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With the rapid development of the field of life sciences, traditional 2D cell culture and animal models have long been unable to meet the urgent needs of modern biomedical research and new drug development. Establishing a new generation of experimental models and research models is of great significance for deeply understanding human health and disease processes, and developing effective treatment measures. As is well known, long research and development cycles, high risks, and high costs are the "three mountains" facing the development of new drugs today. Organoids and organ-on-chips technology can highly simulate and reproduce the human physiological environment and complex reactions in vitro, greatly improving the accuracy of drug clinical efficacy prediction, reducing drug development costs, and avoiding the defects of drug testing animal models. Therefore, organ-on-chips have enormous potential in medical diagnosis and treatment.
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Dispositivos Lab-On-A-Chip , Organoides , Humanos , Animais , Sistemas MicrofisiológicosRESUMO
Purpose: We prospectively analyzed the correlation between fasting plasma glucose (FPG) and the risk of breast cancer in women; explored the independent risk factors for breast cancer in women, and compared the effect of FPG level on the risk of young and non-young breast cancer. Our study provides new evidence and ideas for research into breast cancer etiology in China, improves the accuracy of secondary prevention of breast cancer, and provides options for the clinical diagnosis and treatment of breast cancer patients with diabetes. Materials and methods: Three cohorts of women participating in the first health examination of the Kailuan Group in 2006, 2008 and 2010 were assembled to conduct a descriptive analysis of the baseline data on FPG. The cumulative incidence of breast cancer in different groups over 13 years was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A Cox proportional hazards regression model was used to analyze the association between FPG level and the risk of breast cancer. Results: The cumulative incidence of breast cancer increased in people with FPG higher than 5.29 mmol/L, but there was no significant difference in the effect of different levels of FPG on the risk of young breast cancer in the population. Different degrees of fasting glucose can affect the risk of non-young breast cancer in the population. Conclusion: The results of this study suggest that the risk of breast cancer can be reversed by early intervention to control levels of FPG. Regular monitoring of FPG may reduce the misdiagnosis rate of breast cancer in the population.
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Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA. METHODS: Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. RESULTS: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. CONCLUSIONS: n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.
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Doença das Coronárias , Ácidos Graxos Ômega-3 , Estudos Observacionais como Assunto , Humanos , Ácidos Graxos Ômega-3/sangue , Doença das Coronárias/sangue , Doença das Coronárias/prevenção & controle , Doença das Coronárias/epidemiologia , Feminino , Estudos Retrospectivos , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Estudos Prospectivos , Suplementos Nutricionais , Idoso , Fatores de RiscoRESUMO
Background: There is an interest in performing de-escalating axillary surgery after neoadjuvant chemotherapy (NAC). However, the significance of residual axillary node disease after NAC has not been well studied. Objectives: To investigate the pathological residual axillary lymph node tumor burden (ypN) of patients with initial clinical nodal stage cN0-1 breast cancer after NAC and determine its prognostic value. Design: Initial cN0-1 breast cancer patients who received NAC followed by axillary surgery at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University between January 2011 and December 2019 were included. Methods: Survival outcomes were compared according to different clinical and pathological stage and nodal response to NAC. The main outcomes were disease-free survival (DFS) and overall survival (OS). Factors associated with survival were defined by Cox regression analysis. Results: A total of 911 patients were included, among whom 260 had cN0 and 651 had cN1 tumors. After NAC, 410 patients were ypN0, and another 501 were ypN+. The median follow-up time was 63 months. There was no significant difference in DFS or OS between the cN0 and cN1 groups in hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+) and HR-/HER2- subtypes; instead, ypN status was significantly related to DFS and OS. In HR+/HER2- subtype, both cN and ypN stages did not show significant survival differences, but the ypN number and the nodal response to NAC showed significant prognostic value (p < 0.05). Among HR-/HER2+ patients, all cN status, ypN status, ypN number, and nodal response were significantly associated with survival (p < 0.05). Furthermore, tumor biology, axillary surgery, ypN status, pathological tumor size, and radiotherapy were independent prognostic factors for DFS and OS. Conclusion: The ypN status after NAC provide more prognostic information than the initial cN stage in cN0-1 patients, and the surgical axillary staging after NAC may have high clinical value.
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[This corrects the article DOI: 10.1016/j.isci.2024.109057.].
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BACKGROUND: High-grade B-cell lymphoma (HGBL) is an unusual malignancy that includes myelocytomatosis viral oncogene (MYC), B-cell lymphoma-2 (BCL-2), and/or BCL-6 rearrangements, termed double-hit or triple-hit lymphomas, and HGBL-not otherwise specific (HGBL-NOS), which are morphologically characteristic of HGBL but lack MYC, BCL-2, or BCL-6 rearrangements. HGBL is partially transformed by follicular lymphoma and other indolent lymphoma, with few cases of marginal zone lymphoma (MZL) transformation. HGBL often has a poor prognosis and intensive therapy is currently mainly advocated, but there is no good treatment for these patients who cannot tolerate chemotherapy. CASE SUMMARY: We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression. Gene analysis revealed the gene expression profile was identical in the pre- and post-transformed tissues, suggesting that the two diseases are homologous, not secondary tumors. The chemotherapy was ineffective and the side effect was severe, so we tried combination therapy including venetoclax and obinutuzumab. The patient tolerated treatment well, and reached partial response. The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure. He survived for 12 months after diagnosis. CONCLUSION: Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients, who are unsuitable for chemotherapy.
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Purpose: This 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. Methods: The 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. Results: In 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. Conclusion: We 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.
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The liver is a major metabolic organ of the human body and has a high incidence of diseases. In recent years, the annual incidence of liver disease has increased, seriously endangering human life and health. The study of the occurrence and development mechanism of liver diseases, discovery of new therapeutic targets, and establishment of new methods of medical treatment are major issues related to the national economy and people's livelihood. The development of stable and effective research models is expected to provide new insights into the pathogenesis of liver diseases and the search for more effective treatment options. Organoid technology is a new in vitro culture system, and organoids constructed by human cells can simulate the morphological structure, gene expression, and glucose and lipid metabolism of organs in vivo, providing a new model for related research on liver diseases. This paper reviews the latest research progress on liver organoids from the establishment of cell sources and application of liver organoids and discusses their application potential in the field of liver disease research.
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Hepatopatias , Fígado , Organoides , Medicina Regenerativa , Organoides/metabolismo , Humanos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/terapia , Hepatopatias/metabolismo , Hepatopatias/patologia , Animais , Medicina Regenerativa/métodos , Modelos Biológicos , Regeneração HepáticaRESUMO
Enabling materials to undergo reversible dynamic transformations akin to the behaviors of living organisms represents a critical challenge in the field of material assembly. The pursuit of such capabilities using conventional materials has largely been met with limited success. Herein, the discovery of reversible constrained dissociation and reconfiguration in MXene films, offering an effective solution to overcome this obstacle is reported. Specifically, MXene films permit rapid intercalation of water molecules between their distinctive layers, resulting in a significant expansion and exhibiting confined dissociation within constrained spaces. Meanwhile, the process of capillary compression driven by water evaporation reinstates the dissociated MXene film to its original compact state. Further, the adhesive properties emerging from the confined disassociation of MXene films can spontaneously induce fusion between separate films. Utilizing this attribute, complex structures of MXene films can be effortlessly foamed and interlayer porosity precisely controlled, using only water as the inducer. Additionally, a parallel phenomenon has been identified in graphene oxide films. This work not only provides fresh insights into the microscopic mechanisms of 2D materials such as MXene but also paves a transformative path for their macroscopic assembly applications in the future.
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BACKGROUND: Some Chinese scholars have initially explored the efficacy of electroacupuncture at Baliao acupoint in patients with functional anorectal pain (FAP). However, their studies are performed in a single center, or the sample size is small. Therefore, we aim to further explore the efficacy of electroacupuncture at Baliao acupoint on the treatment of FAP. METHODS: In this multicenter randomized controlled trial, 136 eligible FAP patients will be randomly allocated into an electroacupuncture group or sham electroacupuncture group at a 1:1 ratio. This trial will last for 34 weeks, with 2 weeks of baseline, 4 weeks and 8 weeks of treatment, and 1, 3, and 6 months of follow-up. Outcome assessors and statisticians will be blind. The primary outcome will be clinical treatment efficacy, and secondary outcomes will be pain days per month, quality of life, psychological state assessment, anorectal manometry, pelvic floor electromyography, and patient satisfaction. DISCUSSION: Results of this trial will be contributed to further clarify the value of electroacupuncture at Baliao acupoint as a treatment for FAP in the clinic. TRIAL REGISTRATION: This trial has been registered in Chinese Clinical Trial Registry https://www.chictr.org.cn/ (ChiCTR2300069757) on March 24, 2023.
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Eletroacupuntura , Adulto , Feminino , Humanos , Masculino , Canal Anal/fisiopatologia , Manejo da Dor/métodos , Medição da Dor , Satisfação do Paciente , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Reto/fisiopatologia , Resultado do TratamentoRESUMO
Triple-negative breast cancer (TNBC) has attracted attention due to its poor prognosis and limited treatment options. The mechanisms underlying the association between circular RNAs (circRNAs) and the occurrence and development of TNBC remain unclear. CircZCCHC2 is observed to be upregulated in TNBC cells, tissues, and plasma exosomes. Knockdown of circZCCHC2 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of TNBC cells in vitro and in vivo. Pirarubicin (THP) treatment downregulated circZCCHC2, and circZCCHC2 affected the sensitivity to THP. CircZCCHC2/miR-1200/translocated promoter region, the nuclear basket protein (TPR) pathway was cascaded and verified. It is demonstrated that circZCCHC2 plays a crucial role in the malignant progression of TNBC via the miR-1200/TPR axis, thereby activating the RAS-RAF-MEK-ERK pathway. The present results indicate that circZCCHC2 has the potential to serve as a novel prognostic biomarker for TNBC.
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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+ï¼breast cancer patients following neoadjuvant therapyï¼NATï¼. 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.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Metástase Linfática/patologia , Terapia Neoadjuvante , Estudos Retrospectivos , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Linfonodos/patologia , Axila/patologiaRESUMO
BACKGROUND: Banxia Xiexin decoction (BXD) is a traditional Chinese medicine with anti-colorectal cancer (CRC) activity. However, its bioactive constituents and its mechanism of action remain unclear. Herein, we explored the mechanism of action of BXD against CRC using a network pharmacology approach. METHODS: First, the targets of the main chemical components of BXD were predicted and collected through a database, and the intersection of compound targets and disease targets was obtained. Subsequently, protein-protein interaction network analysis, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the potential mechanisms underlying the effects of BXD on CRC. Finally, a CRC cell model and a CRC xenograft model in nude mice were utilized to further determine the mechanism of action. RESULTS: A compound-therapeutic target network of BXD was constructed, revealing 146 cellular targets of BXD. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling axis was identified as the main target of BXD. Using in vitro and in vivo models, the activity of BXD against CRC was found to be mediated through ferritinophagy by targeting the PI3K/AKT/mTOR axis, leading to intracellular iron accumulation, reactive oxygen species activation, and finally ferroptosis. CONCLUSIONS: Through the application of network pharmacology and in vitro/in vivo validation experiments, we discovered that BXD exerts anti-CRC effects via the ferritinophagy pathway. Furthermore, we elucidated the potential mechanism underlying its induction of ferritinophagy. These findings demonstrate the significant potential of traditional drugs in managing CRC and support their wider clinical application in combination chemotherapy, targeted therapy, and immunotherapy.
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Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Animais , Camundongos , Humanos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Camundongos Nus , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Fosfatidilinositol 3-Quinase , Serina-Treonina Quinases TOR , Neoplasias Colorretais/tratamento farmacológico , Simulação de Acoplamento Molecular , MamíferosRESUMO
BACKGROUND: The widespread use of vaccines against the novel coronavirus disease (COVID-19) has become one of the most effective means to establish a population immune barrier. Patients with cancer are vulnerable to COVID-19 infection, adverse events, and high mortality, and should be the focus of epidemic prevention and treatment. However, real-world data on the safety of vaccines for patients with breast cancer are still scarce. OBJECTIVE: This study aims to compare the safety of COVID-19 vaccines between patients vaccinated before or after being diagnosed with breast cancer. METHODS: Patients with breast cancer who sought medical advice from October 2021 to December 2021 were screened. Those who received COVID-19 vaccines were enrolled in this study to analyze the safety of the vaccines. The primary outcome was patient-reported adverse events (AEs). All events after vaccine injection were retrospectively documented from the patients. RESULTS: A total of 15,455 patients with breast cancer from 41 hospitals in 20 provinces in China were screened, and 5766 patients who received COVID-19 vaccines were enrolled. Of those enrolled, 45.1% (n=2599) of patients received vaccines before breast cancer diagnosis, 41.3% (n=2379) were vaccinated after diagnosis, and 13.6% (n=784) did not known the accurate date of vaccination or cancer diagnosis. Among the patients vaccinated after diagnosis, 85.4% (n=2032) were vaccinated 1 year after cancer diagnosis and 95.4% (n=2270) were vaccinated during early-stage cancer. Of all 5766 vaccinated patients, 93.9% (n=5415) received an inactivated vaccine, 3.7% (n=213) received a recombinant subunit vaccine, and 2.4% (n=138) received other vaccines, including adenovirus and mRNA vaccines. In the first injection of vaccines, 24.4% (n=10, 95% CI 11.2-37.5) of patients who received an adenovirus vaccine reported AEs, compared to only 12.5% (n=677, 95% CI 11.6-13.4) of those who received an inactivated vaccine. Patients with metastatic breast cancer reported the highest incidence of AEs (n=18, 16.5%, 95% CI 9.5-23.5). Following the second injection, patients who received an inactivated vaccine (n=464, 8.7%, 95% CI 8.0-9.5) and those who received a recombinant vaccine (n=25, 8.7%, 95% CI 5.5-12.0) reported the same incidence of AEs. No significant differences in patient-reported AEs were found between the healthy population and patients with breast cancer (16.4% vs 16.9%, respectively); the most common AEs were local pain (11.1% vs 9.1%, respectively), fatigue (5.5% vs 6.3%, respectively), and muscle soreness (2.3% vs 3.6%, respectively). The type of vaccine and time window of vaccination had little impact on patient-reported AEs. CONCLUSIONS: Compared with patients vaccinated before breast cancer diagnosis, there were no significant differences in patient-reported AEs in the patients vaccinated after diagnosis. Thus, it is safe for patients with breast cancer, especially for those in the early stage, to receive COVID-19 vaccines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200055509; https://tinyurl.com/33zzj882.
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Neoplasias da Mama , COVID-19 , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Vacinas contra COVID-19/efeitos adversos , Estudos Transversais , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação/efeitos adversos , China/epidemiologia , Vacinas de Produtos InativadosRESUMO
Various novel HER2-targeted antibody-conjugated drugs (ADCs) have shown satisfactory antitumor activity in HER2-low-positive breast cancer (BC). It is urgent to clarify whether HER2-low-positive tumors have unique biological behavior and should be considered a new molecular subtype. We screened eligible BC patients and collected relevant information at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2020. A total of 1027 patients were included in our study cohort, and 66.0% (678/1027) had HER2-low-positive tumors. Compared to HER2-zero patients, HER2-low-positive patients tended to have more lymph node metastasis, a larger proportion of hormone receptor (HR)-positive tumors, and a lower proliferation rate (Ki-67). The pathologic complete response (pCR) rate of HER2-low-positive patients was lower than that of HER2-zero patients (19.3% vs 26.1%), especially in the HR-positive subgroup (12.00% vs 20.29%). However, multivariate logistic regression analysis showed that HER2 status was not an independent factor for predicting pCR. HER2-low-positive patients had a higher overall survival (OS) rate in the HR-positive subgroup. The Cox regression model analysis suggested that HER2-low-positive status did not statistically significantly affect the survival outcomes, regardless of disease-free survival (DFS) (P=0.308) or OS (P=0.066). In conclusion, HER2-low-positive tumors have unique clinical and pathological characteristics, with a lower pCR rate in the HR-positive subgroup and better survival in the HR-negative subgroup compared to HER2-zero tumors. However, the effect of HER2-low-positive status on pCR or survival outcomes was not statistically significant.
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PURPOSE: This study aimed to develop and evaluate triptolide nanoemulsion gels (TP-NE gels) as a transdermal drug delivery system. METHODS: TP-NE was prepared and optimized via emulsification and the central composite design response surface method. The optimized TP-NE gel was evaluated in vitro and in vivo. TP-NE gel microstructure, in vitro and in vivo pharmacokinetics, and anti-rheumatoid arthritis effects were studied to evaluate the feasibility of its percutaneous administration. RESULTS: The Optimized TP-NE was observed using a Malvern Autosizer Nano ZS 90 inspection system and a transmission electron microscope (TEM). The nanoemulsion had an average size of 162.9 ± 0.281 nm, a polydispersity index of 0.272 ± 0.024, a zeta potential of -30.03 ± 2.01 mV, and mostly spherical and uniform morphology. In addition, the TP-NE gel pharmacokinetics, assessed via a skin-blood two-site synchronous microdialysis, revealed that TP was higher in the skin than in the blood. TP-NE gel is crucial in reducing knee edema, inhibiting inflammation, and treating rheumatoid arthritis by regulating tumor necrosis factor-alpha, interleukin-1ß, and -6 levels. CONCLUSION: The TP-NE gel is a promising local delivery method for rheumatoid arthritis (RA)-associated edema and inflammation and can serve as a prospective platform for percutaneous TP administration.
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Circular RNAs (circRNAs) have been found to be involved in cancer progression and chemotherapy sensitivity. However, the biological function of circRNAs in triple-negative breast cancer (TNBC) and its effect on the sensitivity to pirarubicin (THP) chemotherapy are still unclear. CircEGFR (hsa_circ_0080220) was screened and verified by bioinformatics analysis, proving it was highly expressed in TNBC cell lines, patient tissues, and plasma exosomes, and was associated with poor prognosis of patients. The expression level of circEGFR in patient tissue has potential diagnostic value to distinguish TNBC tissue from normal breast tissue. In vitro studies confirmed that overexpression of circEGFR promoted the proliferation, migration, invasion, and EMT of TNBC cells and decreased the sensitivity of THP treatment while silencing circEGFR showed the opposite effect. The circEGFR/miR-1299/EGFR pathway was cascaded and verified. CircEGFR regulated malignant progression of TNBC by regulating EGFR via sponging miR-1299. THP can inhibit the malignant phenotype of MDA-MB-231 cells by downregulating the expression of circEGFR. In vivo studies confirmed that overexpression of circEGFR can promote tumor growth and EMT and reduce tumor sensitivity to THP treatment. Silencing circEGFR inhibited the malignant progression of the tumor. These results revealed circEGFR is a promising biomarker for TNBC diagnosis, therapeutic and prognosis.
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MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , RNA Circular/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
Importance: Breast cancer treatment has profoundly improved in China recently. However, trends in disparities and transitions of treatment in early-stage cancer between China and the US are not well known. Objective: To identify changes for patients with early breast cancer by using large databases from China and the US. Design, Setting, and Participants: This multicenter cross-sectional study used the Chinese Society of Clinical Oncology Breast Cancer (CSCO BC) database from hospitals in 13 provinces in China and the Flatiron Health (hereinafter referred to as Flatiron) database from more than 280 community oncology clinics in the US. Patients with stage I to III breast cancer diagnosed from January 1, 2011, to December 31, 2021, were included. Data were analyzed from June 10 to December 1, 2022. Main Outcomes and Measures: The distribution of age, clinical stage, and cancer subtypes at diagnosis were examined overall and by year. The mean annual percent change (MAPC) from 2011 to 2021 in systemic therapy and surgery was also analyzed. Results: A total of 57â¯720 patients with early breast cancer were screened from the CSCO BC (n = 45â¯970) and Flatiron (n = 11â¯750) databases. The median age at diagnosis in China among the 41 449 patients included in the age analysis was 47 (IQR, 40-56) years; in the US, the median age was 64 (IQR, 54-73) years. Among patients with clinical stage data in the CSCO BC (n = 22 794) and Flatiron (n = 4413) databases, the proportion of stage I cancer was 7250 (31.8%) vs 2409 (54.6%); stage II cancer, 10 043 (44.1%) vs 1481 (33.6%); and stage III cancer, 5501 (24.1%) vs 523 (11.9%). The proportion of hormone receptor-positive cancer in China was 69.8%, lower than that in the US (87.5%). For patients with ERBB2 (formerly HER2 or HER2/neu)-positive cancer, the proportion in China (30.2%) was higher than that in the US (15.6%). For neoadjuvant therapy, the annual rate increased from 247 of 1553 (15.9%) to 200 of 790 (25.3%) in China, with an MAPC of -4.4% (95% CI, -50.6% to 85.0%; P = .89). For patients with ERBB2-positive cancer, the proportion treated with trastuzumab in early-stage cancer in China increased significantly, with an MAPC of 22.1% (95% CI, 17.4%-26.9%; P < .001), and overtook that in the Flatiron database since 2017 (1684 [68.5%] vs 550 [62.5%]; P < .001). Conclusions and Relevance: The findings of this cross-sectional study suggest that disparities in treatment of early breast cancer narrowed between China and the US during the study period. The rapid growth of trastuzumab treatment in China was suggestive of differential access to targeted ERBB2 therapy.
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Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Adulto , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Estudos Transversais , Trastuzumab , Terapia Neoadjuvante , China/epidemiologiaRESUMO
Breast cancer is now the most common cancer worldwide, and it is also the main cause of cancer-related death in women. Survival rates for female breast cancer have significantly improved due to early diagnosis and better treatment. Nevertheless, for patients with advanced or metastatic breast cancer, the survival rate is still low, reflecting a need for the development of new therapies. Mechanistic insights into metastatic breast cancer have provided excellent opportunities for developing novel therapeutic strategies. Although high-throughput approaches have identified several therapeutic targets in metastatic disease, some subtypes such as triple-negative breast cancer do not yet have an apparent tumor-specific receptor or pathway to target. Therefore, exploring new druggable targets in metastatic disease is a high clinical priority. In this review, we summarize the emerging intrinsic therapeutic targets for metastatic breast cancer, including cyclin D-dependent kinases CDK4 and CDK6, the PI3K/AKT/mTOR pathway, the insulin/IGF1R pathway, the EGFR/HER family, the JAK/STAT pathway, poly(ADP-ribose) polymerases (PARP), TROP-2, Src kinases, histone modification enzymes, activated growth factor receptors, androgen receptors, breast cancer stem cells, matrix metalloproteinases, and immune checkpoint proteins. We also review the latest development in breast cancer immunotherapy. Drugs that target these molecules/pathways are either already FDA-approved or currently being tested in clinical trials.