Trastuzumab-Induced Severe Thrombocytopenia:A Case Report and Literature Review.

We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×109/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.

Use of Acellular Dermal Matrices in One-stage Implant-based Breast Reconstruction.

Implant-based breast reconstruction is the most common choice in breast cancer patients. Recently,the acellular dermal matrix (ADM) technique has been widely used in implant-based breast reconstruction in the western countries. This article briefly reviews the biological characteristics,history,types,surgical techniques,and postoperative complications of ADM.

Geomorphic processes of a dammed palaeo-lake in the middle Yarlung Tsangpo River, Tibet.

The failure of a natural dam is an extreme geological event. Palaeo-lake sediments were discovered in the broad Xigazê valley and Dazhuka-Yueju gorge in the middle reach of the Yarlung Tsangpo River in Tibet. However, the sedimentary processes, dam failure, and peak flood of the Xigazê dammed palaeo-lake are poorly understood. Hence, we conducted a field survey of eight lacustrine sedimentary terraces in the area. We divided the sedimentary processes of the palaeo-lake into five stages and deposit types: pre-palaeo-lake sediments (fluvial or aeolian deposits); early stage sediments of the palaeo-lake (coarse sand); main stage palaeo-lake sediments (clayey silt and sand), sediments following the discharge of the palaeo-lake (sand and gravel-cobbles); and cover deposits (aeolian sediments and colluvium). Additionally, the water level along the palaeo-lake was almost constant (3811 m a.s.l.). The dam was likely located at the eastern end of the Dazhuka-Yueju gorge. Based on the water level, dam location and 30-m ASTER GDEM2 data, the capacity of the palaeo-lake was estimated as 22.55 km3. To separate the water volume and sediment volume, the sediment surface elevation along the palaeo-lake was simulated based on the elevations of the six lacustrine sedimentary terraces. The volume of the sediment was ~11.56 km3, which was calculated from the dam location, sediment surface elevation, and the ASTER GDEM2 data. Finally, subtraction of the sediment volume from the capacity of the palaeo-lake gave a backwater volume of 10.99 km3. The peak flood possibly exceeded 3.4 × 105 m3/s as a moraine dam joined the discharge during the dam failure. However, the dammed event probably had a limited effect on the landforms at downstream because of the presence of another dammed palaeo-lake in the broad Zetang valley; moreover, the bedrock upstream of the dam was protected from erosion.

[Contrast study on natural radioactive nuclides contents of rice between Xiangshan uranium deposit area, Jiangxi and non-uranium depsoit area].

The contents of natural radioactive nuclides such as uranium and thorium in paddies were analyzed and compared by means of ICP-MS. Totally 14 paddy samples were distinguished into two groups and collected from two rice planting area. One group (12 paddy samples) was collected from the Xiangshan uranium deposit area, Jiangxi province; while the other group (2 samples) collected from non-uranium deposit suburban area of Fuzhou city, Jiangxi, as comparison samples. The distance between the two sampling areas is about 80 kilometers. Before analysis, those paddy samples were continuously carbonized by two hours first, then continuously incinerated for 8 hours at the temperature of 600 degrees centigrade. The results show that the uranium contents in the paddy ash of samples gotten from Xiangshan uranium deposit area range from 0.053 to 1.482 microg x g(-1). The uranium contents of two comparison paddy samples ash are 0.059 and 0.061 microg x g(-1), respectiovely. The average uranium content of paddy ash of uranium deposit area is 0.323 microg x g(-1). Compared with the comparison samples, the uranium contents of paddy ash of uranium deposit area are considerably high, 5.30 times that of non-uranium deposit area. The thorium contents in paddy ash of the uranium deposit area, however, are relatively low and less than that of samples collected from non-uranium deposit area, which range from 0.029 to 0.311 microg x g(-1); The average level is 0.104 microg x g(-1), only about 50% of that of paddy ash sampled from non-urnaium deposit area. Moreover, there is significant linearity correlation between uranium and thorium contents of paddy sampled from Xiangshan uranium deposit area. The positive effects show that the thorium contents of paddy increase as uranium contents of paddy in uranium deposit area increase. The causes for the remarkable difference in uranium contents in paddy between urianium deposit area and non-uranium deposit area are not clear yet. The research on this topic, however, is very important and significant to the regional rice quality and food security.

The Combining Effects of Cell-Free Circulating Tumor DNA of Breast Tumor to the Noninvasive Prenatal Testing Results: A Simulating Investigation.

Massively parallel sequencing of circulating fetal DNA in the plasma of pregnant women is a common method for noninvasive prenatal testing (NIPT) of fetal trisomy 13, 18, and 21. However, circulating DNA is not restricted to pregnant women, with increased levels of plasma DNA also frequently detected in the plasma of cancer patients. Among pregnant women whose NIPT results were inconsistent with the fetal karyotype, a small number of patients have subsequently been diagnosed with a previously undetected malignancy. However, the extent to which circulating tumor DNA (ctDNA) affects the results of NIPT is still unclear. We examined serum from 50 nonpregnant women with breast tumors by NIPT. These samples were then added to serum containing trisomy 13, 18, and 21 fetal DNA to figure out the extent to which maternal tumors can interrupt NIPT results in pregnant women with breast tumors. Concentrations of cell-free DNA (cfDNA) were higher in both pregnant women and breast tumor patients, relative to nonpregnant healthy controls. Among the 50 samples evaluated, 3 produced false positive NIPT results for trisomy 13, 18, or 21, indicating that genomic copy number variations (CNVs) had occurred. Simulation testing also showed that ctDNA can increase the standard deviation of the associated z-scores, which lower absolute z-scores by decreasing the proportion of circulating fetal DNA relative to total DNA. Of the 50 samples tested, 9 fell within the equivocal range and 8 produced false negative results for trisomy 13, 18, or 21. Data presented here show for the first time that ctDNA is able to affect NIPT results in two ways. First, ctDNA can lead to false positive results due to the detection of genomic CNVs in tumor DNA. Alternatively, ctDNA can increase the likelihood of a false negative by decreasing the proportion of circulating fetal DNA in serum.

[Effects of soil on the concentration of rare earth in Nanfeng orange].

Nanfeng orange is a famous fruit in the world, but the content of rare earth in the fruit and its relation to the content in soil were little studied. The present paper studied the contents of rare earth in Nanfeng orange fruit and the effects of soil planting Nanfeng orange on the contents of rare earth in Nanfeng orange fruit by ICP-MS/ICP-AES in order to find the relation of rare earth content in the soil to that in Nanfeng orange fruit. The results showed that ten kinds of rare earths were detected, namely La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Ho and Yb, whose contents range from 0.63 to 0.01 ng x g(-1), while the contents of the ten elements range from 29.36 to 0.07 microg x g(-1) in the soil All data showed that the content of rare earth in fruits is right relative to that in soil. So the authors can conclude that fertilizing with rare earth should be the best way to enhance the content of rare earth in Nanfeng orange fruits.

Neoadjuvant Bevacizumab plus Chemotherapy versus Chemotherapy Alone to Treat Non-Metastatic Breast Cancer: A Meta-Analysis of Randomised Controlled Trials.

PURPOSE: Results from previous randomised controlled trials (RCTs) investigating whether the addition of bevacizumab to neoadjuvant chemotherapy (NAC) could statistically significantly increase the pathological complete response (pCR) and to identify which subgroup would benefit most from such regimens have produced conflicting results. This meta-analysis was designed to assess the efficacy and safety of bevacizumab plus chemotherapy compared with chemotherapy alone in the neoadjuvant setting. METHODS: A literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane library was performed to identify eligible studies. The primary endpoint of interest was pCR. The secondary endpoints were clinical complete rate (cCR), surgery rate, breast-conserving surgery (BCS) rate, and toxicity. The meta-analysis was performed using Review Manager software version 5.3. RESULTS: Nine RCTs matched the selection criteria, yielding a total of 4967 patients (bevacizumab plus chemotherapy: 50.1%, chemotherapy alone: 49.9%). The results of this meta-analysis demonstrated that the addition of bevacizumab to NAC significantly increased the pCR rate (odds ratio [OR] = 1.34 [1.18-1.54]; P < 0.0001) compared with chemotherapy alone. Subgroup analysis showed that the effect of bevacizumab was more pronounced in patients with HER2-negative cancer (OR = 1.34 [1.17-1.54]; P < 0.0001) compared with HER2-positive cancer (OR = 1.69 [0.90-3.20]; P = 0.11). Similarly, in patients with HER2-negative cancer, the effect of bevacizumab was also more pronounced in patients with HR-negative cancer (OR = 1.38 [1.09-1.74]; P = 0.007) compared with HR-positive cancer (OR = 1.36 [0.78-2.35]; P = 0.27). No significant differences were observed between the groups with respect to cCR, surgery rate, or BCS rate. Additionally bevacizumab was associated with a higher incidence of neutropenia, febrile neutropenia, and hand-foot syndrome. CONCLUSIONS: Higher proportions of patients achieved pCR when bevacizumab was added to NAC compared with when they received chemotherapy alone; acceptable toxicities were also found. Subgroup analysis demonstrated that patients with histologically confirmed HER2-negative and HR-negative breast cancer benefited the most.

Breast cancer association studies in a Han Chinese population using 10 European-ancestry-associated breast cancer susceptibility SNPs.

BACKGROUND: Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. METHODS: Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. RESULTS: Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. CONCLUSION: In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.

Mutational analysis of key EGFR pathway genes in Chinese breast cancer patients.

BACKGROUND: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. METHODS: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. RESULTS: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.5%) in the KRAS gene (rs121913530, rs112445441), and nine (7.5%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.3%) of the 22 genotyping assays caused mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. CONCLUSIONS: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

[Value of cardiac troponin I measurement in prediction of anthracycline-induced cardiotoxicity in breast cancer patients].

OBJECTIVE: To evaluate the value of cardiac troponin I (CTnI) measurement in predicting anthracycline-induced cardiotoxicity in patients with breast cancer. METHODS: This study was conducted among 186 breast cancer patients receiving anthracycline-based chemotherapy. Serum cTnI concentrations before and after each cycle of the chemotherapy and the left ventricular ejection fraction (LVEF) before and at the 2nd, 4th and 6th months of the treatment were recorded. According to serum cTnI concentration, the patients were divided into CTnI+ group (with serum CTnI concentration of no less than 0.1 ng/ml, n=60) and CTnI- (<0.1 ng/ml) group (n=126). RESULTS: No patients in this series experienced cardiac heart failure (CHF). The number of patients with a LVEF reduction by over 10% from the baseline was 16 (26.7%) in CTnI+ group, as compared to 7 (5.6%) in CTnI- group, showing a significant difference between the two groups (P<0.01). CONCLUSION: CTnI can be a useful marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer.

[Relationship between D2-40-labeled lymphatic vessel invasion and lymph node metastasis of breast cancer].

OBJECTIVE: To investigate the feasibility of D2-40 labeling for detecting lymphatic vessels in breast cancer tissues and the clinicopathological implications of lymphatic vessel invasion (LVI). METHODS: Immunohistochemistry was used to detect the expression of D2-40 and lymphatic invasion in 72 cases of breast cancer and 15 benign breast tumor tissues, and their correlations to the clinicopathological factors were analyzed. RESULTS: The positivity rate of LVI was 69.4% in breast cancer tissue. In patients with lymph node metastasis, the positivity rate of LVI was significantly higher than that in patients without lymph node involvement (85.7% vs 54.1%, P<0.01), and LVI was found to be positively correlated to axillary lymph node metastasis (r=0.382). CONCLUSION: D2-40 can specially and reliably mark the lymphatic vessels in breast cancer tissues. LVI is positively correlated to axillary lymph node metastasis and occurs earlier than the latter, therefore should be included in routine clinicopathological testing.

[Expressions of D2-40 and CD34 in invasive ductal carcinoma of the breast and the clinical implications].

OBJECTIVE: To investigate the expression of D2-40 and CD34 in invasive ductal carcinoma of the breast and the clinical significance. METHODS: D2-40 and CD34 expressions were detected immunohistochemically in 108 cases of invasive ductal carcinoma of the breast and 30 cases of breast fibroadenoma. The lymphatic microvessel density (LMD) and the microvessel density (MD), marked by D2-40 and CD34, respectively, were calculated and their relationship with the clinicopathological factors was analyzed. RESULTS: The LMD and MD for invasive ductal carcinoma of the breast were significantly higher than those of breast fibroadenoma (P<0.01). One-way ANOVA indicated that the LMD differed significantly between tumors of different histological grades, status of lymph node metastasis and TNM stages; the MD also varied significantly with the tumor size, histological grade, lymph node metastasis and TNM stage. The LMD and MD showed a positive correlation to the tumor size (r=0.335, 0.337), histological grade (r=0.580, 0.671), lymph node metastasis (r=0.690, 0.721) and TNM stage (r=0.623, 0.634), but not to ER, PR or Her-2 status (P>0.05). CONCLUSIONS: D2-40 can specifically mark the lymphatic endothelial cells in invasive ductal carcinoma of the breast. The LMD and MD are positively correlated to the clinicopathological factors of the malignancy. D2-40 and CD34 has the potential for use as the predictors to evaluate the tumor progression and metastasis.

[Value of ultrasonographic grading with high-frequency probes in distinguishing breast tumors].

OBJECTIVE: To investigate the value of ultrasonographic grading with high-frequency probes in differentiating benign and malignant breast tumors. METHODS: Sixty-four women (mean age 44.5-/+13.7 years) with 79 breast tumors underwent high-frequency ultrasonography to examine the tumor number, size, aspect ratio, shape, boundaries, encapsulation, pseudopod, internal and rear echoes, calcifications, blood perfusion, abnormality lymph nodes in the axilla. The tumors were graded based on these findings using a 10-point grading system. RESULTS: Between the 46 women with benign tumors and 18 with malignant tumors, no significant differences were found in the mean tumor number (1.5-/+1.3 vs 1.1-/+0.3, P>0.05) or size (55.0-/+19.2 mm vs 19.8-/+8.3 mm, P>0.05), but the mean age (41.4-/+12.4 years vs 52.4-/+14.1 years) and ultrasonographic grade (2.8-/+2.2 vs 7.3-/+1.7, P<0.05) differed significantly. The ultrasonographic grade of the breast tumors showed an obvious correlation to the nature of the tumors (r=0.695, P<0.001). CONCLUSION: Grading of breast tumors with high-frequency ultrasonography helps evaluate the nature of the tumors, and a higher score suggests increased probability of malignancy.