggs of S. Japonicum were saved from the infected experimental animals and incubated to get miracidia. The snails were artificially infected by miracidium to get the second generation of infected snails. The developmental rates of adult worms, the egg density in fecal and liver were compared between artificially and naturally infected snails. Results In individual infection Group I-VI,the average infection value of snails were 0 ± 0,22.7 ± 4.2,31.7 ± 4.5,53.0 ± 5.3,39.3 ± 5.9,32.7 ± 4.7,the average fatality of snails were 21.7 ± 3.1,25.0 ± 3.6,31.3 ± 4.9,44.7 ± 6.5,78.3 ± 9.5,89.7 ± 13.6, and the average value of cercariae shedding from infected snails were 0.0 ± 0.0,308.0 ± 96.6,428.1 ± 146.2,527.0 ± 171.1,571.4 ± 148.9,602.9 ± 356.3, respectively. In collective infection Group VII-XII,the average infection value of snails were 0 ± 0,12.3 ± 2.5,18.7 ± 4.7,28.3 ± 4.2,33.3 ± 4.7,29.3 ± 5.5,and the average fatality of snails were 22.7 ± 3.8,23.7 ± 4.5,28.3 ± 5.5,47.0 ± 9.5,75.7 ± 8.5,86.3 ± 12.2, and the average value of cercariae shedding from infected snails were 0 ± 0,244.5 ± 57.3,292.3 ± 74.8,347.1 ± 100.8,477.2 ± 142.1,447.3 ± 161.4, respectively. The second generation of artificially infected snails was obtained successfully. The average infection rate and fatality rate for the second generation of artificially infected snails were 24.65% and 24.50%, both of which were not obviously different from that of the first generation of artificially infected snails (P>0.05). In the animal experiment, the worm growth rate for the naturally infected snails, the first or second generation of artificially infected snails were 68.50%,73.50% or 71.00%. There was no obvious difference among them (P>0.05). The fecal (or liver) eggs per gram for the naturally infected snails, the first or the second generation of artificially infected snails were 1 503 ± 269,1 683 ± 233, or 1 541 ± 117 (or 6 641 ± 1 819,6 272 ± 1 419, or 7 263 ± 1 643). There was no significant difference among the 3 groups (P>0.05). CONCLUSION: Infected snails can be obtained through the artificial method by using S. Japonicum miracidia to infect snails. Individual infection has the advantage over collective infection. The optimal proportion of infection between snails and miracidia is 1:15. There was no significant difference between the first and the second generation of artificially infected snails in the average of cercariae shedding, infection, and fatality average of snails. There was no significant difference between artificially and naturally infected snails in the developmental rate of adult worms, fecal and liver eggs per gram.