Primary acinic cell carcinoma of the breast: A case report and literature review.

Acinic cell carcinoma (ACCA), a type of malignant epithelial neoplasm, tends to occur in the parotid gland, and is occasionally found within the breast. Published literature regarding primary ACCA of the breast is scarce, and the number of reports may be fewer than 100. At present, full clinical details have not been published. As an extremely rare disorder, ACCA cannot be definitively diagnosed depending on microscopic structure alone and often requires the assistance of immunohistochemistry. Currently, universal therapies are not available. Here, we present a 47-year-old patient with a history of a palpable mass in the outer upper quadrant of the left breast for more than 2 years, which had obviously increased in size in the last half year. This patient was definitively diagnosed with primary ACCA of the breast. Neoadjuvant chemotherapy was performed preoperatively, and drug sensitivity tests based on primary tumor cells were conducted after surgery and successfully screened chemotherapy schemes for the patient's greater benefit. The whole treatment course followed the guidelines for invasive breast cancer. The patient was free of symptoms for 14 months after surgery. Long-term follow-up is in progress. Altogether, to further broaden the understanding of primary ACCA of the breast, we detail the diagnosis and treatment of one patient and review the relevant literature.

Integrative multi-omics analyses unravel the immunological implication and prognostic significance of CXCL12 in breast cancer.

Background: CXCL12 is a vital factor in physiological and pathological processes, by inducing migration of multiple cells. We aimed to comprehensively detect the role of CXCL12 in breast cancer, and explore novel CXCL12-related biomarkers through integrative multi-omics analyses to build a powerful prognostic model for breast cancer patients. Methods: Immunohistochemistry analysis of the tissue microarray was performed to evaluate the correlation between CXCL12 expression levels and breast cancer patient outcomes. Combined single-nucleus and spatial transcriptomics data was used to uncover the expression distribution of CXCL12 in breast cancer microenvironment. CXCL12-related genes were identified by WGCNA analysis. Univariate Cox and LASSO regression analyses were then conducted to screen prognostic genes from above CXCL12-related genes, followed by the construction of the CXCL12-related prognostic signature, identification of risk groups, and external validation of the prognostic signature. Analyses of biological function, mutation landscape, immune checkpoint genes and immune cells, were performed to further reveal the differences between high/low-risk groups. Paired single-cell RNA-seq and bulk RNA-seq were analyzed to further disclose the association between the risk score and the complex tumor immune microenvironment. To screen potential therapeutic agents for breast cancer patients, analyses of gene-drug correlation and sensitivity to immunotherapy were conducted. Results: High expression of CXCL12 was linked with a prolonged survival in breast cancer. A total of 402 genes were identified by WGCNA analysis and 11 genes, covering VAT1L, TMEM92, SDC1, RORB, PCSK9, NRN1, NACAD, JPH3, GJA1, BMP8B and ADAMTS2, were screened as the candidate prognostic genes. Next, the prognostic signature was built and validated using these genes to predict the outcomes of breast cancers. The high-risk group patients exhibited significantly inferior prognoses. The combination of the risk score and tumor mutational burden (TMB) had remarkably improved performance in predicting patient outcomes. Besides, high-risk group patients showed higher infiltration of M2-like macrophages. Finally, several potential anticancer drugs were identified. The high-risk group patients were more sensitive to immunotherapy but resistant to docetaxel. Conclusions: CXCL12 has important immunological implication and prognostic significance in breast cancer. The CXCL12-related prognostic model could well predict the prognosis and treatment response of breast cancers.

Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression and chemoresistance by enhancing the secretion of chemotherapy-induced senescence-associated secretory phenotype via activation of DNA damage response pathway.

Senescence frequently occurs in cancer cells in response to chemotherapy (called therapy-induced senescence). Senescent cells can exert paracrine effects through the senescence-associated secretory phenotype (SASP) promoting cancer recurrence and chemoresistance. The altered gut microbiota has been closely associated with cancer progression through the direct interaction with cancer cells. However, little is known about the relationship between the gut microbiota and therapy-induced senescent cells. This study aimed to explore the impact of the gut microbiota on therapy-induced senescent cells and the SASP. We found that esophageal squamous cell carcinoma (ESCC) cells were induced into senescence following platinum-based chemotherapy, accompanied by the secretion of a robust SASP. Furthermore, senescent ESCC cells exerted a tumor-promoting effect through the SASP both in vitro and in vivo. Through 16S rRNA gene sequencing and fluorescence in situ hybridization, we identified that Fusobacterium nucleatum (F. nucleatum) was abundant in human ESCC cancerous tissues and correlated with poor prognosis in ESCC patients. Notably, F. nucleatum further promoted the secretion of the SASP by senescent ESCC cells. Compared with the conditioned medium from senescent ESCC cells, the conditioned medium from F. nucleatum-treated senescent ESCC cells accelerated tumor growth in xenograft models, enhanced migration and invasion abilities, and potentiated chemoresistance both in vitro and in vivo. Mechanistically, F. nucleatum invaded and survived in senescent ESCC cells and induced an increase in DNA damage to further activate the DNA damage response pathway, thus enhancing the SASP. Altogether, these findings reveal for the first time that F. nucleatum promotes the secretion of chemotherapy-induced SASP to drive ESCC progression and chemoresistance, which supports F. nucleatum as a potential target for ESCC therapy.

Adipose tissue macrophages: implications for obesity-associated cancer.

Obesity is one of the most serious global health problems, with an incidence that increases yearly and coincides with the development of cancer. Adipose tissue macrophages (ATMs) are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression. However, the functions of ATMs on the progression of obesity-associated cancer remain unclear. In this review, we describe the origins, phenotypes, and functions of ATMs. Subsequently, we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment, including the direct exchange of dysfunctional metabolites, inordinate cytokines and other signaling mediators, transfer of extracellular vesicle cargo, and variations in the gut microbiota and its metabolites. A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.

Clinical and prognosis value of the number of metastatic lymph nodes in patients with papillary thyroid carcinoma.

OBJECTIVE: It has been reported that papillary thyroid carcinoma (PTC) patients with lymph node metastasis (LNM) are largely associated with adverse outcomes. The present study aimed to assess the correlation between the number of metastatic lymph nodes (NMLNs) and clinical prognosis in patients with PTC. METHODS: We retrospectively reviewed the medical records of patients with PTC who underwent initial thyroid cancer surgery in Renmin Hospital of Wuhan University between 2017 and 2019. A total of 694 patients with PTC and cervical lymph node dissection as well as a total checked number of lymph nodes ≥ 5 were involved in this study. The clinicopathological characteristics of patients were compared according to NMLNs, the number of central cervical lymph nodes (CLNs) and the number of lateral lymph nodes (LLNs). RESULTS: NMLNs > 5, CLNs > 5 and LLNs > 5 were 222 (32.0%), 159 (24.3%) and 70 (10.1%) seen in the analyzed samples, respectively. Young patients, patients with larger tumor diameter, bilaterality, multifocality and gross extrathyroidal extension (ETE) were more inclined to NMLNs > 5, CLNs > 5 and LLNs > 5 (P < 0.05). It was found that the recurrence-free survival among pN1 patients was significantly discrepant between different groups (NMLNs ≤ 5/5: P = 0.001; LLNs ≤ 5/5: P < 0.001). In multivariate logistic regression analysis, patients aged < 55 years (OR = 1.917), primary tumor size > 10 mm (OR = 2.131), bilaterality (OR = 1.889) and tumor gross ETE (OR = 2.759) were independent predictors for high prevalence of total NMLNs > 5 (P < 0.05). Specially, patients aged < 55 years (OR = 2.864), primary tumor size > 10 mm (OR = 2.006), and tumor gross ETE (OR = 2.520) were independent predictors for high prevalence of CLNs > 5 (P < 0.01); Bilaterality (OR = 2.119), CLNs > 5 (OR = 6.733) and tumor gross ETE (OR = 4.737) were independent predictors for high prevalence of LLNs > 5 (P < 0.05). CONCLUSIONS: In conclusion, it is evident that NMLNs is related to the invasive clinicopathological features and adverse outcome of patients with PTC which should be correctly evaluated to provide an appropriate guidance for reasonable treatment and careful follow-up.

Bacteria Associated with Granulomatous Lobular Mastitis and the Potential for Personalized Therapy.

Granulomatous lobular mastitis (GLM), also known as idiopathic granulomatous mastitis (IGM), is a chronic inflammatory lesion of the breast. The incidence of GLM has been increasing in recent years, especially among young women. The etiologies of GLM have not been fully elucidated but are associated with autoimmunity and bacterial infection. Bacteria, especially Corynebacterium species, play important roles in GLM. In this article, we review research progress regarding the bacteriology of GLM attained with the application of several new high-throughput detection techniques. Accurate detection might be important for deepening our understanding of the pathogenesis of GLM and hold promise for personalized GLM therapy.

New Insights of Corynebacterium kroppenstedtii in Granulomatous Lobular Mastitis based on Nanopore Sequencing.

BACKGROUND: The etiology of granulomatous lobular mastitis (GLM) remains unknown. This study aimed to detect bacteria in GLM using Nanopore sequencing and identify the relationship between GLM and Corynebacterium kroppenstedtii. METHODS AND MATERIALS: The bacterial detection on fresh samples (including breast pus and tissue) of 50 GLM patients using nanopore sequencing and culture methods. The bacterial detection rate of participants with different stages were compared and analyzed. Formalin-fixed and paraffin-embedded (FFPE) tissues from 39 patients were performed on Gram staining to identify Gram-positive bacilli (GPB) within lipid vacuoles. Moreover, the clinicopathological characteristics of GLM patients in different bacterial subgroups were also conducted. RESULTS: In 50 GLM patients, the detection rate of bacteria was 78% using nanopore sequencing method, especially in the early stage of GLM (over 80%), which was significantly higher than that using culture methods (24%, p < 0.001). The dominant bacteria were Corynebacterium species (64%), especially for the Corynebacterium kroppenstedtii. The detection rate of C. kroppenstedtii in nanopore sequencing method (56%) was higher than that in culture methods (16%, p < 0.001). Gram staining positive of bacteria in 7 patients, and 5 of them were C. kroppenstedtii. Thirty-one patients (31/39, 79.5%) exhibited typical histological structure of cystic neutrophilic granulomatous mastitis (CNGM), and eighteen patients detected with C. kroppenstedtii. CONCLUSION: Nanopore sequencing showed rapid and accurate bacteria detection over culture method in GLM patients. GLM is not sterile inflammation and closely related to C. kroppenstedtii. CNGM was associated with Corynebacterium infection, especially for C. kroppenstedtii.

Computerized Assessment of the Tumor-stromal Ratio and Proposal of a Novel Nomogram for Predicting Survival in Invasive Breast Cancer.

Background: Various studies have verified the prognostic significance of the tumor-stromal ratio (TSR) in several types of carcinomas using manually assessed H&E stained histologic sections. This study aimed to establish a computerized method to assess the TSR in invasive breast cancer (BC) using immunohistochemistry (IHC)-stained tissue microarrays (TMAs), and integrate the TSR into a novel nomogram for predicting survival. Methods: IHC-staining of cytokeratin (CK) was performed in 7 prepared TMAs containing 240 patients with 480 invasive BC specimens. The ratio of tumor areas and stromal areas was determined by the computerized method, and categorized as stroma-low and stroma-high groups using the X-tile software. The prognostic value of the TSR at 5-year disease free survival (5-DFS) in each subgroup was analyzed. Univariate and multivariate analyses were performed and a novel nomogram for predicting survival in invasive breast cancer was established and assessed. Results: The newly developed computerized method could accurately recognize CK-labeled tumor areas and non-labeled stromal areas, and automatically calculate the TSR. Stroma-low and stroma-high accounted for 38.8% (n = 93) and 61.2% (n = 147) of the cases, according to the cut-off value of 55.5% for stroma ratio. The Kaplan-Meier analysis showed that patients in the stroma-high group had a worse 5-DFS compared to patients in the stroma-low group (P = 0.031). Multivariable analysis indicated that the T stage, N status, histological grade, ER status, HER-2 gene, and the TSR were potential risk factors of invasive BC patients, which were included into the nomogram (P < 0.10 for all). The nomogram was well calibrated to predict the probability of 5-DFS and the C-index was 0.817, which was higher than any single predictor. A dynamic nomogram was built for convenient use. The area under the curve (AUC) of the nomogram was 0.870, while that of the TNM staging system was 0.723. The Kaplan-Meier analysis showed that the nomogram had a better risk stratification for invasive BC patients than the TNM staging system. Conclusions: Based on IHC staining of CK on TMAs, this study successfully developed a computerized method for TSR assessment and established a novel nomogram for predicting survival in invasive BC patients.

EGB761 ameliorates chronic cerebral hypoperfusion-induced cognitive dysfunction and synaptic plasticity impairment.

Chronic cerebral hypoperfusion (CCH) may lead to the cognitive dysfunction, but the underlying mechanisms are unclear. EGB761, extracted from Ginkgo biloba and as a phytomedicine widely used in the world, has been showed to have various neuroprotective roles and mechanisms, and therapeutic effects in Alzheimer's disease and other cognitive dysfunctions. However, improvements in cognitive function after CCH, following treatment with EGB761, have not been ascertained yet. In this study, we used the behavior test, electrophysiology, neurobiochemistry, and immunohistochemistry to investigate the EGB761's effect on CCH-induced cognitive dysfunction and identify its underlying mechanisms. The results showed that EGB761 ameliorates spatial cognitive dysfunction occurring after CCH. It may also improve impairment of the long-term potentiation, field excitable potential, synaptic transmission, and the transmission synchronization of neural circuit signals between the entorhinal cortex and hippocampal CA1. EGB761 may also reverse the inhibition of neural activity and the degeneration of dendritic spines and synaptic structure after CCH; it also prevents the downregulation of synaptic proteins molecules and pathways related to the formation and stability of dendritic spines structures. EGB761 may inhibit axon demyelination and ameliorate the inhibition of the mTOR signaling pathway after CCH to improve protein synthesis. In conclusion, EGB761 treatment after CCH may improve spatial cognitive function by ameliorating synaptic plasticity impairment, synapse degeneration, and axon demyelination by rectifying the inhibition of the mTOR signaling pathway.

Postoperative Onset and Detection of SARS-CoV-2 in Surgically Resected Specimens From Gastrointestinal Cancer Patients With Pre/Asymptomatic COVID-19.

OBJECTIVE: To describe the epidemiologic features and clinical courses of gastrointestinal cancer patients with pre/asymptomatic COVID-19 and to explore evidence of SARS-CoV-2 in the surgically resected specimens. SUMMARY BACKGROUND DATA: The advisory of postponing or canceling elective surgeries escalated a worldwide debate regarding the safety and feasibility of performing elective surgical procedures during this pandemic. Limited data are available on gastrointestinal cancer patients with pre/asymptomatic COVID-19 undergoing surgery. METHODS: Clinical data were retrospectively collected and analyzed. Surgically resected specimens of the cases with confirmed COVID-19 were obtained to detect the expression of ACE2 and the presence of SARS-CoV-2. RESULTS: A total of 52 patients (male, 34) with a median age 62.5 years were enrolled. All the patients presented no respiratory symptoms or abnormalities on chest computed tomography before surgery. Six patients (11.5%) experienced symptom onset and were confirmed to be COVID-19. All were identified to be preoperatively pre/asymptomatic, as 5 were with SARS-CoV-2 presenting in cytoplasm of enterocytes or macrophages from the colorectal tissues and 1 had symptom onset immediately after surgery. The case fatality rate in patients with COVID-19 was 16.7%, much higher than those without COVID-19 (2.2%). CONCLUSIONS: Gastrointestinal cancer patients with pre/asymptomatic COVID-19 were at high risk of postoperative onset and death. At current pandemic, elective surgery should be postponed or canceled. It highlights the need for investigating the full clinical spectrum and natural history of this infection. The early colorectal tropism of SARS-CoV-2 may have major implications on prevention, diagnosis, and treatment of COVID-19.

MET exon 14 skipping mutation, amplification and overexpression in pulmonary sarcomatoid carcinoma: A multi-center study.

BACKGROUND: High frequency of MNNG HOS transforming (MET) exon 14 skipping mutation (MET exon 14Δ) has been reported in pulmonary sarcomatoid carcinomas (PSCs). However, the frequencies differ greatly. Our study aims to investigate the frequency of MET alterations and the correlations among MET exon 14Δ, amplification, and protein overexpression in a large cohort of PSCs. MET exon 14Δ, amplification, and protein overexpression were detected in 124 surgically resected PSCs by using Sanger sequencing, fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) respectively. MET exon 14Δ was identified in 9 (7.3%) of 124 cases, including 6 pleomorphic carcinomas, 2 spindle cell carcinomas and 1 carcinosarcoma. MET amplification and protein overexpression were detected in 6 PSCs (4.8%) and 25 PSCs (20.2%), respectively. MET amplification was significantly associated with overexpression (P < 0.001). However, MET exon 14Δ has no correlation with MET amplification (P = 0.370) and overexpression (P = 0.080). Multivariable analysis demonstrated that pathologic stage (hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.28-6.01; P = 0.010) and MET amplification (HR, 4.71; 95% CI, 1.31-16.98; P = 0.018) were independent prognostic factors for poor median overall survival (mOS). MET alterations including MET exon 14Δ and amplification should be recommended as routine clinical testing in PSCs patients who may benefit from MET inhibitors. MET IHC appears to be an efficient screen tool for MET amplification in PSCs.

Prognostic Significance of the Tumor-Stromal Ratio in Invasive Breast Cancer and a Proposal of a New Ts-TNM Staging System.

BACKGROUND: Previous studies have demonstrated that the tumor-stromal ratio (TSR) was an independent prognostic factor in several types of carcinomas. This study aimed at exploring the prognostic significance of the TSR in invasive breast cancer using immunohistochemistry (IHC)-stained tissue microarrays (TMAs) and integrating the TSR into the traditional tumor-node-metastasis (TNM) staging system. METHODS: The prepared 7 TMAs containing 240 patients with 480 invasive BC specimens were stained with cytokeratin (CK) by the IHC staining method. The ratio of tumor cells and stromal cells was visually assessed. TSR > 1 and TSR ≤ 1 were categorized as the high TSR (low stroma) and low TSR (high stroma) groups, respectively, and the prognostic value of the TSR at 5-year disease-free survival (5-DFS) was analyzed. A new Ts-TNM (tumor stroma-tumor-node-metastasis) staging system was established and assessed. RESULTS: IHC staining of CK could specifically label tumor cells with clear contrast, making it easy to manually assess TSR. High TSR (low stroma) and low TSR (high stroma) were observed in 52.5% (n = 126) and 47.5 (n = 114) of the cases, according to the division of value 1. A Kaplan-Meier analysis showed that patients in the low TSR group had a worse 5-DFS compared with patients in the high TSR group (P=0.022). Multivariable analysis indicated that the T stage (P=0.014), N status (P < 0.001), histological grade (P < 0.001), estrogen receptor status (P=0.015), and TSR (P=0.011) were independent prognostic factors of invasive BC patients. The new Ts-TNM staging system combining TSR, tumor staging, lymph node status, and metastasis staging was established. The receiver operating characteristic (ROC) curve analysis demonstrated that the ability of the Ts-TNM staging system to predict recurrence was not lower than that of the TNM staging system. CONCLUSIONS: This study confirms that the TSR is a prognostic indicator for invasive breast cancer. The Ts-TNM staging system containing stromal and tumor information may optimize risk stratification for invasive breast cancer.

Pulmonary pathology of early-phase COVID-19 pneumonia in a patient with a benign lung lesion.

AIMS: An ongoing outbreak of 2019 novel coronavirus (CoV) disease (COVID-19), caused by severe acute respiratory syndrome (SARS) CoV-2, has been spreading in multiple countries. One of the reasons for the rapid spread is that the virus can be transmitted from infected individuals without symptoms. Revealing the pathological features of early-phase COVID-19 pneumonia is important for understanding of its pathogenesis. The aim of this study was to explore the pulmonary pathology of early-phase COVID-19 pneumonia in a patient with a benign lung lesion. METHODS AND RESULTS: We analysed the pathological changes in lung tissue from a 55-year-old female patient with early-phase SARS-CoV-2 infection. In this case, right lower lobectomy was performed for a benign pulmonary nodule. Detailed clinical, laboratory and radiological data were also examined. This patient was confirmed to have preoperative SARS-CoV-2 infection by the use of real-time reverse transcription polymerase chain reaction and RNA in-situ hybridisation on surgically removed lung tissues. Histologically, COVID-19 pneumonia was characterised by exudative inflammation. The closer to the visceral pleura, the more severe the exudation of monocytes and lymphocytes. Perivascular inflammatory infiltration, intra-alveolar multinucleated giant cells, pneumocyte hyperplasia and intracytoplasmic viral-like inclusion bodies were seen. However, fibrinous exudate and hyaline membrane formation, which were typical pulmonary features of SARS pneumonia, were not evident in this case. Immunohistochemical staining results showed an abnormal accumulation of CD4+ helper T lymphocytes and CD163+ M2 macrophages in the lung tissue. CONCLUSION: The results highlighted the pulmonary pathological changes of early-phase SARS-CoV-2 infection, and suggested a role of immune dysfunction in the pathogenesis of COVID-19 pneumonia.

DNA Methylation Markers for Breast Cancer Detection in the Developing World.

PURPOSE: An unmet need in low-resource countries is an automated breast cancer detection assay to prioritize women who should undergo core breast biopsy and pathologic review. Therefore, we sought to identify and validate a panel of methylated DNA markers to discriminate between cancer and benign breast lesions using cells obtained by fine-needle aspiration (FNA).Experimental Design: Two case-control studies were conducted comparing cancer and benign breast tissue identified from clinical repositories in the United States, China, and South Africa for marker selection/training (N = 226) and testing (N = 246). Twenty-five methylated markers were assayed by Quantitative Multiplex-Methylation-Specific PCR (QM-MSP) to select and test a cancer-specific panel. Next, a pilot study was conducted on archival FNAs (49 benign, 24 invasive) from women with mammographically suspicious lesions using a newly developed, 5-hour, quantitative, automated cartridge system. We calculated sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) compared with histopathology for the marker panel. RESULTS: In the discovery cohort, 10 of 25 markers were selected that were highly methylated in breast cancer compared with benign tissues by QM-MSP. In the independent test cohort, this panel yielded an AUC of 0.937 (95% CI = 0.900-0.970). In the FNA pilot, we achieved an AUC of 0.960 (95% CI = 0.883-1.0) using the automated cartridge system. CONCLUSIONS: We developed and piloted a fast and accurate methylation marker-based automated cartridge system to detect breast cancer in FNA samples. This quick ancillary test has the potential to prioritize cancer over benign tissues for expedited pathologic evaluation in poorly resourced countries.

Experimental evidence of good efficacy and reduced toxicity with peptide-doxorubicin to treat gastric cancer.

BACKGROUND: To compare the efficacy and toxicity of peptide-doxorubicin (PDOX) and doxorubicin (DOX) on nude mice models of human gastric cancer. RESULTS: Both PDOX and DOX could significantly inhibit tumor growth compared with Control (P < 0.05) in both subcutaneous and orthotopic models. Animal survival was much better in PDOX group than DOX group. In peripheral blood test, PDOX group had significantly higher levels of platelets than the Control (P < 0.05), and lymphocyte lower than Control (P < 0.05). There were no significant differences on liver, kidney and cardiac function parameters among three groups (P > 0.05). Immunohistochemistry showed that treatment groups had much higher Tunel than Control (P < 0.05), and PDOX had significantly lower Ki-67 than doxorubicin and Control group (P < 0.01). Western blotting showed that PDOX caused much higher expressions of P53, P21, Aparf-1, pro- and cleaved-caspase 3, compared with DOX. CONCLUSION: Compared with DOX, PDOX has increased effects but much decreased toxicity in treating animal model of gastric cancer. MATERIALS AND METHODS: Animals in subcutaneous model were randomized into Control, doxorubicin, PDOX-L, PDOX-M, and PDOX-H groups. Animals in surgical orthotopic implantation model were randomized into Control, doxorubicin and, peptide-doxorubicin groups. The animals were treated, monitored and examined following a set protocol.

Efficacy of EGFR tyrosine kinase inhibitors in non-small cell lung cancer patients harboring different types of EGFR mutations: A retrospective analysis.

With the development of molecular pathology, many types of epidermal growth factor receptor (EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations (co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate (DCR) was 93.7% with two patients (0.2%) achieving complete response (CR), the median progression free survival (PFS) was 13.0 months (95% confidence interval [CI], 11.6-14.4 months), and the median overall survival (OS) was 55.0 months (95% CI, 26.3-83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858R mutation (P<0.001). Patients with classic mutations (del-19 and/or L858R mutations) demonstrated longer PFS (P<0.001) and OS (P=0.017) than those with uncommon mutations (single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS (hazard ratio [HR]=0.308, 95% CI, 0.191-0.494, P<0.001) and OS (HR=0.221, 95% CI, 0.101-0.480, P<0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations (especially for the patients with single rare mutations) are needed to determine a better precision treatment.

The association between prognosis of breast cancer and first-degree family history of breast or ovarian cancer: a systematic review and meta-analysis.

Whether a positive family history of breast cancer or ovarian cancer (FHBOC) would affect the prognosis of breast cancer is still up for debate and further study. This meta-analysis was performed to clarify this issue. We reviewed two databases (PubMed and CNKI) for research articles published at any time from the inception of these databases to April 1, 2016 for articles detecting the impact of FHBOC on the prognosis of breast cancer. A meta-analysis was conducted to generated combined hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS) and breast cancer-specific survival (BCSS). Eighteen studies were included in our qualitative analysis, with 15 studies ultimately part of the quantitative analysis. The pooled results demonstrated that a positive FHBOC was associated with better OS (0.89, 95% CI 0.83-0.95) and BCSS (0.90, 95% CI 0.82-0.99). In subgroup analyses, several subgroups (maximally adjusted studies, population based studies, high quality studies, family history of breast cancer, studies from Europe, studies from Asia, 1 affected relative, or tumor size > 2 cm), a positive first-degree FHBOC was associated with better prognosis of breast cancer. Notably, for those patients who underwent breast-conserving surgery, first-degree FHBOC was not a risk factor for OS (HR 1.08, 95% CI 0.53-2.21). Our meta-analysis demonstrated that a first-degree FHBOC was associated with better OS and BCSS in patients with breast cancer. These findings support that clinical management should not differ between women with and without FHBOC.

Family history of cancer other than breast or ovarian cancer in first-degree relatives is associated with poor breast cancer prognosis.

OBJECTIVE: Whether a first-degree family history of others cancers (FHOC) than breast or ovarian cancer (BOC) is associated with breast cancer prognosis remains unknown. Thus, the aim of the present study was to clarify this issue. METHODS: Women who were diagnosed with invasive breast cancer at the Renmin Hospital of Wuhan University from 2010 to 2013 were included in the study. The demographic and clinicopathological characteristics of these patients were extracted. FHOC was considered positive for any patient who had a relative who had been diagnosed with cancer other than BOC. Disease-free survival (DFS) was calculated based on the date of diagnosis. DFS was analyzed using the Cox proportional hazards model. RESULTS: A total of 434 breast cancer patients were included in this study. Among these patients, 61 (14.06%) had a positive FHOC in first-degree relatives. Patients with a positive FHOC tended to have HER2-positive breast cancer (p = 0.03). In the survival analysis, FHOC was associated with poor DFS in both univariate (HR = 2.21 (1.28-3.83), 95% CI: 1.28-3.83, p < 0.01) and multivariate (HR = 2.50, 95% CI: 1.24-5.04, p = 0.01) analyses, especially in patients with luminal A subtypes. CONCLUSION: The results demonstrated an increased risk of recurrence in breast cancer patients with FHOC, especially in patients with luminal A subtype.

Mucinous variant of invasive micropapillary carcinoma of breast: report of two cases and literature review.

Invasive micropapillary carcinoma (IMPC) is a rare type of malignant tumor of breast with a poor prognosis. There is controversy in the identification of mucinous variant of IMPC with mucinous carcinoma. In the past, it always be diagnosed as micropapillary variant of mucinous carcinoma, but in this study, the author has a different opinion. Here, we report two cases diagnosed as mucinous variant of IMPC. Histological morphologies were similar in the two cases. In difference from mucinous carcinoma, mucinous variant of the IMPC is characterized by micropapillary structure of the tumor cells, higher nuclear atypia, more frequent HER2/Neu overexpression, high proliferation index of Ki-67, increased lymph node metastasis, and poor prognosis. A distinct feature of the 2 cases was that the tumor cells were present as micropapillary or tubular-solid clusters floating in the extracellular mucin pools and most of the floating tumor cells were surrounded by the hyaline lacunae, which can clearly be appreciated even in the background of mucin. Both patients were managed by the standard chemotherapy and radiotherapy combined with simple mastectomy. Up to the time of preparation of this report, both patients have survived for over 4 years. It is important to differentiate a mucinous variants of IMPC from a pure mucinous carcinoma due to their significantly different prognosis and, thereafter, different choices of patient management.