Prognostic factors and adjuvant systemic therapy for patients with HER2-positive T1N0 breast cancer: evidence from a real-world study with long-term follow-up.

PURPOSE: The optimal adjuvant systemic treatment and potential prognostic factors for patients with T1N0 HER2-positive breast cancer are still unclear. We conducted a real-world study in this relatively low-risk population to identify the clinical-pathological factors of potential prognostic value and to compare the efficacy of different adjuvant strategies. METHODS: We included patients with HER2-positive T1N0 breast cancer of infiltrating ductal carcinoma (IDC) histology treated at the Cancer Hospital, Chinese Academy of Medical Sciences from April 2010 to April 2017. We performed Cox multivariate analysis to identify the potential prognostic factors for invasive disease-free survival (IDFS). We also compared survival outcomes of (1) patients treated with adjuvant chemotherapy alone, or chemotherapy plus trastuzumab, or observation; (2) patients receiving adjuvant anthracycline-based and non-anthracycline regimens, both combined with trastuzumab. Inverse probability of treatment weighting (IPTW) propensity score was used to reduce selection bias. RESULTS: Overall, 692 consecutive patients were included, with a median follow-up of 78.0 months for IDFS. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab were identified as independent prognostic factors. For adjuvant treatment, compared with observation and chemotherapy alone, chemotherapy plus trastuzumab could significantly benefit patients (HR = 2.70, P = 0.034; HR = 3.95, P < 0.001). Meanwhile, compared with observation, chemotherapy alone did not significantly benefit patients (HR = 1.37, P = 0.424). For the comparison of anthracycline-based versus non-anthracycline regimens when combined with trastuzumab, patients in both groups had similar IDFS (HR = 1.74, P = 0.242). CONCLUSIONS: HER2-positive T1N0 IDC patients could benefit from adjuvant chemotherapy plus trastuzumab. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab are independent prognostic factors for this population.

Evaluation of a beneficial effect of adjuvant chemotherapy in patients with stage I triple-negative breast cancer: a population-based study using the SEER 18 database.

PURPOSE: To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). METHODS: TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. RESULTS: A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51-0.90; OS, HR = 0.54, 95% CI 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16-0.95; OS, HR = 0.41, 95% CI 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52-0.88) and OS (HR = 0.54, 95% CI 0.44-0.66) than the patients who did not receive chemotherapy. CONCLUSION: According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.

Prognosis prediction and risk stratification of breast cancer patients based on a mitochondria-related gene signature.

As the malignancy with the highest global incidence, breast cancer represents a significant threat to women's health. Recent advances have shed light on the importance of mitochondrial function in cancer, particularly in metabolic reprogramming within tumors. Recognizing this, we developed a novel risk signature based on mitochondrial-related genes to improve prognosis prediction and risk stratification in breast cancer patients. In this study, transcriptome data and clinical features of breast cancer samples were extracted from two sources: the TCGA, serving as the training set, and the METABRIC, used as the independent validation set. We developed the signature using LASSO-Cox regression and assessed its prognostic efficacy via ROC curves. Furthermore, the signature was integrated with clinical features to create a Nomogram model, whose accuracy was validated through clinical calibration curves and decision curve analysis. To further elucidate prognostic variations between high and low-risk groups, we conducted functional enrichment and immune infiltration analyses. Additionally, the study encompassed a comparison of mutation landscapes and drug sensitivity, providing a comprehensive understanding of the differing characteristics in these groups. Conclusively, we established a risk signature comprising 8 mitochondrial-related genes-ACSL1, ALDH2, MTHFD2, MRPL13, TP53AIP1, SLC1A1, ME3, and BCL2A1. This signature was identified as an independent risk predictor for breast cancer patient survival, exhibiting a significant high hazard ratio (HR = 3.028, 95%CI 2.038-4.499, P < 0.001). Patients in the low-risk group showed a more favorable prognosis, with enhanced immune infiltration, distinct mutation landscapes, and greater sensitivity to anti-tumor drugs. In contrast, the high-risk group exhibited an adverse trend in these aspects. This risk signature represents a novel and effective prognostic indicator, suggesting valuable insights for patient stratification in breast cancer.

Predictive Value of the Neutrophil-Lymphocyte Ratio for Tumor Regression Grade and Prognosis of Local Advanced Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy.

PURPOSE: Numerous indicators can be used to predict tumor patients' prognosis and tumor regression grade (TRG). The role of the neutrophil-lymphocyte ratio (NLR) among individuals with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) hasn't been studied, nevertheless. This study aims to explore the predictive value of the NLR before nCRT (pre-NLR) in TRG and prognosis of LARC patients undergoing nCRT.. METHODS: In this retrospective investigation, 326 LARC patients receiving nCRT in total were included. The link between the pre-NLR and TRG was examined using a logistic regression analysis. A Cox-based nomogram was created in the meanwhile to forecast overall survival (OS). With the use of calibration plots and receiver operating characteristic (ROC) curves, we evaluated the nomogram's predictive capabilities. RESULTS: The median pre-NLR across 326 patients was 2.2 (interquartile range, IQR: 1.7-2.7). In the logistic regression analysis, only the pre-NLR for TRG in LARC patients receiving nCRT was statistically significant (odds ratio, OR = 0.62, 95% CI: 0.47-0.80, P < 0.001). Pre-NLR, nCRT with surgery interval, ypTNM stage, TRG, vascular invasion, adjuvant chemotherapy, and carbohydrate antigen 19-9 before nCRT were revealed to be OS predictors in the Cox multivariate analysis. According to calibration plots and ROC curves, the predictive nomogram demonstrated high statistical performance on internal validation. CONCLUSION: This study demonstrated that a lower pre-NLR was probably associated with a greater rate of TRG in LARC patients undergoing nCRT. Furthermore, the pre-NLR was credibly correlated with OS in LARC patients undergoing nCRT. Meanwhile, we constructed a nomogram for predicting the prognosis in LARC patients undergoing nCRT.

Differences in clinical characteristics and prognosis between breast neuroendocrine carcinoma and breast invasive ductal carcinoma: A multicentre population-based study from China.

AIM: We constructed a multicentre cohort in China to analyse the differences in clinical characteristics, treatment strategies and prognoses between breast neuroendocrine carcinoma (NEC) and invasive ductal carcinoma (IDC) of the breast. METHODS: All patients with early-stage breast cancer who attended three hospitals in Beijing from 2000 to 2018 were included in the study. We used propensity score matching to make a 1:3 match between NEC and IDC. RESULTS: After propensity score matching, 153 patients with IDC and 51 patients with NEC were analysed. Multivariate Cox regression showed that compared to patients with IDC, patients with NEC had a worse disease-free survival (HR = 2.94, 95% CI: 1.69-5.12, p < 0.001). CONCLUSION: NEC patients have a worse disease-free survival than IDC patients.

Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis.

Background: HER2-low expression breast cancer (BC) accounts for approximately 45%-55% of all BC cases. The purpose of this study was to investigate the prognostic difference between patients with HER2-low expression and HER2-zero BC. Methods: An electronic search of Pubmed, Embase, Cochrane Library, and Web of Science databases was performed to screen studies that included prognostic comparisons between HER2-zero and HER2-low expression groups. A total of 14 studies involving 52106 patients were included. Results: Our results indicated that HER2-low expression was associated with a significant benefit in OS among all patients with early BC (HR, 0.83; 95% CI, 0.78-0.88), patients with hormone-receptor positive BC (HR, 0.83; 95% CI, 0.77-0.89), and patients with TNBC (HR, 0.78; 95% CI, 0.70-0.87). HER2-low expression was associated with a significant benefit in DFS among all patients (HR, 0.81; 95% CI, 0.71-0.93), patients with hormone receptor-positive BC (HR, 0.81; 95% CI, 0.72-0.90), but no significant difference in DFS was found in patients with TNBC (HR, 0.87; 95% CI, 0.65-1.17). HER2-low expression was associated with a significant benefit in RFS among all patients (HR, 0.90; 95% CI, 0.85-0.95), patients with hormone receptor-positive BC (HR, 0.90; 95% CI, 0.84-0.96), but no significant difference in RFS was found in patients with TNBC (HR, 0.80; 95% CI, 0.55-1.16). Conclusions: Among patients with early-stage BC, patients with HER2-low expression BC had better OS in the overall population, hormone receptor-positive and TNBC subgroups. Besides, favorable DFS and RFS were observed in both the overall population and hormone receptor-positive subgroup. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD 42022349458).

A novel non-invasive exhaled breath biopsy for the diagnosis and screening of breast cancer.

BACKGROUND: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. METHODS: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. RESULTS: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. CONCLUSIONS: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Prognostic Value of Copy Number Alteration Burden in Early-Stage Breast Cancer and the Construction of an 11-Gene Copy Number Alteration Model.

The increasing burden of breast cancer has prompted a wide range of researchers to search for new prognostic markers. Considering that tumor mutation burden (TMB) is low and copy number alteration burden (CNAB) is high in breast cancer, we built a CNAB-based model using a public database and validated it with a Chinese population. We collected formalin-fixed, paraffin-embedded (FFPE) tissue samples from 31 breast cancer patients who were treated between 2010 and 2014 at the National Cancer Center (CICAMS). METABRIC and TCGA data were downloaded via cBioPortal. In total, 2295 patients with early-stage breast cancer were enrolled in the study, including 1427 in the METABRIC cohort, 837 in the TCGA cohort, and 31 in the CICAMS cohort. Based on the ROC curve, we consider 2.2 CNA/MBp as the threshold for the CNAB-high and CNAB-low groupings. In both the TCGA cohort and the CICAMS cohort, CNAB-high had a worse prognosis than CNAB-low. We further simplified this model by establishing a prognostic nomogram for early breast cancer patients by 11 core genes, and this nomogram was highly effective in both the TCGA cohort and the CICAMS cohort. We hope that this model will subsequently help clinicians with prognostic assessments.

Epidemiology of occupational dermatoses associated with personal protective equipment use in the COVID-19 pandemic: Risk factors and mitigation strategies for frontline health care workers.

Background: Personal protective equipment (PPE)-related occupational dermatosis (PROD) represents a significant occupational burden to health care workers (HCWs), and understanding its epidemiology is imperative in formulating mitigation strategies. Objectives: To determine the prevalence of PROD in HCWs, characterize its manifestations, identify its risk factors, and evaluate behavioral modifications of HCW. Methods: A cross-sectional study using an online questionnaire was conducted from July to September 2020. HCWs who had direct contact with COVID-19 patients for a minimum of 2 weeks cumulatively were invited to participate. Results: The prevalence of PROD among 416 valid respondents was 73.8% (307/416), with face masks being the most common cause (93.8% [n = 288]). The most common PROD associated with face masks, protective eyewear, hairnets, gowns, and gloves were acne (71.5% [206/288]), pressure-related injuries (70.7% [99/140]), scalp itch (53.3% [16/30]), itch/rash (78.8% [26/33]), and xerosis (75.0% [27/36]), respectively. Exposure to PPE beyond an hour increased the odds of PROD by 4.8-fold. The majority of HCWs made behavioral modifications to mitigate PROD. Conclusions: We underscore evidence-based recommendations for HCWs to be (1) scheduled hourly breaks from PPE wear, (2) fitted to various PPE models, (3) screened for preexisting dermatoses before deployment, and (4) educated on mitigation strategies and avenues for help should they encounter PROD.

Prognostic factors of primary neuroendocrine breast cancer: A population-based study.

BACKGROUND: Primary neuroendocrine breast carcinomas (NEBCs) are an extremely rare and underrecognized subtype of mammalian carcinoma. The prognostic factors for NEBCs remain controversial. METHODS: In this multicenter retrospective study, the prognostic factors for patients with primary NEBCs who underwent surgery and had a pathologically confirmed diagnosis of neuroendocrine carcinoma in China and the United States were examined. The endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 51 Chinese patients and 98 US patients were included. In the Chinese cohort, tumor grade and Ki-67 levels were prognostic factors for DFS in univariate analysis (hazard ratio [HR] = 5.11 [1.67-15.60], p = 0.004; HR = 57.70 [6.36-523.40], p < 0.001, respectively) and multivariate analysis (HR = 100.52 [1.33-7570.21], p = 0.037; HR = 31.47 [1.05-945.82], p = 0.047, respectively). In the US cohort, age was an important prognostic factor for OS in univariate analysis (HR = 1.09 [1.04-1.15], p = 0.001). The random effects model for the combined cohorts revealed age and positive expression of estrogen receptor (ER) as potential prognostic factors for OS (HR = 1.08 [1.01-1.14], p = 0.015; HR = 0.10 [0.02-0.44], p = 0.003, respectively). CONCLUSIONS: Tumor grade and Ki-67 levels are important prognostic factors for DFS of patients with primary NEBCs. Age and ER status are important prognostic factors for OS of patients with primary NEBCs.

Efficacy and Safety of Epirubicin Combined with Temozolomide for Treatment of Advanced Leiomyosarcoma.

BACKGROUND: Leiomyosarcoma (LMS) accounts for 24% of all soft tissue sarcomas (STSs) and this STS subtype has high metastatic potential. Previous studies indicated the best median progression-free survival (mPFS) time was 9.2 months and the best overall response rate (ORR) was 30.9%. We evaluated the efficacy and safety of epirubicin combined with temozolomide (EPI-TMZ) for treatment of advanced LMS. METHODS: This was a retrospective review of the records of patients with advanced LMS at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. All patients initiated EPI-TMZ treatment between January 2018 and December 2020. RESULTS: We examined 15 patients who received EPI-TMZ for LMS. This was a first-line treatment in 6 patients, a second- or third-line treatment in 7 patients, and a fourth-line treatment in 2 patients. At the time of data cutoff (April 25, 2021), the median PFS was 10 months, 1 patient had clinical complete response (cCR), 7 had partial response (PR), and 7 had stable disease (SD). The overall response rate (ORR) was 53.3% (8/15) and the disease control rate (DCR) was 100.0% (15/15). The most common treatment-related adverse effects were leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, and oral mucositis. One patient had severe adverse effect (febrile neutropenia), but there were no treatment-related deaths. CONCLUSION: EPI-TMZ is potentially effective for treatment of advanced LMS, and the adverse effects appear tolerable. EPI-TMZ provided better outcomes than reported in previous studies of other treatments for advanced LMS.

Design, synthesis and antibacterial activity of novel andrographolide derivatives.

A series of andrographolide derivatives were synthesized through a facile condensation reaction with different carboxylic acids. The new compounds were characterized and screened for their antibacterial activities. A number of the new compounds significantly reduced bacterial quorum sensing virulence factors production in Pseudomonas aeruginosa, essential for pathogenesis. Compound 11b showed the best activity among all the new compounds.

Screening-based and Risk-based Strategy for the Prevention of Early-onset Group B Streptococcus/Non-group B Streptococcus Sepsis in the Neonate: A Systematic Review and Meta-analysis.

BACKGROUND: Screening-based and risk-based strategies are the 2 strategies for preventing group B streptococcus (GBS) diseases in neonates. We aimed to compare the effects of these 2 strategies in reducing the incidence of early-onset GBS sepsis (GBS-EOS) and their effects on the incidence of non-GBS sepsis. METHODS: PubMed, Embase, Web of Science and The Cochrane Central Register of Controlled Trials were searched for the period from January 1, 1996, to December 31, 2018. Randomized controlled trials and cohort studies that compared the effects of risk-based and screening-based strategies were eligible for the meta-analysis. The I statistic was used for assessing the statistical heterogeneity across studies. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: There were 18 cohort studies comparing the incidence of GBS-EOS between the 2 strategies, involving a total of 604,869 newborns and 791 GBS-EOS cases. The heterogeneity across studies was moderate (I = 45%), and the pooled analysis yielded a 55% decreased risk of GBS-EOS for screening-based versus risk-based strategy (RR = 0.45; 95% CI: 0.34-0.59). For total early onset non-GBS sepsis (non-GBS-EOS), 7 studies with low heterogeneity (I = 18%) had a pooled RR of 0.91 (95% CI: 0.74-1.11), whereas for ampicillin resistant Escherichia coli-EOS, a subgroup of non-GBS-EOS, 3 studies with very low heterogeneity (I = 0%) had a pooled RR of 1.28 (95% CI: 0.74-2.21) for screening-based strategy compared with risk-based strategy. CONCLUSIONS: Compared with risk-based strategy, screening-based prophylaxis was associated with a reduced risk of GBS-EOS.

A Review on Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris (PRP) is an idiopathic, papulosquamous inflammatory dermatosis. It is characterized by hyperkeratotic follicular papules coalescing into orange-red scaly plaques, islands of sparing, and palmoplantar keratoderma. PRP can be subdivided into six clinical subtypes according to Griffiths' classification, based on age of onset, disease extent, prognosis, and other associated features. The sixth subtype of PRP occurs in individuals affected by HIV infection, and retroviral screening in all de novo cases of PRP is advised. Other reported associations include various infections, autoimmunity, drugs, and malignancies, although the true significance of these is still unclear. The genetic basis for familial cases, most commonly categorized under the fifth subtype, has been mapped to gain of function mutations in the caspase recruitment domain family, member 14 (CARD14) gene. Treatment of PRP remains a challenge to this day due to a paucity of high-quality evidence. Therapeutic regimens have been guided mostly by case reports and case series, with the mainstay of treatment being oral retinoids. Recently, biologics have emerged as a promising treatment for PRP. We present a review of the clinicopathologic features, pathogenesis, associated disorders, and treatment of PRP, with an emphasis and critical appraisal of the existing literature on the latter.

Septic arthritis in immunocompetent and immunosuppressed hosts.

Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases.

Design, synthesis, and preliminary cardioprotective effect evaluation of danshensu derivatives.

A series of (R)-3,4-dihydroxyphenyllactic acid Danshensu (DSS) derivatives were synthesized, and their cardioprotective effects were evaluated in vitro and in vivo. Among the new derivatives, compound 14 showed significant protective effects in cultured myocardial cells and in the rat model of myocardial ischemia. The therapeutic efficacy of compound 14 was significantly higher than that of its parent compound DSS, and amlodipine, a first-line treatment for angina pain. Compound 14 potently scavenged free radicals, significantly decreased the levels of LDH and MDA, and inhibited the leakage of CK in animal model of ischemia. We had previously found that compound 14 activated PI3K/Akt/GSK-3ß and Nrf2//Keap1/heme oxygenase-1 (HO-1) signaling pathways in H9c2 cells. These results suggest that compound 14 has a unique mechanism of action, that is, multifunctional. Compound 14 may be a new potential therapy for ischemic heart diseases.