Triple-negative breast cancer (TNBC) is an aggressive malignancy often characterized by chemoresistance, partly due to the overexpression of drug efflux transporters like ABCG2. To address this challenge, this study developed and evaluated a cRGD-modified, pH-sensitive liposomal system for the targeted co-delivery of docetaxel (DTX) and siRNA against ABCG2 (si-ABCG2). The synthesized nanoparticles (DTX/siRNA/cRGD-PLPs) exhibited optimal physicochemical properties, including a mean particle size of approximately 241.7 nm, efficient co-loading of DTX and siRNA, and pH-responsive cargo release, while protecting the siRNA from degradation in serum. Also, DTX/siRNA/cRGD-PLPs maintained homogeneous size distributions over the storage period and induced minimal hemoglobin release, with hemolysis rates remaining below safety threshold. These liposomes demonstrated enhanced, time-dependent uptake into TNBC cell lines HCC1937 and MDA-MB-231. In vitro, the DTX/siRNA/cRGD-PLPs formulation was significantly more effective at inhibiting cell viability, proliferation, migration, and invasion, and at inducing apoptosis, compared to the free drug combinations and other controls. Moreover, the dual-payload co-delivery liposomes (DTX/siRNA/cRGD-PLPs) exerted superior anti-tumor effects relative to single-agent formulations. In an MDA-MB-231 xenograft mouse model, the liposomal treatment was well-tolerated and resulted in marked tumor growth inhibition, which was associated with reduced cell proliferation (Ki67) and increased apoptosis (Caspase-3) within the tumor tissue. This targeted co-delivery system shows significant potential for improving TNBC treatment by synergistically enhancing therapeutic efficacy and overcoming chemoresistance.
This study aimed to investigate the serum levels and clinical significance of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in patients with early-stage breast cancer, and to evaluate its potential as a diagnostic and prognostic biomarker. In this prospective observational study, serum levels of ACSL4, inflammatory factors (CRP, IL-6, and IL-17), and tumor markers (CEA and CA153) were measured using enzyme-linked immunosorbent assay (ELISA) in 138 early-stage breast cancer patients and 115 patients with benign breast lesions. Demographic, clinical, and follow-up data were collected, and statistical analyses were performed to assess the diagnostic and prognostic value of ACSL4. Serum ACSL4 levels were significantly lower in early-stage breast cancer patients compared to those with benign breast lesions (p < 0.01). Serum ACSL4 levels showed diagnostic performance for early-stage breast cancer, with an AUC of 0.774 (95
Background The laparoscopically harvested omental flap (LHOF) has been used in partial or total breast reconstruction, but most studies on LHOF were case reports or small case series. However, the clinical feasibility and oncological safety of LHOF in oncoplastic breast surgery remains controversial. This study reported our experience applying LHOF for immediate breast reconstruction.Methods Between June 2018 and March 2022, 300 patients underwent oncoplastic breast surgery using LHOF at our institution. Their clinicopathological data, complications, cosmetic outcomes, and oncologic outcomes were evaluated.Results All patients underwent total breast reconstruction using LHOF after nipple-sparing mastectomy. The median operation time was 230 min (ranging from 155 to 375 min). The median operation time for harvesting the omental flap was 55 min (ranging from 40 to 105 min). The success rate of the laparoscopically harvested pedicled omental flap was over 99.0%. Median blood loss was 70 ml, ranging from 40 to 150 ml. The volume of the flap was insufficient in 102 patients (34.0%). The overall complication rate was 12.3%. Subcutaneous fluid in the breast area (7%) was the most common reconstruction-associated complication, but most cases were relieved spontaneously. The incidence rate of omental flap necrosis was 3.3%. LHOF-associated complications occurred in two cases, including one case of incisional hernia and one case of vascular injury. Cosmetic outcomes were satisfactory in 95.1% of patients on a four-point scale by three-panel assessment and 97.2% using the BCCT.core software. Two local and one systemic recurrence were observed during a median follow-up period of 32 months.Conclusions The LHOF for immediate breast reconstruction is a safe and feasible method that involves minimal donor-site morbidity, satisfactory cosmetic outcomes, and promising oncologic safety.
Objective:To investigate the effect of radiotherapy on breast reconstruction using the pedicled omental flap combined with a silicone implant in experimental dogs.Methods:Twenty healthy local dogs were used for the experiment. Each experimental dog underwent 2 types of breast reconstruction in anterior ventral breasts. They underwent breast reconstruction using a pedicled omental flap and a silicone implant in the left breast (the omental flap group), and prosthetic breast reconstruction only with a silicone implant in the right breast (the implant group). Four weeks after surgery, radiotherapy of the same dose was given for both breasts. Eight months after radiotherapy, the omental flap, implants and capsules were removed from the dogs. The rate of capsular contracture was compared between groups by paired χ2 test (McNemar test). The thickness of capsule and microvascular density were compared between groups by paired-samples t test.Results:The capsular contracture rate in the implant group and the omental flap group was 25.0% (5/20) and 5.0% (1/20), respectively, indicating no significant difference (χ2=2.670, P=0.219). Thickness of the capsule in the implant group was significantly higher than that in the omental flap group [ (1.4±0.2) mm vs (0.8±0.1) mm, t=4.173, P=0.001]. Microvascular density in the omental flap group was significantly higher than that in the implant group (vessels in each high power field: 44.3±5.1 vs 28.4±2.8, t=5.202, P<0.001).Conclusion:Radiotherapy shows little effect on breast reconstruction with a pedicled omental flap and a silicone implant in experimental dogs and the omentum has a protective effect on the silicone implant.
Bone metastasis of breast cancer considerably reduces not only overall survival but also health-related quality of life due to pain, fatigue, and skeletal-related events. Objective: This study aims to analyze the research hotspots and trends of global research on bone metastasis of breast cancer in the past 20 years to provide a reference for relevant personnel in this field to carry out academic research. Methods: The literature related to bone metastasis of breast cancer from 2002 to 2021 was retrieved from the Web of Science. The bibliometric research method and VOSviewer and CiteSpace were used to analyze the publications, and the research status and development direction in the last 20 years were visualized. Results: A total of 7381 articles were included. The number of global publications is increasing every year. The United States contributes the most to global research, with the most citations and the highest H-index. The journal Cancer Research published the most articles on this issue. “Macrophage” and “skeletal related event” will receive more attention and be the next popular hotspot in the future. Conclusion: There will be an increasing number of publications on bone metastasis of breast cancer based on current global trends. The United States made the largest contribution to this field. More focus will be placed on the mechanisms of metastasis research, which may be the next popular topic in bone metastasis of breast cancer.
目的:为解决传统的科研数据管理系统智能化程度低、信息难以复用等问题,设计乳腺癌临床科研数据管理系统.方法:该系统采用浏览器/服务器(Browser/Server,B/S)架构,利用ASP.NET MVC4设计,分为展示层、业务层、访问层和数据层4层,并采用Bootstrap+jQuery进行前后端交互.整个系统包括乳腺癌科研项目管理、数据管理和应用管理三大功能模块.结果:采用该系统可智能采集乳腺癌科研数据,实现对患者的乳腺癌诊断预测和生存预测.结论:该系统能够满足乳腺癌数据管理和辅助临床决策的需求,有助于更好地服务乳腺癌研究.
Breast cancer, the most prevalent malignancy in women, is also the leading cause of cancer-related deaths in women worldwide. The activation of the Wnt pathway plays a pivotal role in the metastatic abilities of breast cancer. In this study, IL1F6, MRGPRX1, and SEC14L3 were significantly correlated to breast cancer patients'overall survival based on TCGA-BRCA dataset. Although IL1F6, MRGPRX1 and SEC14L3 high expression were associated with better survival in breast cancer patients, SEC14L3 had the biggest survival benefit for breast cancer; therefore, SEC14L3 was selected for the subsequent investigation. SEC14L3 mRNA expression and protein levels within breast cancer cell lines decreased compared with normal human breast epithelial cells. Overexpressing SEC14L3 in breast cancer cells inhibited the malignant phenotypes of cancer cells, including the capacity of cells to migrate and invade. SEC14L3 overexpression decreased the levels of mesenchymal markers, whereas SEC14L3 knockdown facilitated the malignant behaviors of breast cancer cells. SEC14L3 overexpression also inhibited Wnt/β-catenin activation. The Wnt agonist strengthened the malignant phenotypes of breast cancer cells; moreover, the anti-tumor effects of SEC14L3 overexpression were partially attenuated by the Wnt agonist. Conclusively, SEC14L3, which is underexpressed in breast cancer cells and tissues, could play a tumor-suppressive role in a Wnt/β-catenin-related way.
Background: Pertuzumab plus trastuzumab combined with chemotherapy has become a standard neoadjuvant therapy option for patients with high-risk human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). There is still not enough evidence for the efficacy and safety of neoadjuvant pertuzumab and trastuzumab plus chemotherapy in HER2-positive BC patients in China, both in clinical trials and real-world settings. This study aimed to assess the efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy in Chinese patients with HER2-positive BC in real-world clinical application. Methods: We retrospectively collected the data from the electronic medical records of HER2-positive patients treated with neoadjuvant trastuzumab and pertuzumab plus chemotherapy from December 2018 to May 2021 at 21 hospitals located in Hunan Province, China, including age, American Joint Committee on Cancer (AJCC) stage, clinical tumor size, clinical lymph node status, pathological characteristics (before neoadjuvant systemic therapy), treatment approach, adverse events to neoadjuvant therapy, and achievement of pathological complete response (pCR). The primary endpoint was the total rate of pCR, and the secondary endpoints were the rate of pCR of each subgroup and the safety of dual anti-HER2 therapy. Results: A total of 188 patients met the inclusion criteria and were included in the analysis. Of the 188 patients, 119 (63.3%) were diagnosed at stage II and 64 (34.0%) at stage III; 163 (86.7%) were cT2-3; 149 patients (79.3%) were >= cN1; 84 patients (44.7%) were hormone receptor (HR)-positive. pCR was observed in 88 of 188 patients (46.8%). The pCR rate of HR-negative patients (54.8%) was higher (P=0.014) than that of HR-positive patients (36.9%). Patients with Ki-67 <15% achieved a higher (P=0.033) pCR rate (68.2%) than those with Ki-67 >= 15% (44.0%). Anemia was the most common adverse event (63.4%), and the most common grade 3-4 adverse event was nausea and vomiting (8.5%). Conclusions: Our study confirmed the benefit of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy on pCR with a tolerable safety profile in routine clinical practice in Chinese patients with HER2-positive BC. HR-negativity and Ki-67 <15% were associated with pCR in these patients.
The administration of doxorubicin (DOX) is one of the first-line treatments of breast cancer. However, acquisition of resistance remains the major obstacle restricting the clinical application of DOX. MicroRNAs (miRNAs) are small, noncoding RNAs which play crucial role in epigenetic regulation. Recent studies have shown that miRNAs are associated with tumor chemoresistance. Here we aim to explore the role of miRNA-192-5p in resistance to DOX in breast cancer cells. Normal human breast epithelial cell line MCF-10A, breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), and DOX-resistant breast cancer cell line MCF-7/ADR were used here. The expression of miR-192-5p was examined by qPCR, and the expression of peptidylprolyl isomerase A (PPIA) was examined by qPCR and Western blot. The effects of miR-192-5p overexpression on the sensitivity to DOX were confirmed by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and Annexin-V/PI assay. Downstream molecular mechanisms, including PPIA, BAD, CASP9, Bcl-2, and c-Jun N-terminal kinase (JNK) activation, were detected by Western blot and qPCR. Luciferase reporter assay was used to validate the association between miR-192-5p and PPIA. miR-192-5p was downregulated while PPIA was upregulated in MCF-7/ADR cells. Functionally, miR-192-5p overexpression increased sensitivity to DOX by promoting cell apoptosis. Mechanistically, miR-192-5p overexpression performed its function by activating JNK, augmenting BAD and caspase9 expression, and suppressing Bcl-2 and PPIA expression. Luciferase assay validated that PPIA was a direct target of miR-192-5p. miR-192-5p sensitizes breast cancer cells to DOX by targeting PPIA, suggesting that miR-192-5p might serve as a novel target for reversing DOX resistance and controlling breast tumor growth.
OBJECTIVE:To explore the clinical application of the pedicled omentum flap in breast reconstruction of breast cancer patients. METHODS:Between May 2013 and October 2017, 205 patients with breast cancer received modified mastectomy. The pedicled omentum flap was used to reconstruct breast at the same time. All patients were female with an average age of 34.9 years (mean, 26-58 years). The tumor located at left breast in 127 cases and right side in 78 cases. The diameter of the tumor was 2-5 cm (mean, 2.9 cm). The 120 cases of breast cancer were at stage Ⅰ and 85 cases were at stage Ⅱ; and 126 cases were invasive ductal carcinoma and 79 cases were invasive lobular carcinoma. The course of disease ranged from 10 to 92 days (mean, 38.5 days). The size of defect after tumor ablation ranged from 9 cm× 6 cm to 18 cm×12 cm; the size of pedicled omentum flap ranged from 18 cm×10 cm to 22 cm×16 cm. RESULTS:According to the anatomical basis, the omentum was divided into 4 types, including thin type (42 cases, 20.5%), medium type (133 cases, 64.9%), hypertrophy type (24 cases, 11.7%), and absence type (6 cases, 2.9%). All omentum flaps survived successfully and the incisions healed by first intention. All patients were followed up 6-74 months (mean, 24.5 months); 83 cases were followed up more than 5 years. The shape, texture, and elasticity of the reconstructed breast were good and no flap contracture deformation happened. Only linear scar left at the donor sites, and the function of abdomen was not affected. No local recurrence happened. CONCLUSION:The pedicled omentum flap can be harvested safely and reliable, which is the one of ideal option for breast reconstruction in breast cancer patients.
Objective To analyze the clinicopathologic features and prognosis of low-age young breast cancer patients (age ≤30 years old). Methods 138 low-age young patients pathologically confirmed as breast cancer who received radical surgery in our hospital from January 1992 to December 2005 were selected, 206 middle and old age breast cancer patients (age >35 years old) during the same period were randomly selected as control. The clinicopathologic characteristics were compared between the two groups. The Kaplan-Meier method was used to analyze the survival of breast cancer patients in different age groups. Results Compared with the control group, large lump and positive lymph node metastasis were more common in the low-age young group, with statistically significant differences (P<0.05). The 5 year survival rates of low-age young group and the control group were 66.7% and 78.7%, the 10 year survival rates were 47.1% and 56.0%. Kalpan-Meleir survival analysis showed that the overall survival of the two groups were significantly different. Conclusion The low-age young patients with breast cancer are with inferior biological behavior, such as larger lump, higher lymph node metastasis, and poor prognosis. Therefore, early diagnosis and early treatment should be advocated in clinical practice, and more attention should be paid to very young patients to improve the prognosis. Key words: Young breast cancer; Clinicopathologic characteristics; Prognosis
Surgery is the mainstay of breast cancer treatment.Additionally,the standard management of breast cancer now can include adjuvant systemic therapy and radiotherpy.On the basis of oncological safety, the original shackles of breast-conserving surgery are unceasingly broken.And oncoplastic breast-conserving surgery has become the complementary form of original breast-conserving surgery.Conservative mastectomy is the extension of the concept of breast-conserving surgery.Breast reconstructive surgery breeds new hope, even if for those patients who have contraindication for breast-conserving surgery or have fears about breast-conserving surgery.The formation of modern medical model promotes the combination of medical scientism and humanism.According to this idea, the purpose of medical treatment must be associated with the needs of patients.And the treatment of diseases should be combined with improvements of the quality of life.Developments in surgical treatment of breast cancer are affected by modern medical model, under which patients begin to pay attention to the quality of life and doctors begin to satisfy the medical therapy and life quality for patients.
Modem biopsychosocial medical model embodies the organic combination of medical scientism and humanism.It emphasizes the necessity of humanistic care in medical practice.This kind of humanistic care includes not only cating for people,but also caring for technology.Because of humanistic care,itis necessary to realize the improvement of technology.Patients get benefits from the progress for humanistic care.PICC,one of intravenous infusion system,can provide the protective effect to peripheral vein,but is still visible.Venous access port can be completely hidden in the body of patients,maximize the protection of the privacy of the patient.At the same time,the interference of daily life is greatly reduced,the complication rate is reduced,the quality of life of patients increases significantly.Therefore,by using the venous access port in patients with breast cancer,its humanities spirit is revealed from the design concept and the actual use of the process and effect.
目的 探讨MRI与彩超在评价局部晚期乳腺癌新辅助化疗临床效果中的作用. 方法 选取我院收治局部晚期乳腺癌患者63例为研究对象,患者采取新辅助化疗,化疗降期后采取手术治疗,依照手术方法不同分为保乳术组和改良根治术组,改良根治术组行全乳切片病理检查,保乳术组行乳腺切缘、乳头切缘及瘤床病理切片并与化疗前后影像学变化进行比较. 结果 MRI、彩超测得肿瘤最大径与病理误差较少,MRI与病理测得值关联性最好,MRI测得的肿瘤最大径与病理测得值误差小于彩超.患者术后病理体积大小为(9.65±2.84)mm3,与化疗后肿瘤MRI体积大小(9.62±2.37) mm3比较,无明显差异(P>0.05),术后病理体积大小显著小于化疗前肿瘤MRI体积,(41.62 ±56.27)mm3(P<0.05). 结论 局部晚期肿瘤乳腺癌患者采用MRI诊断能够较高地评估肿瘤形态,与彩超相比,能够更加准确地为新辅助化疗方案的疗效评价提供依据.
目的:探讨乳管镜在诊治未扪及肿块乳头溢液中的应用价值.方法:收集2015年1-10月笔者所在医院119例非哺乳期未扪及肿块的乳头溢液患者的临床资料,总结乳管镜在诊疗乳头溢液患者中的作用.结果:95例(79.8%)患者发现了乳管内肿物,其中诊断为导管内乳头状瘤50例,导管扩张并炎症23例,乳腺增生11例,导管内癌11例.结论:乳管镜检查为未扪及肿块乳头溢液病因诊断的首选方法,对乳腺癌的早期发现有重要价值.
目的 探讨腹腔镜下游离带蒂大网膜在保乳术中的应用效果. 方法 选择湖南省肿瘤医院(中南大学湘雅医学院附属肿瘤医院)乳腺外二科2013年5月至2014年5月收治的早期乳腺癌患者8例,行保乳术,术中行腹腔镜下游离带蒂大网膜修复乳房缺损. 结果 7例患者术后网膜瓣均全部成活,乳房自然柔软外观形态良好,患者十分满意;1例在行腔镜下网膜游离时,网膜与左下腹壁粘连,游离时损伤网膜血管弓,只保留下部分网膜组织,因网膜瓣组织量少修复乳房外形欠佳. 结论 早期乳腺癌保乳术中行腹腔镜下游离带蒂大网膜乳房成形术为一种安全、微创的手术,腹腔镜下获得大网膜瓣的并发症发生率较低,可作为有效的技术在临床中应用.
Objective To discuss the feasibility and effect of immediate breast reconstruction with pedicled greater omentum and gel prosthesis following nipple and areola complex sparing mastectomy. Methods From August 2013 to September 2015, after mastectomy with conservation of nipple and areola, twenty-three patients with stage 0,Ⅰ,Ⅱbreast cancer accepted immediate breast reconstruction with pedicled greater omentum and gel prosthesis. Results All the pedicled greater omentum was successfully inserted, and no prosthesis migration and rupture occurred 3 to 25 months after operations. The reconstructed breast was good in shape and with soft feeling. Nipple ischemia occurred in two patients with ductal carcinoma in situ, while skin necrosis was not found within 3 months. There was no recurrence of breast cancer during follow-up period. Conclusion Immediate breast reconstruction with pedicled greater omentum and gel prosthesis after mastectomy with conservation of nipple and areola is an effective and safe procedure.
目的:探讨麦默通微创旋切系统在临床诊断和治疗不可触及乳腺肿块中的应用。方法:收集我科自2014年9月~2015年9月麦默通手术患者的临床资料,总结其临床经验。结果:188例患者的乳腺肿块均被安全的切除,术后有13例患者出现血肿或硬结,有2例患者出现皮下瘀斑,术后随访均未出现肿瘤的残留与复发。结论:麦默通旋切系统在不可触及乳腺肿物的治疗中具有定位精准、创伤小、安全性高及术后美观等优点,值得临床广泛应用。
Cisplatin resistance presents a major challenge in the successful treatment of breast cancer, and its mechanism has not been documented well. In this study, to determine the relationship between chemotherapy resistance and microRNA (miRNA) expression during the development of cisplatin resistance in breast cancer, we used microRNA microarrays analysis successfully identified 19 miRNAs that were either overexpressed or underexpressed (8 upregulated and 11 downregulated) in the MCF-7 cell line and its cisplatin-resistant variant MCF-7/DDP. Among them, the miR-218 was most downregulated in cisplatin-resistant cell lines and identified that breast cancer 1 (BRCA1) was the cellular targets of miR-218. In vivo assay also demonstrated that restoring miR-218 expression in MCF-7/DDP cell line could sensitize cells against cisplatin, thereby increasing cisplatin-mediated tumor cell apoptosis and reducing DNA repair. Kaplan-Meier survival analysis indicated that patients with breast cancer display high levels of miR-218 and low levels of BRCA1 expression; these patients may gain the greatest benefits in terms of increased survival when treated with cisplatin. All of these results indicated that miR-218 has a significant function in the development of cisplatin resistance in breast cancer. Restoring miR-218 expression may constitute a novel therapeutic approach by which to increase cisplatin sensitivity in breast cancer.
Objective:To explore the curative effects of infraclavicula lymph node dissection via pectoralis approach in the treatment of breast cancer. Method:86 cases were divided into the observation group(n=43) and the control group(n=43) according to the random number table.The control group was given conventional surgery with electric scalpel,while the observation group was given infraclavicula lymph node dissection via pectoralis approach.The two groups of patients were compared for operation time,volume of drainage,intraoperative blood loss and complications.Result:The observation group had significantly shorter operation time,more volume of drainage and less intraoperative blood loss than the control group,with statistical differences(P<0.05);and the incidence of complications in the observation group was significantly lower than the control group,with statistical difference(P<0.05).Conclusion:For patients with breast cancer,infraclavicula lymph node dissection via pectoralis approach combined with Auchincloss can thoroughly remove the lymph nodes with shorter operation time,more volume of drainage,less intraoperative blood loss and fewer complications.