BackgroundChemotherapy resistance is the main obstacle to breast cancer recurrence, metastasis, and mortality. Drug-tolerant persister (DTP) cells are a novel type of target cell associated with tumor resistance, and autophagy is a key factor in maintaining the survival of tumor DTP cells. However, it is unclear whether the activation of autophagy in breast cancer DTP cells is related to their overexpression of the transcriptional regulatory factor CDCA7.MethodsWe analyzed CDCA7 expression using public datasets and clinical samples and established breast cancer cell lines with CDCA7 overexpression and knockdown to assess the role of CDCA7 in breast cancer. Autophagy was assessed via electron microscopy, mRFP-GFP-LC3 imaging, and immunoblotting. Mechanistic studies employed ChIP-seq, dual-luciferase assays, and site-directed mutagenesis. Functional assays measured chemosensitivity (CCK-8), migration/invasion (scratch/Transwell), and in vivo tumorigenicity (mouse xenograft).ResultsCDCA7 was significantly upregulated in breast cancer DTP cells. Overexpression of CDCA7 in breast cancer cells significantly enhanced autophagy-related biological processes and molecular functions. Through ChIP-seq and targeted knockout experiments, we identified the binding sites of CDCA7 on the autophagy-related protein genes ULK1, ATG2A, and ATG3. Using transmission electron microscopy and mRFP/mCherry-GFP-LC3B tandem fluorescent tagging, we observed that CDCA7 knockdown significantly reduced the number of autolysosomes in breast cancer DTP cells and markedly inhibited autophagic flux. Moreover, CDCA7 knockdown not only decreased drug resistance in breast cancer cells but also reduced metastasis, invasion, and tumorigenic ability in vivo, ultimately prolonging the survival of tumor-bearing mice.ConclusionCDCA7 drives breast cancer chemoresistance by transcriptionally activating a pro-survival autophagy program in DTP cells, nominating it as a promising therapeutic target.
Purpose To examine the mediating role of social support in the relationship between fear of cancer recurrence (FCR) and fertility intention among reproductive-aged women with breast cancer. Methods This study employed a cross-sectional design, utilising convenience sampling to select 231 women of reproductive-aged diagnosed with breast cancer and treated at a tertiary hospital in Chongqing between December 2023 and June 2024 as research subjects.Participants completed a demographic questionnaire, the Fertility Intention Scale, the Social Support Rating Scale, and the Fear of Progression Questionnaire-Short Form (FoP-Q-SF).Pearson correlation analysis was conducted to examine the inter-variable correlations, followed by the construction of a structural equation model using AMOS 26 software, with bootstrap method applied to verify the mediation effects. Results Fertility intention was negatively correlated with FCR (r = -0.610, P < 0.001) and positively correlated with social support (r = 0.673, P < 0.001). Social support was also negatively correlated with FCR (r = -0.521, P < 0.001). Structural equation modeling revealed that social support partially mediated the relationship between FCR and fertility intention, accounting for 27.93% of the total effect. Conclusion Enhancing social support may help alleviate FCR and subsequently increase fertility intention among reproductive-aged women with breast cancer.
BACKGROUND:The lncRNA growth arrest-specific 5 (GAS5) is involved in regulating breast cancer progression. In this study, we aimed to elucidate the function and mechanism of GAS5 in breast cancer.METHODS:The expressions of GAS5, fat mass and obesity-associated protein (FTO), insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and Quaking (QKI) were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. The m6A modification level of GAS5 was detected using m6A immunoprecipitation assay (MeRIP). The interaction between IGF2BP2 and GAS5 or QKI was detected using RNA immunoprecipitation assay (RIP) and dual luciferase reporter assay. Cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) assay. The biological functions of the FTO/GAS5/IGF2BP2/QKI axis was assessed using the tumor xenograft assay.RESULTS:LncRNA GAS5 expression decreased in breast cancer and was regulated by FTO-mediated m6A modification in an IGF2BP2-dependent manner, resulting in decreased GAS5 stability and expression. GAS5 recruited IGF2BP2 to target QKI and upregulated QKI expression in breast cancer cells. GAS5 suppressed breast cancer growth via IGF2BP2/QKI, and this inhibitory effect was modulated by FTO both in vitro and in vivo.CONCLUSIONS:GAS5 regulated by FTO-mediated m6A modification represses the growth of breast cancer via the IGF2BP2/QKI pathway, suggesting that the FTO/GAS5/IGF2BP2/QKI pathway can be a potential target for breast cancer treatment.
乳腺癌是女性最常见的恶性肿瘤,且发病率仍呈逐年上升趋势,严重威胁女性的身心健康[1,2]。癌症患者的随访是临床以及科研工作中必不可少的部分[3]。对癌症患者的随访可以了解其出院后的生存状态、远期疗效、肿瘤的复发、转移等信息,对随访数据的分析总结有助于加深对疾病发生、发展、治疗以及预后的认识,从而更好地协助临床和科研工作[3]。此外,在随访的同时,也可以加强医患之间的沟通,从而更好地提升临床服务质量[4]。伴随着临床综合治疗水平的提高,乳腺癌患者的生存期显著延长[5,6],因此,乳腺癌患者的随访是一个长期的过程,如何完成持续、有效的随访是提高随访率的关键。笔者总结2004年1月至2014年12月在陆军军医大学第一附属医院乳腺甲状腺外科手术治疗的5 139例乳腺癌患者随访情况,分析影响术后随访率的因素,为进一步高效开展随访工作提供参考。
IntroductionBreast cancer is a common malignant tumor associated with high morbidity and mortality. The role of ferroptosis, a regulated form of cell death, in breast cancer development and prognosis remains unclear. This study aims to investigate the relationship between ferroptosis-related genes and breast cancer and develop a prognostic model.MethodsRNA-seq expression datasets and clinical samples of breast cancer patients were obtained from public databases. Immunity- and drug resistance-related data were integrated. A preliminary screening was performed, resulting in the identification of 73 candidate ferroptosis factors. Univariate Cox regression analysis was conducted to select 12 genes, followed by LASSO Cox regression analysis to construct a prognostic risk prediction model consisting of 10 ferroptosis-related genes. The model was further characterized by immune cell infiltration. The expression levels of ferroptosis-related genes were validated in human breast cancer cell lines, and immunohistochemical (IHC) analysis was conducted on cancer specimens to assess ferroptosis-related protein expression.Results:The study identified 10 ferroptosis-related genes that were significantly associated with breast cancer prognosis. The constructed prognostic risk prediction model showed potential for predicting the prognostic value of these genes. In addition, the infiltration of immune cells was observed to be a characteristic of the model. The expression levels of ferroptosis-related genes were confirmed in human breast cancer cell lines, and IHC analysis provided evidence of ferroptosis-related protein expression in cancer specimens.DiscussionThis study provides a novel prognostic model for breast cancer, incorporating 10 ferroptosis-related genes. The model demonstrates the potential for predicting breast cancer prognosis and highlights the involvement of immune cell infiltration. The expression levels of ferroptosis-related genes and proteins further support the association between ferroptosis and breast cancer development.
甲状腺癌发病率居我国恶性肿瘤第7位,居我国女性恶性肿瘤第3位[1].过去的30年里,甲状腺癌的发病率增加了300%[2],其中以甲状腺乳头状癌(papil-lary thyroid carcinoma,PTC)为主.PTC是甲状腺癌最常见的组织学亚型,占新发病例的80%~85%[3].
Background:Early diagnosis of breast cancer has always been a difficult clinical challenge. We developed a deep-learning model EDL-BC to discriminate early breast cancer with ultrasound (US) benign findings. This study aimed to investigate how the EDL-BC model could help radiologists improve the detection rate of early breast cancer while reducing misdiagnosis. Methods:In this retrospective, multicentre cohort study, we developed an ensemble deep learning model called EDL-BC based on deep convolutional neural networks. The EDL-BC model was trained and internally validated on B-mode and color Doppler US image of 7955 lesions from 6795 patients between January 1, 2015 and December 31, 2021 in the First Affiliated Hospital of Army Medical University (SW), Chongqing, China. The model was assessed by internal and external validations, and outperformed radiologists. The model performance was validated in two independent external validation cohorts included 448 lesions from 391 patients between January 1 to December 31, 2021 in the Tangshan People's Hospital (TS), Chongqing, China, and 245 lesions from 235 patients between January 1 to December 31, 2021 in the Dazu People's Hospital (DZ), Chongqing, China. All lesions in the training and total validation cohort were US benign findings during screening and biopsy-confirmed malignant, benign, and benign with 3-year follow-up records. Six radiologists performed the clinical diagnostic performance of EDL-BC, and six radiologists independently reviewed the retrospective datasets on a web-based rating platform. Findings:The area under the receiver operating characteristic curve (AUC) of the internal validation cohort and two independent external validation cohorts for EDL-BC was 0.950 (95% confidence interval [CI]: 0.909-0.969), 0.956 (95% [CI]: 0.939-0.971), and 0.907 (95% [CI]: 0.877-0.938), respectively. The sensitivity values were 94.4% (95% [CI]: 72.7%-99.9%), 100% (95% [CI]: 69.2%-100%), and 80% (95% [CI]: 28.4%-99.5%), respectively, at 0.76. The AUC for accurate diagnosis of EDL-BC (0.945 [95% [CI]: 0.933-0.965]) and radiologists with artificial intelligence (AI) assistance (0.899 [95% [CI]: 0.883-0.913]) was significantly higher than that of the radiologists without AI assistance (0.716 [95% [CI]: 0.693-0.738]; p < 0.0001). Furthermore, there were no significant differences between the EDL-BC model and radiologists with AI assistance (p = 0.099). Interpretation:EDL-BC can identify subtle but informative elements on US images of breast lesions and can significantly improve radiologists' diagnostic performance for identifying patients with early breast cancer and benefiting the clinical practice. Funding:The National Key R&D Program of China.
BACKGROUND:Minimally invasive (robotic or laparoscopic-assisted) nipple-sparing mastectomy combined with prosthesis breast reconstruction (NSM-PBR) is associated with smaller scars and greater patient satisfaction. However, the oncological safety of minimally invasive NSM-PBR remains controversial.PATIENTS AND METHODS:This was a retrospective study of patients with breast cancer who underwent breast reconstruction between 1 January 2006 and 20 February 2021. Demographic and clinicopathological characteristics, operation information, postoperative complications, and survival outcomes were analyzed.RESULTS:In all, 292 patients underwent minimally invasive NSM-PBR and 205 underwent open NSM-PBR for breast cancer. In the minimally invasive NSM-PBR group, 268 (91.8%) patients underwent laparoscopy and 24 (8.2%) patients underwent robot-assisted NSM-PBR. Mean operation time in the minimally invasive NSM-PBR group was significantly longer than that in the open NSM-PBR group (P = 0.023). Mean intraoperative blood loss was significantly less in the minimally invasive NSM-PBR group (P < 0.05). There was no significant between-group difference in total complications. Similarly, there were no significant between-group differences in overall survival, recurrence-free survival, and local recurrence rate (P = 0.450, P = 0.613, and P = 0.679, respectively).CONCLUSIONS:The complication, recurrence, and mortality rates in minimally invasive NSM-PBR group were comparable to those in open NSM-PBR group. Our preliminary results are encouraging and suggest that minimally invasive NSM-PBR affords good cosmetic results and its oncological safety is comparable to that of open surgery.
Background:Epigenetic modification of chromatin is an important step in the regulation of gene expression. The chromobox family proteins (CBXs), as epigenetic modifier, may play a vital role in tumorigenesis and cancer progression. Herein we explored the correlation between CBXs and breast cancer (BC) via the bioinformatics approach and qRT-PCR validation.Methods:Several databases, including GEPIA, TCGA, GEO, K-M plotter, STRING, DAVID, cBioPortal, CIBERSORT, and HPA were employed to analyze the expression levels of CBXs and the correlations between CBXs and prognosis (overall and recurrence-free survival) in BC. We analyzed molecular functions, genetic variations, transcription factors of CBXs, and immune cell infiltration status. ROC curve analysis was performed to determine the predictive value of CBXs. RNA extracted from 11 human BC and paired adjacent normal tissues were subjected to qRT-PCR.Results:The mRNA expression level of CBX1-5 was significantly upregulated, while that of CBX7 was significantly downregulated in BC; no expression disparities were observed in CBX6/8 expression. Further, high mRNA expression of CBX1/2/3/4/8 correlated with advanced BC, whereas high mRNA expression of CBX6/7 correlated with early BC. High mRNA expressions of CBX1/2/3/5 predict poor OS and RFS, while higher mRNA expressions of CBX6/7 predict better OS and RFS in patients with BC. ROC curve analysis revealed that CBX3 showed excellent discriminatory ability. Gene ontology enrichment analysis showed that CBXs primarily participated in SUMOylation and post-/transcriptional regulation. Moreover, they presented varying degrees of amplification in BC tissues and were related to the infiltration of various immune cells.Conclusion:CBXs can serve as putative biomarkers for BC. Further studies are warranted to determine the exact molecular mechanisms underlying the action of CBXs in BC, particularly CBX1/2/3/5/7.
Background Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. Methods The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. Results Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment ( P adjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827−0.997) was achieved in the integrated model. Conclusions Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.
Purpose: Chemoresistant cells are pre-existing and adaptively selected by chemotherapy. The biomarkers of chemoresistant cells in luminal breast cancer remain unknown. The expression of CD44 and CD24 are associated with breast cancer progression. This study aimed to explore the proportion change of differently expressed CD44/CD24 tumor cells during the induction of chemoresistance. Methods: Tumor specimens of patients with luminal breast cancer resistant and sensitive to chemotherapy drugs regimens were collected. The proportion of CD44+/−CD24+/− tumor cells in the two groups of samples was compared by immunofluorescence staining. MCF-7 and T47D variants resistant to chemotherapy drugs were induced by pulse selection of the parental cells with the IC90 value of the two drugs for 7 weeks. Changes in the proportion of CD44+/−CD24+/− cells during the induction of chemoresistance were observed and compared using flow cytometry. Results: The proportion of CD44+CD24+ cells in the tumor tissues of chemoresistant patients was significantly higher than chemosensitive patients. At the endpoint of chemoresistance induction, the proportions of CD44+CD24+ cells reached 86.27%, 84.41%, 83.03%, and 85.12% in MCF-7/EPI, MCF-7/DOC, T47D/EPI, and T47D/DOC, respectively. The proportion of CD44+CD24− cells increased briefly and then decreased to nearly the pre-induction level (3.01%). The proportion of CD44−CD24− and CD44−CD24+ cells in the four chemoresistant variants was less than 5% at the endpoint of chemoresistance induction. Conclusions: The enrichment of CD44+CD24+ cells predicts chemoresistance in luminal breast cancer. CD44+CD24+ is a biomarker for chemoresistant luminal breast cancer cells.
Objective To investigate the clinical characteristics and influencing factors of insomnia in perimenopausal women based on polysomnography (PSG). Methods A total of 52 perimenopausal women admitted to our psychological clinic due to insomnia were included in this study. According to the results of Pittsburgh sleep quality index (PSQI), they were divided into study group (PSQI≥7) and control group (PSQI < 7). Sleep status was recorded by polysomnography (PSG), and symptoms related to perimenopausal period were measured by menopause rating scale (MRS).The differences of PSG monitoring sleep-related indicators and MRS results were compared between the 2 groups, and the correlations of each sleep indicator with perimenopausal symptoms were analyzed. Results ① The total sleep time and sleep efficiency were significantly decreased in the perimenopausal women from the study group than those from the control group (P < 0.05). The former group had obviously longer sleep latency and wakefulness time when compared with the latter group (P < 0.05). ② These perimenopausal women had the clinical feature of rapid eye movement (REM) sleep behavior, which were characterized by decreased total time of REM sleep, decreased proportion of REM sleep, prolonged latency of REM sleep, and increased frequency of REM to wakefulness in the study group when compared with the control group (P < 0.05). ③The total MRS score, somatic symptom score, psychological symptom score and genitourinary system score were 26.69±5.13, 9.49±2.92, 10.34±2.95 and 6.86±2.89, respectively, in the study group, which were all higher than those of the control group (P < 0.05). ④The proportion of REM sleep and the total time of REM sleep were negatively correlated with depression (P < 0.05), while the latency of REM sleep was positively correlated with anxiety and sexual life quality (P < 0.05). Conclusion Insomnia in perimenopausal women is characterized by REM sleep disorder, and REM sleep is closely related to anxiety, depression and sexual life quality.
2019 年12 月以来,以湖北省武汉市为中心,全国各省市、自治区、新疆生产建设兵团以及境外陆续出现了多例新型冠状病毒肺炎(简称新冠肺炎)患者. 该病毒潜伏期长、传染性强. 截止2020年2月26日24时,全国累计确诊患者78497例,累计死亡患者2744例,疑似患者及累计追踪到密切接触者652174例[1]. 疫情之下,陆军军医大学第一附属医院乳腺甲状腺外科全体医护人员积极响应号召,参照国家、军队以及重庆市相关政策法规及规章制度及时制定并发布了《新型冠状病毒肺炎疫情期间乳腺疾病患者诊治流程管理》[2]、《新型冠状病毒肺炎疫情下乳腺癌日间化疗病房运行管理实践》[3]等一系列乳腺疾病管理流程. 工作人员严格执行这些管理流程,基本保障了需来院手术、化疗和靶向治疗等患者的需求,实现了在科学防控的基础上最大限度保证肿瘤患者诊治的目的[4].
Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype and lacks targeted therapies. Trametes robiniophila Murr (Huaier) has been widely used in clinical anti-cancer treatments in China. Previously, we found that Huaier can effectively improve 5-year overall survival and disease free survival in stage III TNBC patients. The Polysaccharides of Huaier (PS-T) were identified as the major components of Huaier. Further study will be needed to elucidate the efficacy of PS-T as potential anti-tumor adjuvant strategy in TNBC. Methods: Transwell assay, scratch assay and mice lung metastasis model were used to observe cell invasion and migration in vitro and in vivo. Western blotting was used to determine the expression of epithelial-mesenchymal transition (EMT) and autophagy related proteins. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and protein expression of LC3 and Snail. A cell line MDA-MB-231-siATG5 in which autophagy key protein ATG5 was stably interfered was constructed. An E-cadherin promoter reporter gene plasmid and a Snail overexpression plasmid were sequentially introduced into MDA-MB-231 cells. Immunohistochemistry and Database analysis online(the Human Protein Atlas, UALCAN, Kaplan-Meier plotter) were used to explore the distinct prognostic and potential therapeutic value of Snail in breast cancer patients. Findings: PS-T inhibited cell invasion and migration in vitro and in vivo, and reversed the EMT while induced autophagy. Utilization of autophagy inhibitor LY294002 or knockdown of ATG5 by lentivirus infection suppressed the inhibitory effects of PS-T. Snail, a key transcription factor that controls EMT initiation was found to be degraded by PS-T induced autophagy. Overexpression of Snail reversed the inhibitory effects of PS-T. IHC for breast cancer tissues of 33 cases of TNBC patients and Database analysis online verified that high expression of Snail was associated with poor prognostics. Interpretation: We demonstrate that PS-T can inhibit EMT in breast cancer cell by the induction of autophagy to degrade Snail protein which contributes to both the EMT and metastasis. This study provides a new insight into the mechanism by which PS-T reduce the recurrence of TNBC and new ideas for comprehensive treatment strategies for TNBC patients. Funding Statement: National Natural Science foundation of China (No. 81802664).Declaration of Interests: All authors declare no competing interest.Ethics Approval Statement: Animals were treated according to protocols established by the ethics committee of Army Medical University and the experiments in vivo were conducted according to the approved guidelines and approved by the ethics committee of Army Medical University (AMUWEC2019199).
目的 分析乳腺癌改良根治术后女性患者的心理健康状况,探讨其与患者人格的关系.方法 采用横断面调查研究的方式,纳入2018年9~12月在陆军军医大学第一附属医院乳腺甲状腺外科接受过乳腺癌改良根治术后到门诊或住院部复查的女性患者132例.采用汉密尔顿焦虑量表(HAMA)及汉密尔顿抑郁量表-24(HAMD-24)测定患者的焦虑和抑郁情绪,采用乳腺癌患者生活质量量表(FACT-B)评估患者术后生活质量,用中文版10项目大五人格量表(TIPI-C)评估患者的人格特质.用Spearman相关性分析探讨乳腺癌术后女性患者的HAMA和HAMD-24评分与患者的年龄、术后时间、文化水平的相关性.用Mann-Whitney U检验对比≤50岁组与>50岁组的各个量表评分.生活质量和人格各因素对HAMA、HAMD-24评分的影响采用多重线性回归分析.人格各因素对生活质量的影响也采用多重线性回归分析.结果 患者年龄为(48±9)岁,最大年龄69岁,最小年龄32岁.术后时间为(5±2)个月,范围1~12个月.132例患者中,130例存在焦虑情绪(HAMA评分≥7分),占98.5%,111例存在抑郁情绪(HAMD-24评分≥7分),占84.1%.焦虑情绪与患者的年龄及术后时间呈负相关(r=-0.244、-0.313,P=0.005,P<0.001).≤50岁组与>50岁组患者在HAMA评分、FACT-B的附加关注和TIPI-C的开放性方面差异有统计学意义(Z=-3.142、-2.794、-2.286,P均<0.050).患者术后焦虑情绪的影响因素包括情感状况、生理状况、开放性、神经质性(B=-1.986,95%CI:-3.158~-0.814,t=-3.354,P=0.001;B=-1.765,95%CI:-2.853~-0.678,t=-3.211,P=0.002;B=-0.510,95%CI:-0.796~-0.223,t=3.515,P=0.001;B=-0.425,95%CI:-0.804~-0.046,t=-2.219,P=0.028),而抑郁情绪的影响因素包括情感状况及生理状况(B=-4.123,95%CI:-5.272~-2.974,t=-7.099,P<0.001;B=-2.553,95%CI:-3.762~-1.345,t=-4.179,P<0.001).在人格因素中,外向性、神经质性及尽责性会影响患者的术后生活质量(B=0.469,95%CI:0.350~0.589,t=7.752,P<0.001;B=-0.654,95%CI:-0.823~-0.485,t=-7.671,P<0.001;B=0.545,95%CI:0.364~0.726,t=5.965,P<0.001).结论 乳腺癌改良根治术后女性患者焦虑、抑郁情绪的检出率高.人格因素可能对患者术后的情绪状态及生活质量有影响,临床医师可以根据患者不同的人格特点及术后心理状态选择不同的心理干预手段.
目的 探讨新辅助化疗对乳腺癌切除假体植入Ⅰ期乳房重建术后并发症及远期疗效的影响.方法 接受乳腺癌切除+假体植入Ⅰ期乳房重建手术的乳腺癌患者429例,其中术前接受2~8个周期新辅助化疗者236例为新辅助化疗组,直接行乳腺癌切除+假体植入Ⅰ期乳房重建术者193例为单纯手术组.比较2组手术方式、术后引流量、住院时间、术后并发症发生情况以及远期疗效.结果 新辅助化疗组101例采用腔镜辅助手术,135例行传统开放手术;单纯手术组75例采用腔镜辅助手术,118例行传统开放手术;2组手术方式比较差异无统计学意义(P>0.05).新辅助化疗组术后引流量[(284.0±79.4)mL]、术后住院时间[(5.6±1.2)d]与单纯手术组[(289.0±76.8)mL、(5.5±1.0)d]比较差异无统计学意义(P>0.05).2组术后血肿、手术区域感染、乳头乳晕及皮瓣坏死、患侧上肢水肿、包膜挛缩及假体丢失发生率比较差异均无统计学意义(P>0.05).新辅助化疗组局部复发率(2.12%)、远处转移发生率(7.63%)和病死率(3.39%)与单纯手术组(1.55%、5.70%、2.59%)比较差异均无统计学意义(P>0.05).结论 新辅助化疗对乳腺癌切除假体植入Ⅰ期乳房重建术后并发症及远期疗效无影响,在获得治疗效果的同时并未对乳房重建带来如伤口愈合不良或皮瓣坏死率增高等不利影响.
Objective To determine the clinicopathological features and prognostic differences between ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with microinvasion (DCIS-MI) of breast cancer. Methods A cohort of 489 female patients with surgically diagnosed DCIS (n=240, 49.1%) and DCIS-MI (n=249, 50.9%) in our hospital from January 2004 to December 2014 were recruited in this study. Their clinicopathological data and follow-up data were collected and analyzed for the differences in clinicopathological data, molecular subtypes and prognosis between DCIS and DCIS-MI patients. Results The age of initial diagnosis was usually younger than 55 years old (60.3%) in the 2 groups. Compared with DCIS patients, DCIS-MI patients had larger tumor size (P=0.034), higher histological grade (P < 0.05), and lower ER positive rate (P < 0.05); DCIS-MI patients had lower proportion of luminal-A type (54.6% vs 63.8%, P=0.040), while higher HER-2 over-expressed type (18.1% vs 9.2%, P=0.004). Statistical differences were seen in the distribution of molecular subtypes between the groups (Chi-square=8.921, P=0.030). The 5-year disease-free survival rate was 93.75% and 93.17% respectively in the DCIS and DCIS-MI patients, with no significant difference (Log-rank, Chi-square =0.074, P=0.785). Conclusion DCIS and DCIS-MI have different clinicopathological features and molecular subtype distribution, but no significant difference in prognosis, which indicates that they may be in different stages of breast cancer progression.
Triple negative breast cancer (TNBC) is a highly aggressive cancer and lack of targeting therapies.It is believed that the breast cancer stem cells (BCSCs) are responsible for the aggressive characteristics of TNBC.Hence, developing BCSC-targeting agents may provide new therapeutic strategies for the patients.Huaier polysaccharide (HP), an active ingredient extracted from the mushroom Trametes robiniophila Murr, has been widely used in clinical anti-cancer treatments in China.Here we demonstrated that HP could target BCSCs in TNBC cells, resulting in decreased mammosphere formation, downregulated expression of stem-related genes and reduced proportion of aldehyde dehydrogenase positive cells in vitro, and inhibited xenograft tumor formation in vivo.Mechanically, HP markedly reduced the expression of estrogen receptor α-36 (ERα-36), a recently identified subtype of estrogen receptor α, and attenuated ERα-36-mediated activation of AKT/β-catenin signaling in ERα-36 high TNBC cells.This study provides a new insight into the mechanism of HP on BCSC-targeting therapy and new ideas for comprehensive treatment strategies for TNBC.
目的 基因多态性与乳腺癌遗传易感性密切相关,但尚无神经外营养蛋白2(neurotrophin 2,NXPH2)基因与乳腺癌之间的报道.本研究探讨NXPH2基因rs4954956位点多态性与乳腺癌易感性的关联.方法 选取2012-01-01-2013-08-31就诊于陆军军医大学西南医院的新发女性乳腺癌病例709例,同一时期在门诊体检的健康女性749名作为对照,采用病例对照研究,提取研究对象外周血细胞基因组DNA,利用聚合酶链反应-连接酶反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)对rs4954956位点进行基因分型,多因素Logistic回归分析rs4954956位点多态性与乳腺癌易感性的关联.结果 709例乳腺癌病例中CC、CT、TT基因型分布分别为393(55.4%)、265(37.4%)和51(7.2%);749名对照中CC、CT、TT基因型分布分别为441(58.9%)、266(35.6%)和42(5.6%).统计分析显示,rs4954956位点与乳腺癌易感性均无统计学意义的关联(CT vs CC:OR=1.06,95%CI:0.85~1.33,P=0.59;TT vs CC:OR=1.31,95%CI:0.84~2.04,P=0.23;CT+TT vs CC:OR=1.10,95%CI:0.89~1.36,P=0.40;TT vs CC+CT:OR=1.28,95%CI:0.83~1.97,P=0.27;T vs C:OR=1.11,95%CI:0.93~1.31,P=0.26).在未绝经女性人群,共显性模型中隐性基因者(TT)相比于CC(校正OR=1.93,95%CI:1.07~3.48,P=0.03)、隐性模型中隐性基因者(TT)相比于CC+CT基因型者(校正OR=1.80,95%CI:1.01~3.22,P=0.048)、等位基因模型中T相比于C基因型者(校正OR=1.29,95%CI:1.04~1.60,P=0.02)患乳腺癌的风险均升高.结论 NXPH2基因rs4954956位点多态性与乳腺癌易感性无显著关联,但在未绝经女性人群中,隐性基因型(TT)较CC、CT基因型者患乳腺癌易感性升高.