Objective: To investigate the characteristics of clinical manifestations, diagnosis and treatment of NEBC (neuroendocrine breast cancer). Methods: This was a retrospective study. Ten consecutive female patients with NEBC were admitted in Department of Breast Surgery, Peking Union Medical College Hospital between January 2004 and December 2010. The average age of the ten patients was 52 years, and the follow-up period was 24-177 months (median 84 months). Results: Clinically, most of the NEBC manifested as breast lump, sometimes as NPBL (non-palpable breast lesion) or nipple discharge. An ultrasound examination usually revealed heterogeneous echoic mass with irregular shape and clear boundary. Mammography showed no significantly different changes from other kinds of breast cancer. Nine patients received curative resection for NEBC, among whom, seven underwent modified radical mastectomy, one underwent nipple and areola-sparing modified radical mastectomy, one with nipple discharge underwent excision of duct and relevant lobule and hook-wire-guided biopsy of breast lump, and later right mastectomy with sentinel lymph node biopsy. The expressions of hormone receptors like ER (estrogen receptor) /PR (progesterone receptor) were usually positive in NEBC, while the expression of HER2 (human epidermal growth factor receptor 2) was usually negative (–) to positive (+). At least one neuroendocrine marker like Syn (synapsin) or CgA (chromgranin A) was positive. During the follow-up period, metastasis was found in two patients and one of them had passed away. Conclusion: NEBC is a clinical entity different from breast cancer with BC-NE (breast cancer with neuroendocrine differentiation). NEBC may affect younger patients in China, ultrasound examination is valuable for diagnosis, and surgical and comprehensive therapy may achieve satisfactory outcome with relatively good prognosis, although there might be cases of metastasis. DOI:10.3781/j.issn.1000-7431.2013.02.011
Abstract Drug and xenobiotic metabolizing enzymes (DXME) play important roles in drug responses and carcinogenesis. Recent studies have found that expression of DXME in cancer cells significantly affects drug clearance and the onset of drug resistance. In this study we compared the expression of DXME in breast tumor tissue samples from patients representing three ethnic groups: Caucasian Americans (CA), African Americans (AA), and Asian Americans (AS). We further combined DXME gene expression data with eQTL data from the GTEx project and with allele frequency data from the 1000 Genomes project to identify SNPs that may be associated with differential expression of DXME genes. We identified substantial differences among CA, AA, and AS populations in the expression of DXME genes and in activation of pathways involved in drug metabolism, including those involved in metabolizing chemotherapy drugs that are commonly used in the treatment of breast cancer. These data suggest that differential expression of DXME may associate with health disparities in breast cancer outcomes observed among these three ethnic groups. Our study suggests that development of personalized treatment strategies for breast cancer patients could be improved by considering both germline genotypes and tumor specific mutations and expression profiles related to DXME genes.
Objectives The contribution of ultrasound-assisted thoracic paravertebral block to postoperative analgesia remains unclear. We compared the effect of a combination of ultrasound assisted-thoracic paravertebral block and propofol general anesthesia with opioid and sevoflurane general anesthesia on volatile anesthetic, propofol and opioid consumption, and postoperative pain in patients having breast cancer surgery. Methods Patients undergoing breast cancer surgery were randomly assigned to ultrasound-assisted paravertebral block with propofol general anesthesia (PPA group, n = 121) or fentanyl with sevoflurane general anesthesia (GA group, n = 126). Volatile anesthetic, propofol and opioid consumption, and postoperative pain intensity were compared between the groups using noninferiority and superiority tests. Results Patients in the PPA group required less sevoflurane than those in the GA group (median [interquartile range] of 0 [0, 0] vs. 0.4 [0.3, 0.6] minimum alveolar concentration [MAC]-hours), less intraoperative fentanyl requirements (100 [50, 100] vs. 250 [200, 300]μg,), less intense postoperative pain (median visual analog scale score 2 [1, 3.5] vs. 3 [2, 4.5]), but more propofol (median 529 [424, 672] vs. 100 [100, 130] mg). Noninferiority was detected for all four outcomes; one-tailed superiority tests for each outcome were highly significant at P<0.001 in the expected directions. Conclusions The combination of propofol anesthesia with ultrasound-assisted paravertebral block reduces intraoperative volatile anesthetic and opioid requirements, and results in less post operative pain in patients undergoing breast cancer surgery. Trial Registration ClinicalTrial.gov NCT00418457
Objective: To observe the treatment and prognosis of choroid invasion of retinoblastoma (RB) in children. Method: A total of 149 children who had been diagnosed with unilateral RB and received enucleation disclosing tumor invasion to choroid from January 2006 to December 2013 in Beijing Tongren Hospital were recruited in this study. Choroid involvement was classified as massive choroid invasion and focal choroid invasion. Massive choroid invasion was defined as a maximum diameter of invasive tumor focus of 3 mm or more in diameter that might reach the scleral tissue. Focal choroid invasion was defined as a tumor focus of less than 3 mm in diameter without involvement of sclera. The treatment was delivered according to the invasive status of tumor with combination of histopathological high risk factors. The prognosis of different degrees of choroid invasion was observed. They were divided into two groups according to whether the merger of other high histopathologic risk factors, the survival situation was compared. The subjects were followed up for 1 to 9 years (the median follow-up time: 4 years and 1 month). Result: Among the 149 subjects, 90 were boys and 59 were girls. The right eye was affected in 81 patients and the left eye in 68 patients. Sixteen patients died, resulting in an overall survival rate of 89.3%. Among massive choroid invasion in 47 cases, 9 patients experienced disease recurrence and death resulting in a survival rate of 80.9%. While the focal choroid invasion was found in 102 cases, only 7 children had disease relapsed and died resulting in a survival rate of 93.1% which was statistically significant (χ2=5.067, P=0.024). Among 8 patients with massive choroid invasion without pathological high-risk factors, no death occurred, while in other 39 patients with high-risk factors, 9 died with a mortality rate of 23.1%, however, the difference was not statistically significant (Fisher's exact probability method, P=0.323). Among 60 patients with focal choroid invasion without pathological high-risk factors, no death was observed, while among the other 42 patients presenting high-risk factors, 7 of them died with a mortality rate of 16.7% (Fisher's exact probability method, P=0.003). Cox multivariate analysis showed that massive choroid invasion and surgical margin of the optic nerve were influential factors of prognosis. Conclusion: Patients with focal choroid invasion have a low disease recurrence and may not receive adjuvant chemotherapy. Patients with massive choroid invasion without presenting pathological high-risk factors warrant further prospective study to assess whether adjuvant chemotherapy is needed. However chemotherapy is recommended for those with massive choroid invasion presenting with risk factors to avoid the high disease recurrence in such patients.
Abstract Long noncoding ribonucleic acids (LncRNAs) have been found to be involved in the proliferation, apoptosis, invasion, migration, and other pathological processes of triple-negative breast cancer (TNBC). Expression of the lncRNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) has been found to be significantly higher in TNBC than in other subtypes or in normal tissue samples, but the specific mechanism by which AFAP1-AS1 affects the occurrence and development of TNBC is yet to be revealed. In this study, we used Cell Counting Kit-8 (CCK-8), colony formation, wound healing migration, Transwell invasion, and nude mouse xenograft assays to confirm the role of AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. In addition, we performed bioinformatics analyses, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and dual-luciferase reporter assays (dual-LRA) to confirm interaction among AFAP1-AS1, micro-RNA 2110 (miR-2110), and Sp1 transcription factor ( Sp1 ). We found that silencing AFAP1-AS1 and Sp1 or upregulating miR-2110 suppressed the proliferation, migration, and invasion of MDA–MB-231 and MDA–MB-468 cells in vitro as well as tumor growth in vivo. Mechanistically, the dual-LRA highlighted that miR-2110 was an inhibitory target of AFAP1-AS1, and that AFAP1-AS1 functioned as a miR-2110 sponge to increase Sp1 expression. AFAP1-AS1 silencing led to a reduction in Sp1 mRNA and protein levels, which could be reversed by joint transfection with miR-2110 inhibitor. Our findings demonstrated that AFAP1-AS1 could modulate the progression of breast cancer cells and affect tumorigenesis in mice by acting as a miR-2110 sponge, resulting in regulation of Sp1 expression. Therefore, AFAP1-AS1 could play a pivotal role in the treatment of TNBC.
It is well known that different racial groups have significantly different incidence and mortality rates for certain cancers. It has been suggested that biological factors play a major role in these cancer racial disparities. Previous studies on the biological factors contributing to cancer racial disparity have generated a very large number of candidate factors, although there is modest agreement among the results of the different studies. Here, we performed an integrative analysis using genomic data of 21 cancer types from TCGA, GTEx, and the 1000 Genomes Project to identify biological factors contributing to racial disparity in cancer. We also built a companion website with additional results for cancer researchers to freely mine. Our study identified genes, gene families, and pathways displaying similar differential expression patterns between different racial groups across multiple cancer types. Among them, XKR9 gene expression was found to be significantly associated with overall survival for all cancers combined as well as for several individual cancers. Our results point to the interesting hypothesis that XKR9 could be a novel drug target for cancer immunotherapy. Bayesian network modeling showed that XKR9 is linked to important cancer-related genes, including FOXM1, cyclin B1, and RB1CC1 (RB1 regulator). In addition, metabolic pathways, neural signaling pathways, and several cancer-related gene families were found to be significantly associated with cancer racial disparities for multiple cancer types. Single nucleotide polymorphisms (SNPs) discovered through integrating data from the TCGA, GTEx, and 1000 Genomes databases provide biologists the opportunity to test highly promising, targeted hypotheses to gain a deeper understanding of the genetic drivers of cancer racial disparity and cancer biology in general.
Objective
To analyze the clinical and pathological characteristics and the sites of recurrent and metastatic breast cancer after initial treatment, and subsequently guide the precise management and follow-up treatment for these patients.
Methods
The clinical data of 366 patients with metastatic breast cancer were retrospectively analyzed, the most common recurrent and metastatic sites were descriptively analyzed, and the sites of primary relapse and metastasis were summarized.
Results
Of the 79 luminal-A cases, primary solitary metastasis was found most common in lymph node (39.0%) and bone (24.4%); of the 160 luminal-B cases, primary solitary metastasis was most common in lymph node (39.4%), bone (20.2%) and thoracic wall (18.3%); of the 60 Her-2 rich cases, primary solitary metastasis was most common in lymph node (47.1%) and bone (23.5%); of the 67 triple-negative cases, primary solitary metastasis occurred mostly in lymph node (28.0%) and lung (24.0%).
Conclusions
The most common recurrent and metastatic sites for breast cancer patients were lymph nodes, bone, liver, lung and brain and differs in different breast cancer subtypes. For luminal-A and luminal-B breast cancers, lymph node and bone were the most common recurrent and metastasis sites. In triple negative breast cancer patients, lung is also one of the most common sites of metastasis. Therefore, patients' follow-up check after adjuvant treatment should not only include monitoring lymph node status, but also check-up for lung, bone and brain, which facilitate early diagnosis of relapse and metastases.
Key words:
Recurrent and metastasis of breast cancer; Sites of metastases; Follow-up
To approach the expressions of estrogen receptor (ER),progestogen receptor (PR),Cerb-B2,and Ki67 index in simple mucinous carcinoma of the breast and their clinical significance.The clinicopathological data of 72 patients with simple mucinous carcinoma of the breast who were treated in our hospital from 1997 to 2012 were retrospectively studied. Expressions of ER,PR,Cerb-B2,and Ki67 index and their relationship with clinical characteristics were analyzed.Nine patients had lymph node metastasis. Expressions of ER,PR,and Cerb-B2 were 77.8%,69.4%,and 3.1%,respectively. The expressions of ER,PR,and Cerb-B2 showed no correlation with age,menstrual status,and axillary lymph node metastasis (P>0.05). The expression of ER was correlated with tumor diameter (P=0.008) while the expression of PR and Cerb-B2 showed no such correlation.High ER or PR expression and low Cerb-B2 expression predict good prognosis in patients with simple mucinous carcinoma of the breast. Combined detection of ER,PR,Cerb-B2,and Ki67 index may help to improve the multidisciplinary management of simple mucinous carcinoma of the breast.
To explore the presenting clinical features, management approach and treatment outcomes for occult breast cancer.Twenty-three patients with occult breast cancer presenting with axillary nodal metastases treated in our department between 1986 and 2007 were included in this study. The clinicopathological, imaging and follow-up data of the 23 cases were retrospectively analyzed.All patients were female. The mean age of diagnosis was 57.7 years with a range of 27 - 73 years. The mean follow-up was 15.70 months (range 1 - 62 months). Eight cases in 17 patients were positive by breast ultrasound, three cases in 9 patients were positive by mammography, one case in 2 patients was positive by breast MRI. 20 patients underwent modified radical mastectomy and three patients did not receive the mastectomy treatment. 16 patients had chemotherapy, four patients had radiotherapy, two patients had both chemotherapy and radiotherapy. Two patients had pulmonary metastasis, one patient had recurrence of axillary nodes, pulmonary metastasis and bone metastasis during follow-up.A normal check before operation to exclude a cancer of other origin can help to diagnose occult breast cancer. The breast must be treated. Axillary nodal dissection and mastectomy, or breast conservation with radiation therapy alone can be considered as a management option.
Abstract Background: Few data exist to elucidate sentinel lymph node (SLN) status in breast cancer patients who have a suspicious axillary lymph node (ALN) at ultrasound but a negative clinical physical examination. This study compared various ALN statuses in the breast cancer patients who have a suspicious axillary lymph node (ALN) at ultrasound but a negative clinical physical examination to guide further ALN management. Methods: From Jan 1st 2014 to Jan 1st 2019 in PUMCH (Peking Union Medical College & Hospital), breast cancer patients who had a suspicious axillary lymph node (ALN) at ultrasound but a negative clinical physical examination and treated with sentinel lymph node (SLN) biopsy were retrospectively analyzed. The SLN status, and SLN positive rate in the entire population were analyzed. Lymph node ultrasound and pathological characteristics were compared between patients with positive SLNs and negative SLNs. Results: A total of 483 breast cancer patients (365 SLN negative and 118 SLN positive) were eligible for the final analysis, the SLN positive rate in the enrolled entire population was 32.33%, while in DCIS (Ductal carcinoma in situ) subgroup the SLN positive rate was 12.26%. The patients’ lymph node ultrasound and basic clinical pathological characteristics are listed in table 1. The histology type (P = 0.000), ultrasound lymph node shape (P = 0.000), ultrasound lymph node CMD (corticomedullary demarcation) (P = 0.000), ultrasound lymph node blood flow (P = 0.034) and PR status (P=0.004) had statistical significance between the positive SLNs group and negative SLNs group. Conclusions: 1/3 patients with a suspicious ALN at ultrasound but a negative clinical physical examination had ALN metastasis. IDC, PR positive, ultrasound LN with irregular shape, unclear CMD and blood flow are more likely to have positive SLN. Table 1. Lymph node ultrasound and basic clinical pathological characteristics between SLN negative and positive groupSLN negativeSLN positiveP valuen=365n=118Age(Year)50.14±11.6848.19±10.420.088Histology Type0.000DCIS10613IDC259105Ki67(%)30.69±24.3131.02±23.260.898Ultra-LN Size (cm)1.42±0.691.30±0.730.111Ultra-LN Shape0.000regular359108irregular610Ultra-LN CMD0.000clear32690unclear3928Ultra-LN Blood0.034presence21155absence15463T stage0.071I22779II13133III76ER0.141positive26694negative9924PR0.004positive23292negative13326Her20.067positive10925negative25693Abbreviation:DCIS (Ductal carcinoma in situ); IDC (Invasive ductal carcinoma); Ultra-LN (Ultrasound of lymph node); Ultra-LN CMD (Corticomedullary demarcation in lymph node ultrasound); Ultra-LN Blood (Blood flow in lymph node ultrasound). Citation Format: Xuefei Wang, Shafei Wu, Guochao Zhang, Jiaxin Li, Jianhua Du, Yidong Zhou, Feng Mao, Yan Lin, Songjie Shen, Xiaohui Zhang, Qiang Sun. Comparison of lymph node ultrasound and pathological characteristics of breast cancer patients with positive and negative sentinel lymph node [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-13.
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