Clinical Application of BI-RADS（5th Ed）Mammography Lexicon in the Category of Suspicious Calcification / 中山大学学报(医学科学版)

@#Objective】 To explore the clinical application of the fifth edition of BI- RADS for the category of suspicious calcification. 【Methods】 Mammograms of patients with suspicious calcification from May 2012 to May 2017 were reviewed retrospectively. The morphology（amorphous，coarse heterogeneous，fine pleomorphic，fine linear or fine linear branching）and distribution（diffuse，regional，grouped，linear，segmental）of suspected calcification according to the fifth edition of the BI- RADS were analyzed. Taking pathology as the gold standard，the positive predictive value（PPV）of morphology，distribution and combination of morphology and distribution was calculated and compared with the PPV range of the fifth edition of BI- RADS. 【Results】 A total of 170 patients were included in the study，116 were benign，54 were malignant，and PPV was 31.8%（54/170）. In terms of morphology，amorphous，coarse heterogeneous， fine pleomorphic calcification were category 4B（10%

Interaction of body mass index and a polymorphism in gene of catalytic subunit of glutamate cysteine ligase on breast cancer risk among Chinese women / 中华流行病学杂志

Objective To investigate the interaction of body mass index (BMI) and a single nucleotide polymorphism (SNP,rs17883901) in catalytic subunit of glutamate-cysteine ligase (GCLC) on breast cancer risk.Methods A total of 839 women with incident breast cancer and 863 age-matched controls without cancer were recruited at the same period in three affiliated hospitals of Sun Yat-sen University in Guangzhou from October 2008 to June 2010.GCLC rs17883901 was genotyped by MALDI-TOF-MS.Binary unconditional logistic regression was applied to calculate odds ratios and 95％ confidence intervals.Results The difference of present BMI and BMI at age 20 was not statistically significant between cases and controls,either as the genotypes of GCLC.No association was found between BMI at present and premenopausal or postmenopausal breast cancer risk.But we found that women who had a BMI at age 20 of 18.5 to 22.9 had a marginally decreased risk of premenopausal breast cancer [OR and 95％CI:0.69 (0.48,1.00)].Among women with CT/TT genotypes,whose present BMI was greater than 25 had a increased risk [OR and 95％CI:1.91 (1.09,3.36)] of breast cancer and a decreased risk [OR and 95％CI:0.56(0.31,0.99)] with a BMI at age 20 of 18.5 to 22.9.There was a interaction between GCLC gene (rs17883901)and BMI at present in breast cancer risk (P=0.043),which was not found between rs17883901 and BMI at age 20.Conclusion Our findings indicate BMI at age 20 may be a protective factor of premenopausal breast cancer,while no association appears between GCLC (rs17883901) and breast cancer.Obesity at present may significantly increase the risk of breast cancer among women with CT/TT genotypes of GCLC (rs17883901).

Association between urinary cadmium and clinicopathological characteristics of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the association between urinary cadmium and clinicopathological characteristics of breast cancer.</p><p><b>METHODS</b>The clinicopathological characteristics of 240 patients with breast cancer were obtained and urine specimens were collected from October 2009 to July 2010. The concentration of urinary cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). χ(2) test and Wilcoxon rank sum test were used to analyze whether urinary cadmium is associated with clinicopathological characteristics of breast cancer.</p><p><b>RESULTS</b>The median concentration of urine cadmium of 240 patients was 1.99 µg/g (25th percentile, 1.32 µg/g; 75th percentile, 2.88 µg/g). HER-2 positive rate, regional/distant metastasis rate, and advanced stage rate in patients with the highest tertile of cadmium concentration were significantly higher than those in the patients with second and lowest Cd tertiles (P = 0.042, P = 0.028 and P = 0.017, respectively), and 28.2% vs. 16.5% for HER-2 and 47.2% vs. 32.0% for regional/distant metastasis, respectively. There were still significant associations between urinary cadmium levels and these clinicopathological parameters after being adjusted in age by unconditional logistic regression model, respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>The results of this study suggest that urinary cadmium levels are associated with the HER-2 status, regional/distant metastasis status and stages of breast cancer, respectively. Cadmium may induce highly aggressive breast cancer in humans.</p>

Ubc9 expression predicts chemoresistance in breast cancer / 癌症

Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in tumorigenesis. Whether Ubc9 is involved in the chemoresistance of breast cancer remains unknown. In this study, we aimed to evaluate the contribution of Ubc9 in the chemoresistance of breast cancer. Immunohistochemistry (IHC) was used to examine the expression level of Ubc9. Chi-square test, Wilcoxon test, and one-way ANOVA were applied to analyze the relationship between Ubc9 expression, clinicopathologic features, and clinical response to neoadjuvant chemotherapy. The significance of variables for survival was analyzed by the Cox proportional hazards model in a multivariate analysis. Kaplan-Meier survival curves were plotted and log-rank test was performed. The proportion of Ubc9-positive cells was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 ± 17.94)% vs. (5.82 ± 2.80)%, P < 0.001]. High Ubc9 expression was associated with poor differentiation (Χ² = 6.538, P = 0.038), larger tumor size (Χ² = 4.701, P = 0.030), advanced clinical stage (Χ² = 4.651, P = 0.031), lymph node metastasis (Χ² = 9.913, P = 0.010), basal-like phenotype (Χ² = 8.660, P = 0.034), and poor clinical response to neoadjuvant chemotherapy (Χ² = 11.09, P = 0.001). The expected 6-year cumulative disease-free survival rate was 87.32% in patients with low Ubc9 expression compared to 68.78% in those with high Ubc9 expression (Χ² = 4.289, P = 0.038). These data indicate that high Ubc9 expression correlates with poor response to chemotherapy and poor clinical prognosis.

Analysis of BRCA1 gene mutations in patients with early-onset breast cancer and their affected relatives in Guangdong province / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the BRCA1 mutations in patients with early-onset breast cancer and their affected relatives in Guangdong province and explore the relationship between BRCA1 mutation and the expressions of estrogen receptor(ER), progesterone receptor(PR), HER2 and ALN.</p><p><b>METHODS</b>From 58 patients with early-onset breast cancer and their affected relatives, the genomic DNA was extracted from the peripheral blood mononuclear cells and the coding regions of the BRCA1 gene was amplified using polymerase chain reaction. BRCA1 gene mutations were screened by denaturing high performance liquid chromatography (DHPLC) and subsequent direct DNA sequencing. The expression of ER, PR, HER2 and ALN were detected with immunohistochemistry and their relations with the gene mutation were analyzed.</p><p><b>RESULTS</b>Disease-related BRCA1 mutations were detected in 2 of the 58 patients, who were younger than 35 years old, including 1 with a novel splice-site mutation (IVS5-1 G-->A). No association was found between this novel mutation and the expressions of ER, PR, HER2 and ALN.</p><p><b>CONCLUSION</b>The incidence of BRCA1 mutation is significantly lower in patients with early-onset breast cancer and their affected relatives in Guangdong province than in the Western populations. The novel mutation identified in BRCA1 gene may represent a mutation characteristic of the patients in Guangdong province. BRCA1 gene mutations may not have any relation with the expression of ER, PR, HER2 and ALN.</p>

Phase II study of docetaxel plus epirubicin versus docetaxel plus cisplatin as first-line chemotherapy for advanced breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of combination of docetaxel plus epirubicin (TE) versus docetaxel plus cisplatin (TP) as first-line chemotherapy for locally advanced or metastatic breast cancer.</p><p><b>METHODS</b>Eighty-eight patients were randomized into two groups with a ratio of 2:1, either to receive TE or TP regimen. The patients received docetaxel 75 mg/m2 plus epirubicin 60 mg/m2 (TE group) or docetaxel 75 mg/m2 plus cisplatin 75 mg/m2 (TP group) administrated intravenously. Both regimens were once repeated 3 weeks later. The efficacy, time to progression and safety were evaluated at the end of the second cycle.</p><p><b>RESULTS</b>Complete response was achieved in 5% of TE group and 3.6% of TP. Overall (complete plus partial) response rates in TE and TP group were 48.3% and 60.7%, respectively (P = 0.2788). Disease control rates (CR + PR + SD) for TE and TP groups were 83.6% and 80%, respectively (P = 0.4899). The median time to progression (TTP) was 10 months for TE versus 8 months for TP groups (P = 0.7119). The major grade III or IV toxicities were neutropenia (66.7% in TE; 53.6% in TP, P = 0.2373); and alopecia (30.0% in TE; 10.7% in TP, P = 0.0508).</p><p><b>CONCLUSION</b>Both TE and TP regimens as first-line chemotherapy were similarly effective, safe and tolerable in the treatment for locally advanced or metastatic breast cancer.</p>

Alternatively activated macrophages/mononuclear phagocytes promote growth and invasion of breast cancer cell line SKBR3 / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of alternatively activated macrophages /mononuclear phagocytes(MNP) on breast cancer cells and explore the mechanisms for the action of tumor-associated macrophages in breast cancer.</p><p><b>METHODS</b>Human peripheral blood monocytes were isolated and cultured in vitro and divided into 3 groups, namely classically activated monocytes (CAM) which were induced by lipopolysaccharide, alternatively activated monocytes (AAM) induce by IL-4, and control cells treated with the culture medium only. After cell culture for 48-72 h, the mRNA of tumor necrosis factor-alpha (TNF-alpha), alternative monocytes activation- associated CC-chemokine 1 (AMAC-1), and beta-actin of the 3 groups were extracted for RT-PCR, or the cells were cocultured with breast cancer cell line SKBR3, or seeded in chicken chorioallantoic membrane along with SKBR3.</p><p><b>RESULTS</b>TNF-alpha mRNA was significantly increased in CAM, and AMAC-1 was highly expressed in AAM. The coculture experiments showed that CAM exhibited obvious inhibitory effect on SKBR3 cells after a 3-day culture whereas AAM significantly promoted the growth of SKBR3 cells after a 5-day culture. In chicken on chorioallantoic membrane experiment, the macrophages promoted tumor angiogenesis and AAM showed the most obvious effect.</p><p><b>CONCLUSION</b>IL-4 induces high expression of AMAC-1, a molecular marker of AAM, in the macrophages, and AAM can promote the growth of SKBR3 cells and tumor angiogenesis.</p>

Vector-mediated HER-2 RNA interference against HER-2-positive breast cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the feasibility of vector-mediated RNA interference for HER-2-positive breast cancer therapy.</p><p><b>METHODS</b>A plasmid vector capable of mediating HER-2 RNA interference was constructed, and HER-2-positive breast cancer cell line SKBR-3 was transfected with this constructed vector. The expression of HER-2 mRNA and protein was analyzed by RT-PCR and Western blotting, and the growth and apoptosis of SKBR-3 cells was analyzed after transfection.</p><p><b>RESULTS</b>The expressions of HER-2 mRNA and HER-2 protein was downregulated in response to vector-mediated HER-2 RNA interference, which also resulted in tumor cell growth inhibition and increased number apoptotic cells.</p><p><b>CONCLUSION</b>HER-2 is a good target for RNA interference and RNA interference targeting HER-2 can lead to HER-2 breast cancer cell apoptosis and growth inhibition.</p>

Neoadjuvant chemotherapy with docetaxel plus epirubicin for locally advanced breast cancer: a multi-center phase II study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical response, pathological complete response (pCR), tumor resection rate and safety of neoadjuvant chemotherapy with docetaxel and epirubicin (ET) for locally advanced breast cancer (LABC).</p><p><b>METHODS</b>From March to December 2001, 40 women with LABC, aged from 28-67 (medium 48) years were alloted. Twenty patients had clinical stage IIIa disease, 15 had stage IIIb disease and 5 stage IV patients who had ipsilateral sura-clavicular metastasis. The dose was: epirubicin (E) 60 mg/m2, docetaxel (T) 75 mg/m2 every 3 weeks, with G-CSF given preventively. After 2 cycles of ET, a pilot clinical response evaluation was performed by investigators for each patient to decide if she should receive another 1-2 cycles of ET before surgery or radiation therapy.</p><p><b>RESULTS</b>Thirty-eight patients received 2-3 cycles of ET regimen. The pCR, clinical complete response (cCR) and clinical partial response (cPR) rates were 15.0%, 20.0% and 52.5%, respectively. Tumor resection rate in this group was 92.5%. Incidence of III/IV Grade neutropenia was 8.4%/14.0% of cycles, and 3 patients suffered from neutropenia with fever. Non-hematological adverse events were alopecia, nausea, vomiting, fluid retention, myalgia, arthralgia and nail disorders, which were mild to moderate.</p><p><b>CONCLUSION</b>Neo-adjuvant chemotherapy with a combination of docetaxel and epirubicin is effective and well tolerated by women with locally advanced breast cancer.</p>