Objective: Axillary lymph node dissection(ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node(NSLN) metastasis. The aim of the present study was to review the medical records of Chi...Objective: Axillary lymph node dissection(ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node(NSLN) metastasis. The aim of the present study was to review the medical records of Chinese patients with early-stage breast cancer and positive NSLN metastasis to identify clinicopathological characteristics as risk factors for non-NSLN metastasis.Methods: The medical records of 2008 early-stage breast cancer patients who received intraoperative sentinel lymph node biopsy(SLNB) between 2006 and 2016 were retrospectively reviewed. These patients were clinically and radiologically lymph nodenegative and had no prior history of receiving neoadjuvant chemotherapy or endocrinotherapy. The clinicopathological characteristics of patients with positive NSLN metastasis who underwent ALND were investigated.Results: In the present study, 296 patients with positive NSLN metastases underwent ALND. Positive non-NSLN metastases were confirmed in 95 patients(32.1%). On univariate analysis, ≥ 3 positive NSLN metastases(P <0.01), NSLN macrometastases(P =0.023), and lymphovascular invasion(P = 0.04) were associated with non-NSLN metastasis(P <0.05). In multivariate analysis, the number of positive SLNs was the most significant predictor of non-SLN metastasis. For patients with 0, 1, 2, or 3 associated risk factors, the non-SLN metastatic rates were 11.5%, 22.5%, 35.2%, and 73.1%, respectively.Conclusions: The number of positive NSLNs, NSLN macrometastases, and lymphovascular invasion were correlated with nonSLN metastasis. The number of positive SLNs was an independent predictor for non-NSLN metastasis. When 2 or 3 risk factors were present in one patient, the probability of non-NSLN was higher than that in the American College of Surgeons Oncology Group Z0011 trial(27.3%); thus, avoiding ALND should be considered carefully.展开更多
The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer(BC).This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages ...The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer(BC).This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC.We downloaded the GSE158399 dataset from the Gene Expression Omnibus(GEO)database,which includes transcriptomic profiles of individual cells from primary tumors,negative lymph nodes(NLNs),and positive lymph nodes(PLNs)of breast cancer patients.The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat.The activation and migration capability of M2 macrophages were evaluated with R package“GSVA”.The key M2 macrophages-related genes were screened from the differential expressed genes(DEGs)and M2 macrophages activation and migration gene sets collected from MSigDB database.Our analysis identified three main cell types in primary tumors,NLNs,and PLNs:basal cells,luminal cells,and immune cell subsets.The further cell type classification of immune cell subsets indicated M2 macrophages accumulation in NLs and PLs.The GSVA enrichment scores for activation and migration capability were increased significantly in M2 macrophages from primary tumors than NLNs and PLNs(pvalue<0.001).Seven M2 macrophages activation-related and 15 M2 macrophages migration-related genes were significantly up-regulated in primary tumors than NLNs and PLNs.The proportion and GSVA enrichment scores for activation and migration of M2 macrophages may be potential markers for lymph node metastasis in breast cancer.Our study demonstrated that twenty-two up-regulated mRNA may be possible therapeutic targets for lymph node metastasis in breast cancer.展开更多
AIM: To develop a method of delivering an eradicative high radiotherapeutic dose safely preserving the surrounding skin in the treatment of internal mammary lymph node metastasis (IMLNM) of breast cancer. METHODS: We ...AIM: To develop a method of delivering an eradicative high radiotherapeutic dose safely preserving the surrounding skin in the treatment of internal mammary lymph node metastasis (IMLNM) of breast cancer. METHODS: We report a 38-year-old female patient with a solo IMLNM showing no response to 60 Gy in 2.5 Gy fractions of external beam radiotherapy. To eradicate this tumor, a boost brachytherapy plan was created after percutaneous insertion of an applicator needle into the IMLNM lesion avoiding the pleura and vessels under ultrasound monitoring. According to the dose distribution, the required thickness of a spacer between the skin and the tumor was determined, and hyaluronic gel was injected up to this thickness under ultrasound monitoring. We evaluated skin doses, target doses and clinical outcome. RESULTS: All procedures were performed easily. Sixteen Gy (34.7 Gy equivalent in 2 Gy fractions calculated by the linear quadratic model at α/β = 10: EQD2, α/β = 10, cumulative total was 101.9 Gy EQD10) to 100% of the target volume was irradiated with cumulative maximum skin dose of 70 Gy EQD2, α/β = 3 which was 98.7 Gy EQD2, α/β = 3 without spacer. No procedure related- or late complications and no local recurrence at the treated site were observed for three years until expiration. CONCLUSION: We consider that this procedure will provide an eradicative high-dose irradiation to IMLNM of breast cancer, preserving skin from overdose complications.展开更多
Objective:To systematically evaluate the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis (SLNM) versus patients with stage Ⅲb/c or Ⅳ breast cancer,so as to provide evi...Objective:To systematically evaluate the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis (SLNM) versus patients with stage Ⅲb/c or Ⅳ breast cancer,so as to provide evidence for clinical practice and research.Methods:Computer retrieval from PubMed,Cochrane Libratory,CNKI (China National Knowledge Infrastructure),CBM and Wanfang Database with the assistance of other retrieval tools.All the studies evaluating the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis versus patients with stage Ⅲb/c or Ⅳ breast cancer were collected.Quality assessment was performed for the included data based on the quality assessment criteria appropriate for this study.Meta-analysis was performed using RevMan 5.3 software.Results:A total of four references (1277 patients) were included.Assessment of influences on prognosis:As compared to the stage Ⅲb/c group,the 5-year survival rate was slightly lower in the SLNM group (relative risk (RR) 0.79; 95% confidence interval (CI) 0.59-1.06; Z =1.55,P =0.12),but there was no statistical significance; in contrast,the 5-year survival rate was significantly increased in the SLNM group as compared to the stage Ⅳ group (RR =2.70; 95%CI:1.36-5.37; Z =2.84,P =0.005).As compared to the stage Ⅲb/c group,the 5-year disease-free survival rate was lower in the SLNM group (RR =0.65; 95%CI:0.40-1.05; Z =1.75,P =0.08); however,there was no statistical significance.Conclusions:In patients with advanced breast cancer receiving combined therapy,the prognosis in patients with breast cancer with ipsilateral SLNM was significantly better than in those with stage Ⅳ breast cancer,and slightly worse than those with stage Ⅲb/c breast cancer.However,with the scarcity and poor quality of these observational studies,the long-term prognosis remains to be further verified in large-sample,high-quality studies.展开更多
Background:Breast cancer patients with ipsilateral supraclavicular lymph node metastasis(ISLNM)but without distant metastasis are considered to have a poor prognosis.This study aimed to develop a nomogram to predict t...Background:Breast cancer patients with ipsilateral supraclavicular lymph node metastasis(ISLNM)but without distant metastasis are considered to have a poor prognosis.This study aimed to develop a nomogram to predict the overall survival(OS)of breast cancer patients with ISLNM but without distant metastasis.Methods:Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University,Jiyuan People’s Hospital and Huaxian People’s Hospital between December 21,2012 and June 30,2020 were reviewed retrospectively.Overall,345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified.They were further randomized 2:1 and divided into training(n=231)and validation(n=114)cohorts.A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses.The predictive accuracy and discriminative ability were measured by calibration plots,concordance index(C-index),and risk group stratification.Results:Univariable analysis showed that estrogen receptor-positive(ER+),progesterone receptor-positive(PR+),human epidermal growth factor receptor 2-positive(HER2+)with Herceptin treatment,and a low axillary lymph node ratio(ALNR)were prognostic factors for better OS.PR+,HER2+with Herceptin treatment,and a low ALNR remained independent prognostic factors for better OS on multivariable analysis.These variables were incorporated into a nomogram to predict the 1-,3-,and 5-year OS of breast cancer patients with ISLNM.The C-indexes of the nomogram were 0.737(95%confidence interval[CI]:0.660–0.813)and 0.759(95%CI:0.636–0.881)for the training and the validation cohorts,respectively.The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years,but not 1 year,OS in both the cohorts.The nomogram was also able to stratify patients into different risk groups.Conclusions:In this study,we established and validated a novel nomogram for predicting survival of patients with ISLNM.This nomogram may,to some extent,allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.展开更多
The aim of the study was to identify the relationship between molecular subtypes of breast cancer (BC) and the morphological characteristics of axillary lymph nodes (ALN) and metastatic risk in BC patients to clarify ...The aim of the study was to identify the relationship between molecular subtypes of breast cancer (BC) and the morphological characteristics of axillary lymph nodes (ALN) and metastatic risk in BC patients to clarify danger degree and justification of removal before metastases appear. Material and methods. Tumor molecular subtypes of 116 female BC patients aged 24 - 75 (53.9 ± 0.8) were determined by tumor tissue immunohistological examination (obtained by tru-cut biopsy), and the BC was classified as Luminal A, Luminal B/HER2−, Luminal B/HER2+, TNBC, and HER2+ subtypes. To interpret the results for the BC receptor status, immunohistochemical analysis was performed and interpreted according to the Allred scale. Lymph node size, shape, structure and conglomerates availability were recorded according to ultrasonography (USG) examination evaluated on “LOGIQ C5-Premium” (2012). Blood CA-15-3 levels were analyzed using a COBAS-e 411 automated analyzer. Statistical analysis of the obtained results was carried out using the SPSS-26 software package, and based on the t-Student-Bonferroni and H-Kruskal-Wallis criteria. The sensitivity and specificity of the indicators studied were determined using ROC statistical analysis. Results showed a significant association of some subtypes, as well as receptor expression, with tumor metastasis to ALN. Conclusion: 1) The HER2+ subtype is the most aggressive in terms of ALN metastasis. Although TNBC is the most aggressive subtype in general, it is characterized by fewer metastases to the ALN than the HER2+ subtype. 2) Metastatic ALNs can be distinguished based on their cortical structure before tumor tissue biopsy, which is economically profitable. These LNs can be removed without biopsy.展开更多
Background:Although sentinel lymph node biopsy(SLNB) can accurately predict the status of axillary lymph node(ALN) metastasis,the high false?negative rate(FNR) of SLNB is still the main obstacle for the treatment of p...Background:Although sentinel lymph node biopsy(SLNB) can accurately predict the status of axillary lymph node(ALN) metastasis,the high false?negative rate(FNR) of SLNB is still the main obstacle for the treatment of patients who receive SLNB instead of ALN dissection(ALND).The purpose of this study was to evaluate the clinical significance of SLNB combined with peripheral lymph node(PLN) sampling for reducing the FNR for breast cancer and to discuss the effect of "skip metastasis" on the FNR of SLNB.Methods:At Shandong Cancer Hospital Affiliated to Shandong University between March 1,2012 and June 30,2015,the sentinel lymph nodes(SLNs) of 596 patients with breast cancer were examined using radiocolloids with blue dye tracer.First,the SLNs were removed;then,the area surrounding the original SLNs was selected,and the visible lymph nodes in a field of 3–5 cm in diameter around the center(i.e.,PLNs) were removed,avoiding damage to the structure of the breast.Finally,ALND was performed.The SLNs,PLNs,and remaining ALNs underwent pathologic examination,and the relationship between them was analyzed.Results:The identification rate of SLNs in the 596 patients was 95.1%(567/596);the metastasis rate of ALNs was 33.7%(191/567);the FNR of pure SLNB was 9.9%(19/191);and after the SLNs and PLNs were eliminated,the FNR was 4.2%(8/191),which was significantly decreased compared with the FNR before removal of PLNs(P Aected number(N) of SLNs,the patients were divided into four groups of N = 0.028).ccording to the det= 1,2,3,and ≥4;the FNR in these groups was 19.6,9.8,7.3,and 2.3%,respectively.For the patients with removal of PLNs was significantly decreased compared with that before remo≤2 or val of P≤3 detected SLNs,the FNR afterLNs(N 3:12.2% vs.4.7%,P ≤ 2:14.0% vs.4.7%,P = 0.019;N ≤ nt(P = 0.021),whereas for patients with ≥4 detected SLNs,the decrease in FNR was not statistically significa= 1.000).In the entire cohorts,the "skip metastasis" rate was 2.5%(15/596);the FNR caused by "skip metastasis" was 2.1%(4/191).Conclusions:The FNR of SLNB was associated with the number of SLNs.For patients with mpling can reduce the FNR of SLNB to an acceptable level of less than 5%.Because of the≤3 detected SLNs,PLN sa existence of the "skip metastasis" and distinct metastasis patterns,the FNR of SLNB cannot be completely eliminated.展开更多
Objective: To study angiogenesis of the axillary lymph node metastases including micrometastases in breast carcinoma and the relationship between microvessel density (MVD) and metastasis. Methods: Thirty-seven breast...Objective: To study angiogenesis of the axillary lymph node metastases including micrometastases in breast carcinoma and the relationship between microvessel density (MVD) and metastasis. Methods: Thirty-seven breast cancer tissues and 121 metastatic axillary lymph nodes were collected from the patients and studied immuno-histochemically. MVD was counted by means of microvideo system under 100 magnification. The diameter of each micrometastasis was measured with a micrometer. Results: The mean diameter of 13 micrometastatic foci was 210±37 mm. No blood vessel formation was found. MVD of the primary tumor and that of metastatic tumor in the axillary lymph node were 93.8±21.8 and 89.3±18.4, respectively (P<0.05). The distribution of microvessels of the metastatic tumor in the lymph node and that of the primary tumor was similar, being higher at the periphery than at the center. Conclusion: Micrometastatic foci of breast carcinoma in the axillary lymph node do not have new blood vessel formation. Their further growth, however, depends on neo-angiogenesis. Treatment based on inhibition of angiogenesis may be efficacious in the prevention of micrometastatic foci from developing into metastatic tumor in lymph node.展开更多
Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymp...Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.展开更多
Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary...Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.展开更多
Lymph node involvement increases the risk of breast cancer recurrence.An accurate non-invasive assessment of nodal involvement is valuable in cancer staging,surgical risk,and cost savings.Radiomics has been proposed t...Lymph node involvement increases the risk of breast cancer recurrence.An accurate non-invasive assessment of nodal involvement is valuable in cancer staging,surgical risk,and cost savings.Radiomics has been proposed to pre-operatively predict sentinel lymph node(SLN)status;however,radiomic models are known to be sensitive to acquisition parameters.The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based(DLB)features and compare its predictive performance to state-of-the-art radiomics.Specifically,this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution.Dynamic contrast-enhancement images from 198 patients(67 positive SLNs)were used in this study.Of these subjects,163 had an in-plane resolution of 0.7×0.7 mm^(2),which were randomly divided into a training set(approximately 67%)and a validation set(approximately 33%).The remaining 35 subjects with a different in-plane resolution(0.78×0.78 mm^(2))were treated as independent testing set for generalizability.Two methods were employed:(1)conventional radiomics(CR),and(2)DLB features which replaced hand-curated features with pre-trained VGG-16 features.The threshold determined using the training set was applied to the independent validation and testing dataset.Same feature reduction,feature selection,model creation procedures were used for both approaches.In the validation set(same resolution as training),the DLB model outperformed the CR model(accuracy 83%vs 80%).Furthermore,in the independent testing set of the dissimilar resolution,the DLB model performed markedly better than the CR model(accuracy 77%vs 71%).The predictive performance of the DLB model outperformed the CR model for this task.More interestingly,these improvements were seen particularly in the independent testing set of dissimilar resolution.This could indicate that DLB features can ultimately result in a more generalizable model.展开更多
BACKGROUND With sentinel node metastasis in breast cancer(BC)patients,axillary lymph node(ALN)dissection is often omitted from cases with breast-conserving surgery.Omission of lymph node dissection reduces the invasiv...BACKGROUND With sentinel node metastasis in breast cancer(BC)patients,axillary lymph node(ALN)dissection is often omitted from cases with breast-conserving surgery.Omission of lymph node dissection reduces the invasiveness of surgery to the patient,but it also obscures the number of metastases to non-sentinel nodes.The possibility of finding≥4 lymph nodes(pN2a/pN3a)preoperatively is important given the ramifications for postoperative treatment.AIM To search for clinicopathological factors that predicts upstaging from N0 to pN2a/pN3a.METHODS Patients who were sentinel lymph node(SLN)-positive and underwent ALN dissection between September 2007 and August 2018 were selected by retrospective chart review.All patients had BC diagnosed preoperatively as N0 with axillary evaluation by fluorodeoxyglucose(FDG) positron emission tomography/computed tomography and ultrasound (US)examination. When suspicious FDG accumulation was found in ALN, the presence of metastasiswas reevaluated by second US. We examined predictors of upstaging from N0 to pN2a/pN3a.RESULTSAmong 135 patients, we identified 1-3 ALNs (pN1) in 113 patients and ³4 ALNs (pN2a/pN3a) in22 patients. Multivariate analysis identified the total number of SLN metastasis, the maximaldiameter of metastasis in the SLN (SLNDmax), and FDG accumulation of ALN as predictors ofupstaging to pN2a/pN3a.CONCLUSIONWe identified factors involved in upstaging from N0 to pN2a/pN3a. The SLNDmax and numberof SLN metastasis are predictors of ≥ 4 ALNs (pN2a/pN3a) and predictors of metastasis to nonsentinelnodes, which have been reported in the past. Attention should be given to axillaryaccumulations of FDG, even when faint.展开更多
Ductal breast cancer is a clinically heterogeneous disease;we investigate the correlation between tumor size, comedo necrosis, number of cell mitoses and axillary lymph node metastasis in ductal breast cancer. In this...Ductal breast cancer is a clinically heterogeneous disease;we investigate the correlation between tumor size, comedo necrosis, number of cell mitoses and axillary lymph node metastasis in ductal breast cancer. In this study, 104 ductal breast cancer specimens were collected and divided into 3 groups: T1 group (tumor size ≤ 2 cm), T2 group (2 5.0 cm). Among those specimens, 95 cases were diagnosed with invasive ducted carcinoma, and 9 cases were ductal carcinoma in-situ (DCIS). Results show that T3 group has a higher rate of axillary lymph node metastasis than T2 group and T1 group;T2 group has a higher rate of lymph node metastasis than T1 group. The patients with the number of cell mitoses (≥10) were also has a higher rate of axillary lymph node metastasis (P = 0.0139) than the patients with the number of cell mitoses (<10). No significance was found between comedo necrosis lesions and axillary lymph node metastasis, though the frequency of comedo necrosis lesions in patients with axillary lymph node metastasis was higher than those in non-metastatic patients. It is concluded that the tumor size and the number of cell mitoses were risk factors for axillary lymph node involvement in ductal breast cancer.展开更多
The presence or absence of metastases in the axillary lymph nodes has remained the most powerful prognostic factor in breast carcinoma. Axillary lymph node dissection (ALND) is the standard procedure for obtaining t...The presence or absence of metastases in the axillary lymph nodes has remained the most powerful prognostic factor in breast carcinoma. Axillary lymph node dissection (ALND) is the standard procedure for obtaining this information. However, postoperative complications are common. Sentinel lymph node (SLN) biopsy has been proposed as a potential alternative to ALND for staging breast carcinoma. This technique has been shown to be sensitive and specific for predicting the status of the axillary lymph nodes. Furthermore, it has the potential advantage of decreasing the morbidity associated with ALND.展开更多
Breast cancer is one of the most common malignant tumors in women all over the world.Metastasis represents a major adverse progression of breast cancer,resulting in poor survival duration.Axillary lymph node metastasi...Breast cancer is one of the most common malignant tumors in women all over the world.Metastasis represents a major adverse progression of breast cancer,resulting in poor survival duration.Axillary lymph node metastasis is often the first step of systemic metastasis process of breast cancer.However,themechanismof lymph node metastasis and the genomic signatures of primary breast tumors and lymph node metastasis are still under exploration.Whole exome sequencing was applied to primary breast cancer,axillary metastatic lymph nodes,andwhite blood cells from10Chinesewomen patients in our study.Single nucleotide variants(SNVs)and copynumber variants(CNVs)were compared between primary tumors and lymph nodes for individual patients.There are somatic SNVs(average 5.58±2.56 per megabase)in primary breast cancers and somatic SNVs(average 5.46±2.66 per megabase)in axillary metastatic lymph nodes were identified,which is corresponding to a semblable mutation burden in two malignant sites(P=0.81).No difference was found in CNVs(P=0.33).In primary breast cancer,somatic SNVs(48.12±13.80%)and CNVs(61.72±35.00%)were overlapping with somatic SNVs(49.43±12.30%)and CNVs(72.01±24.31%)in axillary metastatic lymph nodes.Nine genes were screened for significant specificmutations in primary tumors,and 15 genes were significantly mutated in metastatic lymph nodes.Using MutSigCV screening,it was found that HRNR and AHNAK2 are lymph node metastasis-specific genes.In our study,primary breast tumors are directly related to axillary lymph node metastases together and there are most SNVs and CNVs which were overlapping in primary andmetastatic sites.These variants which are overlapping is closely related to themetastatic process of tumor invasion with early genetic variability.This is the first timeto prove the concept of polyclonalmetastaticmodel and in thismodelmore than one clonemigrates establish the metastases to axillary lymph nodes.This study was approved by the institutional review board(IRB)of the Cancer Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College,China(approval No.NCC2016G-030)on March 3,2016.展开更多
Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features As most breast can...Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features As most breast cancers are sex hormone-dependent, adipocytokines derived from adipose tissue, such as leptin, may account for the positive association between obesity and breast cancer. Leptin, a 16-kDa protein product of the obese gene, was initially regarded as a neuroendocrine factor in the hypothalamus to maintain homeostasis of body weight by regulating food intake and energy expenditure.展开更多
文摘Objective: Axillary lymph node dissection(ALND) may be unnecessary in 20%–60% of breast cancer patients with sentinel lymph node(NSLN) metastasis. The aim of the present study was to review the medical records of Chinese patients with early-stage breast cancer and positive NSLN metastasis to identify clinicopathological characteristics as risk factors for non-NSLN metastasis.Methods: The medical records of 2008 early-stage breast cancer patients who received intraoperative sentinel lymph node biopsy(SLNB) between 2006 and 2016 were retrospectively reviewed. These patients were clinically and radiologically lymph nodenegative and had no prior history of receiving neoadjuvant chemotherapy or endocrinotherapy. The clinicopathological characteristics of patients with positive NSLN metastasis who underwent ALND were investigated.Results: In the present study, 296 patients with positive NSLN metastases underwent ALND. Positive non-NSLN metastases were confirmed in 95 patients(32.1%). On univariate analysis, ≥ 3 positive NSLN metastases(P <0.01), NSLN macrometastases(P =0.023), and lymphovascular invasion(P = 0.04) were associated with non-NSLN metastasis(P <0.05). In multivariate analysis, the number of positive SLNs was the most significant predictor of non-SLN metastasis. For patients with 0, 1, 2, or 3 associated risk factors, the non-SLN metastatic rates were 11.5%, 22.5%, 35.2%, and 73.1%, respectively.Conclusions: The number of positive NSLNs, NSLN macrometastases, and lymphovascular invasion were correlated with nonSLN metastasis. The number of positive SLNs was an independent predictor for non-NSLN metastasis. When 2 or 3 risk factors were present in one patient, the probability of non-NSLN was higher than that in the American College of Surgeons Oncology Group Z0011 trial(27.3%); thus, avoiding ALND should be considered carefully.
文摘The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer(BC).This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC.We downloaded the GSE158399 dataset from the Gene Expression Omnibus(GEO)database,which includes transcriptomic profiles of individual cells from primary tumors,negative lymph nodes(NLNs),and positive lymph nodes(PLNs)of breast cancer patients.The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat.The activation and migration capability of M2 macrophages were evaluated with R package“GSVA”.The key M2 macrophages-related genes were screened from the differential expressed genes(DEGs)and M2 macrophages activation and migration gene sets collected from MSigDB database.Our analysis identified three main cell types in primary tumors,NLNs,and PLNs:basal cells,luminal cells,and immune cell subsets.The further cell type classification of immune cell subsets indicated M2 macrophages accumulation in NLs and PLs.The GSVA enrichment scores for activation and migration capability were increased significantly in M2 macrophages from primary tumors than NLNs and PLNs(pvalue<0.001).Seven M2 macrophages activation-related and 15 M2 macrophages migration-related genes were significantly up-regulated in primary tumors than NLNs and PLNs.The proportion and GSVA enrichment scores for activation and migration of M2 macrophages may be potential markers for lymph node metastasis in breast cancer.Our study demonstrated that twenty-two up-regulated mRNA may be possible therapeutic targets for lymph node metastasis in breast cancer.
基金Supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology,Japan (MEXT), grant number 23659595 (in part)
文摘AIM: To develop a method of delivering an eradicative high radiotherapeutic dose safely preserving the surrounding skin in the treatment of internal mammary lymph node metastasis (IMLNM) of breast cancer. METHODS: We report a 38-year-old female patient with a solo IMLNM showing no response to 60 Gy in 2.5 Gy fractions of external beam radiotherapy. To eradicate this tumor, a boost brachytherapy plan was created after percutaneous insertion of an applicator needle into the IMLNM lesion avoiding the pleura and vessels under ultrasound monitoring. According to the dose distribution, the required thickness of a spacer between the skin and the tumor was determined, and hyaluronic gel was injected up to this thickness under ultrasound monitoring. We evaluated skin doses, target doses and clinical outcome. RESULTS: All procedures were performed easily. Sixteen Gy (34.7 Gy equivalent in 2 Gy fractions calculated by the linear quadratic model at α/β = 10: EQD2, α/β = 10, cumulative total was 101.9 Gy EQD10) to 100% of the target volume was irradiated with cumulative maximum skin dose of 70 Gy EQD2, α/β = 3 which was 98.7 Gy EQD2, α/β = 3 without spacer. No procedure related- or late complications and no local recurrence at the treated site were observed for three years until expiration. CONCLUSION: We consider that this procedure will provide an eradicative high-dose irradiation to IMLNM of breast cancer, preserving skin from overdose complications.
基金This study was supported by the grants from the National Natural Science Foundation of China,the Science and Technology Agency of Liaoning Province
文摘Objective:To systematically evaluate the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis (SLNM) versus patients with stage Ⅲb/c or Ⅳ breast cancer,so as to provide evidence for clinical practice and research.Methods:Computer retrieval from PubMed,Cochrane Libratory,CNKI (China National Knowledge Infrastructure),CBM and Wanfang Database with the assistance of other retrieval tools.All the studies evaluating the prognosis in patients with breast cancer with ipsilateral supraclavicular lymph node metastasis versus patients with stage Ⅲb/c or Ⅳ breast cancer were collected.Quality assessment was performed for the included data based on the quality assessment criteria appropriate for this study.Meta-analysis was performed using RevMan 5.3 software.Results:A total of four references (1277 patients) were included.Assessment of influences on prognosis:As compared to the stage Ⅲb/c group,the 5-year survival rate was slightly lower in the SLNM group (relative risk (RR) 0.79; 95% confidence interval (CI) 0.59-1.06; Z =1.55,P =0.12),but there was no statistical significance; in contrast,the 5-year survival rate was significantly increased in the SLNM group as compared to the stage Ⅳ group (RR =2.70; 95%CI:1.36-5.37; Z =2.84,P =0.005).As compared to the stage Ⅲb/c group,the 5-year disease-free survival rate was lower in the SLNM group (RR =0.65; 95%CI:0.40-1.05; Z =1.75,P =0.08); however,there was no statistical significance.Conclusions:In patients with advanced breast cancer receiving combined therapy,the prognosis in patients with breast cancer with ipsilateral SLNM was significantly better than in those with stage Ⅳ breast cancer,and slightly worse than those with stage Ⅲb/c breast cancer.However,with the scarcity and poor quality of these observational studies,the long-term prognosis remains to be further verified in large-sample,high-quality studies.
基金the Science and Technology development plan of He’nan(No.202102310428).
文摘Background:Breast cancer patients with ipsilateral supraclavicular lymph node metastasis(ISLNM)but without distant metastasis are considered to have a poor prognosis.This study aimed to develop a nomogram to predict the overall survival(OS)of breast cancer patients with ISLNM but without distant metastasis.Methods:Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University,Jiyuan People’s Hospital and Huaxian People’s Hospital between December 21,2012 and June 30,2020 were reviewed retrospectively.Overall,345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified.They were further randomized 2:1 and divided into training(n=231)and validation(n=114)cohorts.A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses.The predictive accuracy and discriminative ability were measured by calibration plots,concordance index(C-index),and risk group stratification.Results:Univariable analysis showed that estrogen receptor-positive(ER+),progesterone receptor-positive(PR+),human epidermal growth factor receptor 2-positive(HER2+)with Herceptin treatment,and a low axillary lymph node ratio(ALNR)were prognostic factors for better OS.PR+,HER2+with Herceptin treatment,and a low ALNR remained independent prognostic factors for better OS on multivariable analysis.These variables were incorporated into a nomogram to predict the 1-,3-,and 5-year OS of breast cancer patients with ISLNM.The C-indexes of the nomogram were 0.737(95%confidence interval[CI]:0.660–0.813)and 0.759(95%CI:0.636–0.881)for the training and the validation cohorts,respectively.The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years,but not 1 year,OS in both the cohorts.The nomogram was also able to stratify patients into different risk groups.Conclusions:In this study,we established and validated a novel nomogram for predicting survival of patients with ISLNM.This nomogram may,to some extent,allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.
文摘The aim of the study was to identify the relationship between molecular subtypes of breast cancer (BC) and the morphological characteristics of axillary lymph nodes (ALN) and metastatic risk in BC patients to clarify danger degree and justification of removal before metastases appear. Material and methods. Tumor molecular subtypes of 116 female BC patients aged 24 - 75 (53.9 ± 0.8) were determined by tumor tissue immunohistological examination (obtained by tru-cut biopsy), and the BC was classified as Luminal A, Luminal B/HER2−, Luminal B/HER2+, TNBC, and HER2+ subtypes. To interpret the results for the BC receptor status, immunohistochemical analysis was performed and interpreted according to the Allred scale. Lymph node size, shape, structure and conglomerates availability were recorded according to ultrasonography (USG) examination evaluated on “LOGIQ C5-Premium” (2012). Blood CA-15-3 levels were analyzed using a COBAS-e 411 automated analyzer. Statistical analysis of the obtained results was carried out using the SPSS-26 software package, and based on the t-Student-Bonferroni and H-Kruskal-Wallis criteria. The sensitivity and specificity of the indicators studied were determined using ROC statistical analysis. Results showed a significant association of some subtypes, as well as receptor expression, with tumor metastasis to ALN. Conclusion: 1) The HER2+ subtype is the most aggressive in terms of ALN metastasis. Although TNBC is the most aggressive subtype in general, it is characterized by fewer metastases to the ALN than the HER2+ subtype. 2) Metastatic ALNs can be distinguished based on their cortical structure before tumor tissue biopsy, which is economically profitable. These LNs can be removed without biopsy.
文摘Background:Although sentinel lymph node biopsy(SLNB) can accurately predict the status of axillary lymph node(ALN) metastasis,the high false?negative rate(FNR) of SLNB is still the main obstacle for the treatment of patients who receive SLNB instead of ALN dissection(ALND).The purpose of this study was to evaluate the clinical significance of SLNB combined with peripheral lymph node(PLN) sampling for reducing the FNR for breast cancer and to discuss the effect of "skip metastasis" on the FNR of SLNB.Methods:At Shandong Cancer Hospital Affiliated to Shandong University between March 1,2012 and June 30,2015,the sentinel lymph nodes(SLNs) of 596 patients with breast cancer were examined using radiocolloids with blue dye tracer.First,the SLNs were removed;then,the area surrounding the original SLNs was selected,and the visible lymph nodes in a field of 3–5 cm in diameter around the center(i.e.,PLNs) were removed,avoiding damage to the structure of the breast.Finally,ALND was performed.The SLNs,PLNs,and remaining ALNs underwent pathologic examination,and the relationship between them was analyzed.Results:The identification rate of SLNs in the 596 patients was 95.1%(567/596);the metastasis rate of ALNs was 33.7%(191/567);the FNR of pure SLNB was 9.9%(19/191);and after the SLNs and PLNs were eliminated,the FNR was 4.2%(8/191),which was significantly decreased compared with the FNR before removal of PLNs(P Aected number(N) of SLNs,the patients were divided into four groups of N = 0.028).ccording to the det= 1,2,3,and ≥4;the FNR in these groups was 19.6,9.8,7.3,and 2.3%,respectively.For the patients with removal of PLNs was significantly decreased compared with that before remo≤2 or val of P≤3 detected SLNs,the FNR afterLNs(N 3:12.2% vs.4.7%,P ≤ 2:14.0% vs.4.7%,P = 0.019;N ≤ nt(P = 0.021),whereas for patients with ≥4 detected SLNs,the decrease in FNR was not statistically significa= 1.000).In the entire cohorts,the "skip metastasis" rate was 2.5%(15/596);the FNR caused by "skip metastasis" was 2.1%(4/191).Conclusions:The FNR of SLNB was associated with the number of SLNs.For patients with mpling can reduce the FNR of SLNB to an acceptable level of less than 5%.Because of the≤3 detected SLNs,PLN sa existence of the "skip metastasis" and distinct metastasis patterns,the FNR of SLNB cannot be completely eliminated.
基金a grant from Shandong Science and Technology Commission! (No. 961226702)
文摘Objective: To study angiogenesis of the axillary lymph node metastases including micrometastases in breast carcinoma and the relationship between microvessel density (MVD) and metastasis. Methods: Thirty-seven breast cancer tissues and 121 metastatic axillary lymph nodes were collected from the patients and studied immuno-histochemically. MVD was counted by means of microvideo system under 100 magnification. The diameter of each micrometastasis was measured with a micrometer. Results: The mean diameter of 13 micrometastatic foci was 210±37 mm. No blood vessel formation was found. MVD of the primary tumor and that of metastatic tumor in the axillary lymph node were 93.8±21.8 and 89.3±18.4, respectively (P<0.05). The distribution of microvessels of the metastatic tumor in the lymph node and that of the primary tumor was similar, being higher at the periphery than at the center. Conclusion: Micrometastatic foci of breast carcinoma in the axillary lymph node do not have new blood vessel formation. Their further growth, however, depends on neo-angiogenesis. Treatment based on inhibition of angiogenesis may be efficacious in the prevention of micrometastatic foci from developing into metastatic tumor in lymph node.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant Nos.2016ZX310182-2 and 2016ZX310176-6 to NY)the Medical Epigenetics Research Center,Chinese Academy of Medical Sciences(Grant Nos.2017PT31035 and 2018PT31035 to NY)the National Natural Science Foundation of China(Grant No.81773163 to JF)
文摘Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.
文摘Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary tumor.By definition,no residual lymph node structure should be identified in these tumor masses.At present,TDs are mainly reported in colorectal cancer,with a few reports in gastric cancer.There are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor tissue.Even some pathologists classify a TD as two lymph node metastases for calculation.Some pathologists also believe that TDs belong to the category of disseminated metastasis.Therefore,regardless of the origin,TDs are an indicator of poor prognosis.Moreover,for BC,sentinel lymph node biopsy is generally used at present.Whether radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still inconclusive.The present commentary of this clinical issue has certain guiding significance.It is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.
基金This work was supported in part by National Cancer Institute,No.R03CA223052Walk-for-Beauty Foundation and Baldwin Carol M.Baldwin Breast Cancer Research Awards。
文摘Lymph node involvement increases the risk of breast cancer recurrence.An accurate non-invasive assessment of nodal involvement is valuable in cancer staging,surgical risk,and cost savings.Radiomics has been proposed to pre-operatively predict sentinel lymph node(SLN)status;however,radiomic models are known to be sensitive to acquisition parameters.The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based(DLB)features and compare its predictive performance to state-of-the-art radiomics.Specifically,this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution.Dynamic contrast-enhancement images from 198 patients(67 positive SLNs)were used in this study.Of these subjects,163 had an in-plane resolution of 0.7×0.7 mm^(2),which were randomly divided into a training set(approximately 67%)and a validation set(approximately 33%).The remaining 35 subjects with a different in-plane resolution(0.78×0.78 mm^(2))were treated as independent testing set for generalizability.Two methods were employed:(1)conventional radiomics(CR),and(2)DLB features which replaced hand-curated features with pre-trained VGG-16 features.The threshold determined using the training set was applied to the independent validation and testing dataset.Same feature reduction,feature selection,model creation procedures were used for both approaches.In the validation set(same resolution as training),the DLB model outperformed the CR model(accuracy 83%vs 80%).Furthermore,in the independent testing set of the dissimilar resolution,the DLB model performed markedly better than the CR model(accuracy 77%vs 71%).The predictive performance of the DLB model outperformed the CR model for this task.More interestingly,these improvements were seen particularly in the independent testing set of dissimilar resolution.This could indicate that DLB features can ultimately result in a more generalizable model.
文摘BACKGROUND With sentinel node metastasis in breast cancer(BC)patients,axillary lymph node(ALN)dissection is often omitted from cases with breast-conserving surgery.Omission of lymph node dissection reduces the invasiveness of surgery to the patient,but it also obscures the number of metastases to non-sentinel nodes.The possibility of finding≥4 lymph nodes(pN2a/pN3a)preoperatively is important given the ramifications for postoperative treatment.AIM To search for clinicopathological factors that predicts upstaging from N0 to pN2a/pN3a.METHODS Patients who were sentinel lymph node(SLN)-positive and underwent ALN dissection between September 2007 and August 2018 were selected by retrospective chart review.All patients had BC diagnosed preoperatively as N0 with axillary evaluation by fluorodeoxyglucose(FDG) positron emission tomography/computed tomography and ultrasound (US)examination. When suspicious FDG accumulation was found in ALN, the presence of metastasiswas reevaluated by second US. We examined predictors of upstaging from N0 to pN2a/pN3a.RESULTSAmong 135 patients, we identified 1-3 ALNs (pN1) in 113 patients and ³4 ALNs (pN2a/pN3a) in22 patients. Multivariate analysis identified the total number of SLN metastasis, the maximaldiameter of metastasis in the SLN (SLNDmax), and FDG accumulation of ALN as predictors ofupstaging to pN2a/pN3a.CONCLUSIONWe identified factors involved in upstaging from N0 to pN2a/pN3a. The SLNDmax and numberof SLN metastasis are predictors of ≥ 4 ALNs (pN2a/pN3a) and predictors of metastasis to nonsentinelnodes, which have been reported in the past. Attention should be given to axillaryaccumulations of FDG, even when faint.
文摘Ductal breast cancer is a clinically heterogeneous disease;we investigate the correlation between tumor size, comedo necrosis, number of cell mitoses and axillary lymph node metastasis in ductal breast cancer. In this study, 104 ductal breast cancer specimens were collected and divided into 3 groups: T1 group (tumor size ≤ 2 cm), T2 group (2 5.0 cm). Among those specimens, 95 cases were diagnosed with invasive ducted carcinoma, and 9 cases were ductal carcinoma in-situ (DCIS). Results show that T3 group has a higher rate of axillary lymph node metastasis than T2 group and T1 group;T2 group has a higher rate of lymph node metastasis than T1 group. The patients with the number of cell mitoses (≥10) were also has a higher rate of axillary lymph node metastasis (P = 0.0139) than the patients with the number of cell mitoses (<10). No significance was found between comedo necrosis lesions and axillary lymph node metastasis, though the frequency of comedo necrosis lesions in patients with axillary lymph node metastasis was higher than those in non-metastatic patients. It is concluded that the tumor size and the number of cell mitoses were risk factors for axillary lymph node involvement in ductal breast cancer.
文摘The presence or absence of metastases in the axillary lymph nodes has remained the most powerful prognostic factor in breast carcinoma. Axillary lymph node dissection (ALND) is the standard procedure for obtaining this information. However, postoperative complications are common. Sentinel lymph node (SLN) biopsy has been proposed as a potential alternative to ALND for staging breast carcinoma. This technique has been shown to be sensitive and specific for predicting the status of the axillary lymph nodes. Furthermore, it has the potential advantage of decreasing the morbidity associated with ALND.
基金This research was funded in part by the National Natural Science Foundation of China(81602343 to Xin Wang)the Chinese Academy of Medical Sciences(CAMS)initiative Fund for Medical Sciences,China(2016-I2M-1-001 to Xiang Wang,2017-I2M-3-004 to Xin Wang)+3 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,China(2018PT32013,2017PT32001 and 2016ZX310178 to Xin Wang)the Beijing Hope Run Special Fund,China(LC2017B15 to Xin Wang)the Capital’s Funds for Health Improvement and Research,China(2016-4-4026 to Xin Wang)Youth Research Fund of Beijing Tiantan Hospital,China(2017-YQN-09 to Wenyan Wang).
文摘Breast cancer is one of the most common malignant tumors in women all over the world.Metastasis represents a major adverse progression of breast cancer,resulting in poor survival duration.Axillary lymph node metastasis is often the first step of systemic metastasis process of breast cancer.However,themechanismof lymph node metastasis and the genomic signatures of primary breast tumors and lymph node metastasis are still under exploration.Whole exome sequencing was applied to primary breast cancer,axillary metastatic lymph nodes,andwhite blood cells from10Chinesewomen patients in our study.Single nucleotide variants(SNVs)and copynumber variants(CNVs)were compared between primary tumors and lymph nodes for individual patients.There are somatic SNVs(average 5.58±2.56 per megabase)in primary breast cancers and somatic SNVs(average 5.46±2.66 per megabase)in axillary metastatic lymph nodes were identified,which is corresponding to a semblable mutation burden in two malignant sites(P=0.81).No difference was found in CNVs(P=0.33).In primary breast cancer,somatic SNVs(48.12±13.80%)and CNVs(61.72±35.00%)were overlapping with somatic SNVs(49.43±12.30%)and CNVs(72.01±24.31%)in axillary metastatic lymph nodes.Nine genes were screened for significant specificmutations in primary tumors,and 15 genes were significantly mutated in metastatic lymph nodes.Using MutSigCV screening,it was found that HRNR and AHNAK2 are lymph node metastasis-specific genes.In our study,primary breast tumors are directly related to axillary lymph node metastases together and there are most SNVs and CNVs which were overlapping in primary andmetastatic sites.These variants which are overlapping is closely related to themetastatic process of tumor invasion with early genetic variability.This is the first timeto prove the concept of polyclonalmetastaticmodel and in thismodelmore than one clonemigrates establish the metastases to axillary lymph nodes.This study was approved by the institutional review board(IRB)of the Cancer Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College,China(approval No.NCC2016G-030)on March 3,2016.
基金This work was supported by the grants from Capital Foundation for Development of Medical Science (No. 2005-2031) and National Natural Science Foundation of China (No. 30772121).
文摘Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features As most breast cancers are sex hormone-dependent, adipocytokines derived from adipose tissue, such as leptin, may account for the positive association between obesity and breast cancer. Leptin, a 16-kDa protein product of the obese gene, was initially regarded as a neuroendocrine factor in the hypothalamus to maintain homeostasis of body weight by regulating food intake and energy expenditure.