Septin9 DNA methylation is associated with breast cancer recurrence or metastasis.

OBJECTIVE: We aimed to explore the prognostic value of Septin9 DNA methylation in breast cancer. METHODS: Breast cancer patients with and without recurrence or metastasis and matched non-breast cancer patients were screened retrospectively from 2014 to 2016. Bisulfite conversion and fluorescence quantitative methylation-specific polymerase chain reaction were used to detect the Septin9 methylation status and distribution levels in patient breast tissues. RESULTS: Septin9 DNA methylation was more frequent in breast cancer tissues than in non-breast cancer tissues, but was not significantly correlated with any relevant breast cancer patient clinicopathological characteristic. Septin9 methylation rates were higher in patients with recurrence or metastasis. Septin9 methylation, tumor size, lymph node status, and progesterone receptor (PR) expression could influence prognosis. Septin9 methylation was significantly associated with worse disease-free survival in breast cancer patients, with receiver operating characteristic curve analysis indicating that it had good prognostic ability, with an area under the curve (AUC) value of 0.719. The AUC values increased when Septin9 methylation was combined with tumor size, lymph node status, and PR to predict prognosis. CONCLUSIONS: Septin9 DNA methylation was an independent predictors of breast cancer prognostic risk. This could possibly help improve comprehensive prognosis prediction methods when combined with other risk factors.

Use of urinary balloon catheter to prevent postoperative bleeding after ultrasound-guided vacuum-assisted breast biopsy.

Postoperative bleeding is the most frequent serious complications after vacuum-assisted breast biopsy (VABB). The aim of this study was to evaluate the clinical effect of using urinary balloon catheter to prevent postoperative bleeding after ultrasound-guided VABB. From May 2016 to June 2018, 324 patients who underwent ultrasound-guided VABB were randomized into the study group and control group. In the study group, an urinary balloon catheter was inserted into the excision cavity to prevent bleeding and hematoma. In the control group, compression with thorax pressure bandage was used for hemostasis. Postoperative subcutaneous ecchymosis and hematoma were recorded and compared between the two groups. The rates of postoperative ecchymosis and hematoma in the study group were significantly lower than that in the control group (5.6% vs 13.0%, P < .05; 8.0% vs 20.4%, P < .05). Among patients with lesions ≤1.5 cm, the rates of postoperative ecchymosis and hematoma were 2.9% and 4.3% in the study group, 6.5% and 11.7% in the control group, but there was no statistically significant difference between the two groups (P > .05). Among patients with lesions >1.5 cm, the rates of postoperative ecchymosis and hematoma in the study group were significantly lower than that in the control group (7.6% vs 18.8%, P < .05; 10.9% vs 28.2%, P < .05). Hemostasis with balloon urinary catheter is a safe and effective method to prevent postoperative bleeding after VABB.

Dietary choline and betaine intake, choline-metabolising genetic polymorphisms and breast cancer risk: a case-control study in China.

Choline and betaine are essential nutrients involved in one-carbon metabolism and have been hypothesised to affect breast cancer risk. Functional polymorphisms in genes encoding choline-related one-carbon metabolism enzymes, including phosphatidylethanolamine N-methyltransferase (PEMT), choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT), have important roles in choline metabolism and may thus interact with dietary choline and betaine intake to modify breast cancer risk. This study aimed to investigate the interactive effect of polymorphisms in PEMT, BHMT and CHDH genes with choline/betaine intake on breast cancer risk among Chinese women. This hospital-based case-control study consecutively recruited 570 cases with histologically confirmed breast cancer and 576 age-matched (5-year interval) controls. Choline and betaine intakes were assessed by a validated FFQ, and genotyping was conducted for PEMT rs7946, CHDH rs9001 and BHMT rs3733890. OR and 95 % CI were estimated using unconditional logistic regression. Compared with the highest quartile of choline intake, the lowest intake quartile showed a significant increased risk of breast cancer. The SNP PEMT rs7946, CHDH rs9001 and BHMT rs3733890 had no overall association with breast cancer, but a significant risk reduction was observed among postmenopausal women with AA genotype of BHMT rs3733890 (OR 0·49; 95 % CI 0·25, 0·98). Significant interactions were observed between choline intake and SNP PEMT rs7946 (P interaction=0·029) and BHMT rs3733890 (P interaction=0·006) in relation to breast cancer risk. Our results suggest that SNP PEMT rs7946 and BHMT rs3733890 may interact with choline intake on breast cancer risk.

A nomogram based on mammary ductoscopic indicators for evaluating the risk of breast cancer in intraductal neoplasms with nipple discharge.

Mammary ductoscopy (MD) is commonly used to detect intraductal lesions associated with nipple discharge. This study investigated the relationships between ductoscopic image-based indicators and breast cancer risk, and developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge. A total of 879 consecutive inpatients (916 breasts) with nipple discharge who underwent selective duct excision for intraductal neoplasms detected by MD from June 2008 to April 2014 were analyzed retrospectively. A nomogram was developed using a multivariate logistic regression model based on data from a training set (687 cases) and validated in an independent validation set (229 cases). A Youden-derived cut-off value was assigned to the nomogram for the diagnosis of breast cancer. Color of discharge, location, appearance, and surface of neoplasm, and morphology of ductal wall were independent predictors for breast cancer in multivariate logistic regression analysis. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.36. Area under the curve values of 0.812 (95 % confidence interval (CI) 0.763-0.860) and 0.738 (95 % CI 0.635-0.841) was obtained in the training and validation sets, respectively. The accuracies of the nomogram for breast cancer diagnosis were 71.2 % in the training set and 75.5 % in the validation set. We developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge based on MD image findings. This model may aid individual risk assessment and guide treatment in clinical practice.

Screening of significantly hypermethylated genes in breast cancer using microarray-based methylated-CpG island recovery assay and identification of their expression levels.

To screen candidate methylation markers for early detection of breast cancer and to explore the relationship between methylation and gene expression, we performed methylated-CpG island recovery assay (MIRA) combined with CpG island array on 61982 CpG sites across 4162 genes in 10 cancerous and 10 non-cancerous breast tissues. Direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out in independent cancerous and non-cancerous samples. Gene expression was analyzed by microarrays and validated using RT-PCR. We detected 70 significantly hypermethylated genes in breast cancer tissues, including many novel hypermethylated genes such as ITGA4, NFIX, OTX2 and FGF12. Direct bisulfite sequencing showed widespread methylation occurring in intragenic regions of the WT1, PAX6 and ITGA4 genes and in the promoter region of the OTX2 gene in breast cancer tissues. COBRA assay confirmed that the WT1, OTX2 and PAX6 genes were hypermethylated in breast cancer tissues. Clustering analysis of the gene expression of 70 significantly hypermethylated genes revealed that most hypermethylated genes in breast cancer were not expressed in breast tissues. RT-PCR assay confirmed that WT1 and PITX2 were only weakly expressed in the breast cancer tissues and were not expressed in most non-cancerous breast tissues. OTX2 and PAX6 were not expressed in either breast cancer or non-cancerous tissues. In conclusion, these results will expand our knowledge of hypermethylated genes and methylation sites for early detection of breast cancer and deepen our understanding of the relationship between methylation and gene expression. The MIRA approach can screen candidate methylated genes for further clinical validation more effectively than gene expression microarray-based strategy.

[Anti-mycobacteria drugs therapy for periductal mastitis with fistula].

OBJECTIVES: To study the etiology, clinical and pathologic characteristics of periductal mastitis with fistula and estimate the effect of anti-mycobacterial agents for periductal mastitis with fistula. METHODS: Totally 27 patients of periductal mastitis with fistula received anti-mycobacteria drugs therapy from December 2008 to September 2011 were analyzed retrospectively. All of the patients were female. The mean age at onset was 28 years (range 15 to 40 years old). The main clinical manifestation of the 27 patients was breast fistula, including 21 patients with single fistula and 6 patients with multiple fistula. Three patients manifested with pure fistula, 14 patients with both fistula and lump, 10 patients with fistula, lump and abscess. The samples including pus or tissues of all patients were underwent bacteria culture and all patients core needle biopsy. All patients were given primary anti-mycobacteria drugs therapy, parts of patients received surgery based on the evaluation of medical treatment. RESULTS: The common bacteria culture of all patients failed to demonstrate any causative microorganism. Four cases were selected randomly to undergo PCR of mycobacteria, only one case was identified as Massiliense in bacteria culture of mycobacteria. Twenty-seven patients with periductal mastitis with fistula were treated with anti-mycobacterial agents (isoniazid, rifampicin and ethambutol or pyrazinamide of triple oral drugs) for 1 to 3 months, the fistula of all 27 patients were closed well. Sixteen patients were treated with the agents only and cured. Eleven patients received surgical treatment after treated with the medical agents. None of the patients were given mastectomy. All patients had no reccurence until now. CONCLUSIONS: The periductal mastitis with fistula has a closely relationship with the infection of nontuberculosis mycobacteria. Those patients could be treated with triple anti-mycobacterial agents and could also avoided mastectomy.

[The clinical study of high-frequency ultrasound-guided vacuum-assisted biopsy for breast microcalcifications].

OBJECTIVE: To evaluate the clinical application of high-frequency ultrasound-guided vacuum-assisted biopsy for breast microcalcifications. METHODS: Sixty-six patients with 70 lesions of microcalcifications detected at mammography underwent high-frequency ultrasound-guided vacuum-assisted biopsy from July 2009 to October 2010. All patients were female, aged 24 to 61 years (median age 40 years). Among 70 lesions of microcalcifications, unilateral lesions were 62 cases and bilateral lesions were 4 cases. The clinical factors that affected the success of biopsy were investigated by χ(2) test and Logistic regression analysis. RESULTS: Among 70 lesions of microcalcifications, the successful rate of biopsy was 72.9% (51/70). The biopsy successful rate of microcalcifications without and with masses were 65.2% (30/46) and 87.5% (21/34) respectively (χ(2) = 3.960, P = 0.047). The biopsy successful rate of microcalcifications of maximal diameter more than 5 mm was higher than that of maximal diameter less than 5 mm (88.9% vs. 55.9%, χ(2) = 9.633, P = 0.002). The Logistic regression analysis showed that the types and maximal diameter of microcalcifications were the main factors that affected the success of biopsy. CONCLUSION: The clinical application of high-frequency ultrasound-guided vacuum-assisted biopsy was an effective option for the diagnosis of breast microcalcifications, especially for the type of microcalcifications with masses and the maximal diameter more than 5 mm.

Significance of methylene blue dye for localization biopsy of nonpalpable breast lesions.

BACKGROUND AND OBJECTIVE: With advances in mammographic equipment and techniques, more and more nonpalpable breast lesions have been detected. This study was to investigate the application of methylene blue dye for localized biopsy to diagnose nonpalpable breast lesions. METHODS: In total 138 patients with suspicious malignant, nonpalpable breast lesions between August 2002 and October 2006 were enrolled. A small dose of methylene blue was injected into the lesion under mammographic guidance. The dyed tissues were excised completely via an optimal incision, and radiographys was obtained to confirm the removal of the nonpalpable lesion. The specimen weight and incision length were measured. RESULTS: Suspicious lesions in all 138 patients were accurately excised. Eighty-four (60.9%) patients were confirmed as breast cancer, and 54 (39.1) were diagnosed with benign lesions. The mean length of the incision was 4.6 cm (range 3.2-5.3 cm), and the mean weight of the resected specimen was 42 g (range18-86 g). All patients achieved stage I healing. CONCLUSIONS: Excisional biopsy is recommended for nonpalpable breast lesions which are highly suggestive of malignancy by imaging examination. Methylene blue guided localization and excisional biopsy is a safe, relatively simply procedure with high diagnostic accuracy.

[Advancement in endocrine therapy for breast cancer].

Endocrine therapy with certain effect is an important part of combined therapy for hormone receptor-positive breast cancer. The endocrine therapy for breast cancer has made progress with the development of new endocrine drugs. Now, tamoxifen is still the standard endocrine therapeutic drug for the premenopausal patients, but aromatase inhibitors can bring more benefit for the postmenopausal patients. Several large-scale clinical trials about aromatase inhibitors and medical ovarian ablation are ongoing and attract attention widely. This review overviewed the endocrine therapy for breast cancer, and mainly introduced its recent advancement.

[Expression and clinical significance of adhesive molecule CD44v6 in breast invasive ductal carcinoma].

BACKGROUND & OBJECTIVE: Many researches suggest that CD44v6 is associated with the occurrence, invasion, and metastasis of breast cancer. However the reports about the relationship between CD44v6 expression and the prognosis of breast cancer are conflicting. This study was to investigate the expression of CD44v6 and its correlation to clinicopathologic characteristics and prognosis of breast cancer. METHODS: CD44v6 expression in 84 specimens of breast cancer and 20 specimens of para-tumor breast tissues was detected by SP immunohistochemistry. COX proportional hazards model was used to analyze the prognosis. RESULTS: The positive rate of CD44v6 in the epithelial cells of breast cancer was significantly higher than that in para-tumor breast tissues (78.6% vs. 5.0%, P<0.05). The expression of CD44v6 was closely correlated to TNM stage, tumor size, and lymph node metastasis (P<0.05). The median follow-up period was 60 months. The overall survival rate was significantly higher in CD44v6-negative group than in CD44v6-positive group (P<0.05). The survival curve had a tendency to decline with the stronger expression of CD44v6. Cox model revealed that ER, TNM stage, and CD44v6 were independent prognostic factors of breast cancer. CONCLUSIONS: CD44v6 is highly expressed in breast cancer, and positively correlated to TNM stage, tumor size, and lymph node metastasis. CD44v6 is an independent prognostic factor of breast cancer.