Relationship between mammographic calcifications and the clinicopathologic characteristics of breast cancer in Western China: a retrospective multi-center study of 7317 female patients.

BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.

Dual Target of EGFR and mTOR Suppresses Triple-Negative Breast Cancer Cell Growth by Regulating the Phosphorylation of mTOR Downstream Proteins.

Objective: To detect the activation of the EGFR and mTOR signaling pathways in the triple negative breast cancer cell line MDA-MB-468 and investigate the inhibitory effect of gefitinib, an epidermal growth factor receptor inhibitor, and everolimus, a target protein inhibitor of rapamycin, on triple negative breast cancer cells. Methods: Triple negative human breast cancer MDA-MB-468 cells were cultured and blank control group, single EGFR inhibitor gefitinib group, single mTOR inhibitor everolimus group, and two drug combination group were set up respectively to detect the effects of single and combined drugs on cell proliferation activity, cell cycle and apoptosis, and the expression of EGFR and mTOR signal pathway proteins in cell lines after single and combined drug intervention was detected again by Western blot. Results: The level of EGFR and p-mTOR protein in triple negative breast cancer was higher than in non triple negative breast cancer (P<0.05). The level of mTOR, S6K1, p-EGFR, p-S6K1 was significantly increased when treated with EGF (0ng/mL, 10ng/mL, 100ng/mL) for 1h, compared to without EGF stimulation (P<0.05). The level of p-EGFR, p-mTOR, p-S6K1 protein increased significantly when the cells were exposed to EGF for 2h, respectively (P<0.05). EGFR inhibitor gefitinib alone and the mTOR inhibitor everolimus alone could significantly inhibit the proliferation of human triple negative breast cancer MDA-MB-468 cells in a dose-dependent manner (P<0.05). The level of p-4EBP1 protein in EGFR and mTOR signal pathway was significantly increased after the intervention of gefitinib alone, everolimus alone, and the combination of two drugs (P<0.05). Conclusion: EGFR and mTOR signaling pathways can be activated in triple negative breast cancer; Both the EGFR inhibitor gefitinib alone and the mTOR inhibitor everolimus alone can significantly inhibit the proliferation of human triple negative breast cancer MDA-MB-468 cells. The combination of the EGFR inhibitor gefitinib and the mTOR inhibitor everolimus may achieve anti-tumor effect similar to that of single drug by reducing the drug dose.

[Association between single nucleotide polymorphisms of BARD 1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) of BARD1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang. METHODS: A case-control study was designed to explore the genotypes of Pro24Ser (C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene, detected by PCR-restriction fragment length polymorphism (PCR-RFLP) assay, in 144 early-onset breast cancer cases of Uygur women (≤ 40 years) and 136 cancer-free controls matched by age and ethnicity. The association between SNPs of BARD1 gene and risk of early-onset breast cancer in Uygur women was analyzed by unconditional logistic regression model. RESULTS: Early age at menarche, late age at first pregnancy, and positive family history of cancer may be important risk factors of early-onset breast cancer in Uygur women in Xinjiang. The frequencies of genotypes of Pro24Ser (C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene showed significant differences between the cancer cases and cancer-free controls (P < 0.05). Compared with wild-type genotype Pro24Ser CC, it showed a lower incidence of early-onset breast cancer in Uygur women with variant genotypes of Pro24Ser TT (OR = 0.117, 95%CI = 0.058 - 0.236), and dominance-genotype CT+TT (OR = 0.279, 95%CI = 0.157 - 0.494), or Arg378Ser CC (OR = 0.348, 95%CI = 0.145 - 0.834) and Val507Met AA(OR = 0.359, 95%CI = 0.167 - 0.774). Furthermore, SNPS in three polymorphisms would have synergistic effects on the risk of breast cancer. In addition, the SNP-SNP interactions of dominance-genotypes (CT+TT, GC+CC and GA+AA) showed a 52.1% lower incidence of early-onset breast cancer in Uygur women (OR = 0.479, 95%CI = 0.230 - 0.995). Stratified analysis indicated that the protective effect of carrying T variant genotype (CT/TT) in Pro24Ser and carrying C variant genotype (GC/CC) in Arg378Ser were more evident in subjects with early age at menarche and negative family history of cancer. With an older menarche age, the protective effect was weaker. CONCLUSIONS: SNPs of Pro24Ser(C/T), Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene are associated with significantly decreased risk of early-onset breast cancer in Uygur women in Xinjiang. Early age at menarche and negative family history of cancer can enhance the protective effect of mutant allele.

Thyroidectomy Using the Lateral Cervical Small Incision Approach for Early Thyroid Cancer.

Objective: Surgical resection is the main treatment for thyroid cancer, but while traditional open thyroidectomy improves prognosis, it also results in poor cosmetic outcomes. Therefore, we devised the lateral cervical small incision approach to thyroidectomy and will evaluate its efficacy. Methods: The clinicopathological data of 191 patients who underwent unilateral thyroidectomy and isthmusectomy for early thyroid cancer were collected retrospectively. Of these, 100 patients underwent a traditional thyroidectomy using the median cervical approach (control group), and 91 patients underwent a thyroidectomy using the lateral cervical small incision approach (experimental group). The differences in perioperative prognosis, postoperative complications, and cosmetic outcomes between the two groups were evaluated. Results: There was no significant difference in sex, age, tumor size, lymph node dissection, number of metastases, or postoperative complications between the experimental group and the control group (P > 0.05). There were significant differences in the duration of the operation; postoperative blood loss, drainage, and hospital stay; and scar color, blood circulation, hardness, and thickness between the groups (P < 0.05). The cosmetic outcomes of the incisions in the experimental group were more satisfactory than in the control group (P < 0.05). Conclusion: When compared with traditional open thyroidectomy, the lateral cervical small incision approach has a lower incidence of complications, a better perioperative prognosis, and an improved cosmetic outcome.

The role of microRNA-4723-5p regulated by c-myc in triple-negative breast cancer.

The aim of this study was to investigate the expression of miRNA regulated by c-myc and its mechanism in three negative breast cancer (TNBC). We constructed MDA-MB-231 cell line with low expression of c-myc by lentivirus short hairpin RNA (shRNA), analyzed the miRNA expression profile of MDA-MB-231 cell line with different expression levels of c-myc by high-throughput sequencing technology, obtained differential miRNA by bioinformatics analysis and statistical analysis, and verified hsa-mir-4723-5p by Quantitative Real-time polymerase chain reaction(QRT-PCR). The target gene of hsa-mir-4723-5p was analyzed by miRDB and miRWalk database. The results showed that there were significant differences in 126 miRNAs in c-myc knockdown cell lines compared with the control group, of which 84 were significantly up-regulated and 42 were significantly down regulated. According to the results of miRNA sequencing, the miRNA closely related to the expression of c-myc was hsa-mir-4723-5p. QRT PCR showed that the expression of hsa-mir-4723-5p was down regulated in TNBC cell line MDA-MB-231 with low expression of c-myc, which was positively correlated with the expression. The target genes of hsa-mir-4723-5p were predicted according to mirdb and mirwalk database. A total of 112 target genes were obtained, and 107 target genes were related to hsa-mir-4723-5p. Through mirdb and mirwalk databases, it was found that the target gene TRAF4 of hsa-mir-4723-5p may be related to cancer pathway and affect tumor metastasis. In conclusion, the hsa-miR-4723-5p regulated by c-myc may be involved.

The correlation between ultrasonographic features, bFGF, and the local invasiveness of thyroid papillary carcinoma.

The present study aimed to investigate the correlation between ultrasonographic features, basic fibroblast growth factor (bFGF), and the local invasiveness of papillary thyroid carcinoma (PTC).A total of 350 samples of thyroid nodules were collected. Routine ultrasonography was performed before the operation and routine pathological diagnosis and bFGF detection were performed after the operation.'These 350 samples of thyroid nodules included 90 samples of nodular goiter, 36 samples of focal thyroiditis, and 224 samples of PTC. A total of 326 thyroid nodules were examined for bFGF. The results revealed that the difference in the expression of bFGF between the benign and malignant groups was statistically significant (P < .05) and the difference in the positive expression of bFGF between the invasive and non-invasive PTC groups was statistically significant (P < .05).Whether the shape of PTC is regular or not and whether there is micro-calcification in PTC and other ultrasonographic features, the size and location of the lesions and the age of the patient help make a preliminary prediction of local invasiveness before the operation. Postoperative detection of bFGF is helpful for further risk assessments of PTC.

Clinicopathologic and Prognostic Significance of Body Mass Index (BMI) among Breast Cancer Patients in Western China: A Retrospective Multicenter Cohort Based on Western China Clinical Cooperation Group (WCCCG).

INTRODUCTION: Clinicopathologic and prognostic significance of body mass index (BMI) in breast cancer (BC) patients remained conflicting. We aimed to investigate and modify the impact of BMI on clinicopathological significance and survival in western Chinese BC patients. MATERIALS AND METHODS: 8,394 female BC patients from Western China Clinical Cooperation Group (WCCCG) between 2005 and 2015 were identified. Multivariable logistic regression and Cox proportion hazard regressions were used to examine the difference of clinicopathologic and survival characteristics between BMI categories. RESULTS: For the premenopausal, overweight and obese (OW) patients tended to have large tumor size (>5cm) (odds ratio [OR], 1.30, P<0.01) and triple-negative BC (OR, 1.31; P=0.01) compared with normal weight (NW) patients. Premenopausal underweight (UW) patients had a significantly higher risk of HER2 positive (OR, 1.71; P=0.02) and distant metastasis (OR, 2.59; P=0.01). For postmenopausal patients, OW patients showed higher risks of large tumor size (>5cm) (OR, 1.46; P=0.01), nuclear grade III (OR, 1.24; P=0.04), and lymphovascular invasion (OR, 1.46; P=0.01) compared with NW patients. An "U" shaped relationship between BMI and DFS was found (UW versus NW, adjusted hazard ratio (HR), 2.80, P<0.001; OW versus NW, adjusted HR, 1.40, P=0.02), whereas no significant difference of disease-free survival (DFS) between OW and NW premenopausal patients (adjusted HR=1.34, P=0.18) was revealed. CONCLUSION: We concluded that UW and OW were associated with aggressively clinicopathological characteristics, regardless of menopausal status. An "U" shaped association of BMI and DFS was revealed, and no significant difference of DFS between OW and NW in postmenopausal subgroup was revealed.

Predictors of internal mammary lymph nodes (IMLN) metastasis and disease-free survival comparison between IMLN-positive and IMLN-negative breast cancer patients: Results from Western China Clinical Cooperation Group (WCCCG) database (CONSORT).

Limited studies performed a comprehensive assessment of risk factors for internal mammary lymph nodes (IMLN) metastasis, and disease-free survival (DFS) difference between IMLN-positive and IMLN-negative breast cancer (BC) patients undergoing IMLN dissection and systemic therapies was not clear.A retrospective study included 1977 BC patients from Western China Clinical Cooperation Group between January 2005 and December 2012. The impact of clinicopathological factors on the occurrence of IMLN metastasis was assessed in univariate and multivariate logistic regression analyses, and a nomogram (model) was constructed to predict the IMLN status. DFS difference was evaluated in univariate and multivariate Cox regression analyses between IMLN-negative and IMLN-positive patients, and univariate analysis was performed to compare DFS between individuals with high and low IMLN metastasis risk defined by proposed nomogram.Of 1977 enrolled patients, 514 cases underwent IMLN dissection and 1463 cases did not undergo IMLN irradiation or dissection. We found that initial disease symptoms and signs, mammographic calcification, tumor site, number of positive axillary lymph nodes (ALNs), American Joint Committee on Cancer pT stage, and human epidermal growth factor receptor 2 status were associated with IMLN metastasis (all P < .05). Those variables were included in nomogram, whose predictive ability was better than that of ALN classification (area under the curve: 0.82 vs 0.76, P < .001). Univariate cox proportional hazards model indicated that better DFS was observed in IMLN-negative patients than IMLN-positive group (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.05-3.34; P = .04), whereas no significant differences in DFS (HR = 0.99, 95% CI = 0.49-2.00; P = .97) were found after adjusting patient-, disease-, and treatment-related factors.Nipple inversion, mammographic calcification, larger tumor size, medial tumor site, negative HER-2 status, and more positive ALNs are independent risk factors for IMLN metastasis, and the individualized nomogram is a feasible tool to predict the status of IMLN. Equivalent DFS was found between positive and negative IMLN patients who all accepted IMLN dissection and systemic therapies.

Clinicopathologic Factors Related to the Histological Tumor Grade of Breast Cancer in Western China: An Epidemiological Multicenter Study of 8619 Female Patients.

BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2 cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti-HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.

Expression of Spindle and Kinetochore-Associated Protein 1 Is Associated with Poor Prognosis in Papillary Thyroid Carcinoma.

AIM: Spindle and kinetochore-associated protein 1 (SKA1) is one subtype of SKA, whose protein can make spindle microtubules attach steadily to the kinetochore in the middle of mitosis. At present, there are fewer researches on the relationship between SKA1 expression and tumor development. METHODS: In this study, immunohistochemical analysis was used to determine the expression of SKA1 in papillary thyroid carcinoma (PTC) and adjacent tissues. We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis to further verify the results. RESULTS: We found that SKA1 expression was significantly higher in PTC tissues than normal adjacent tissues (P < 0.05). There existed a significant correlation among a higher SKA1 expression, including lymphoid node (P = 0.005), clinical stage (P = 0.015), and extrathyroid invasion (P = 0.004). Survival analysis showed high SKA1 expression in PTC patients more likely to relapse after surgery. CONCLUSION: High SKA1 expression is predictive of poor prognosis of PTC, implying that SKA1 may be a promising new target for targeted therapies for PTC.

Immunohistochemical analysis of phosphorylated mammalian target of rapamycin and its downstream signaling components in invasive breast cancer.

The present study aimed to investigate whether the mammalian target of rapamycin (mTOR) signaling pathway is activated in invasive breast cancer. The expression levels of phosphorylated (p)­mTOR at ser2448 were detected, as well as the expression levels of its downstream signaling molecules: Eukaryotic translation initiation factor 4E­binding protein 1 (4E­BP1), and p70 ribosomal protein S6 kinase 1 (S6K1). The correlation between p­mTOR, p­4E­BP1, p­S6K1, and the clinicopathological parameters of breast cancer were also determined. p­mTOR, p­4E­BP1 and p­S6K1 expression was detected in 285 breast cancer tumor samples and adjacent normal tissue samples using immunohistochemistry. The expression levels and the location of the proteins were analyzed and compared in the various tissue samples. Multivariate Cox regression was used to analyze the clinicopathological factors and prognosis associated with the tissue samples. The disease­free survival rate was examined using survival analyses and Log­rank tests. The results of the present study indicated that the expression levels of p­mTOR, p­4E­BP1, and p­S6K1 were significantly higher in breast cancer tissue, as compared with normal tissue (P<0.01). p­mTOR was predominantly expressed in the cytoplasm, whereas p­4E­BP1 and p­S6K1 were predominantly co­expressed in the cytoplasm and the nucleus. In addition, p­4E­BP1 and p­S6K1 were more likely to be expressed in the cytoplasm in breast cancer tissue samples, as compared with normal tissue samples (P<0.001). Positive p­mTOR was not significantly correlated with positive p­4E­BP1 and p­S6K1 expression. The survival analyses of the patients with positive p­mTOR, p­4E­BP1, and p­S6K1 tissue samples were not significantly different from those of the patients with negative tissue samples (P>0.05). Thus suggesting that these markers are not adequate risk factors for disease free survival (P>0.05). In conclusion, the results of the present study suggested that p­mTOR, p­4E­BP1, and p­S6K1 are activated in invasive breast cancer. In addition, the exclusive expression of p­4E­BP1 and p­S6K1 in the cytoplasm may be characteristic of progressive breast cancer. However, p­mTOR, p­4E­BP1, and p­S6K1 are not prognostic factors for breast cancer.