Background: In women with duct carcinoma in-situ (DCIS) receiving breast conservation therapy (BCT), in-breast recurrences are seen in approximately 10%, but cannot be accurately predicted using clinical and histological criteria. We performed a case-control study to identify protein markers of local recurrence risk in DCIS.
Recannulation and lavage of the same duct after a 6 month interval can be achieved with high frequency; however, reproducibility of cell yield and cytologic findings from the same duct is sub-optimal, leading to significant attrition of evaluable subjects. The utility of DL for the serial monitoring of breast epithelium is therefore limited.
Effective methods of serial epithelial sampling to measure breast-specific biomarkers will aid the rapid evaluation of new preventive interventions. We report here a proofof-principle phase 2 study to assess the utility of ductal lavage (DL) to measure biomarkers of tamoxifen action. We enrolled women with a 5-year breast cancer risk estimate >1.6% or the unaffected breast of women with T 1a or T 1b breast cancer. After entry DL, participants chose tamoxifen or observation and underwent repeat DL 6 months later. Samples were processed for cytology and immunohistochemistry for estrogen receptor α, Ki-67, and cyclooxygenase-2. Of 182 women recruited, 115 (63%) underwent entry and repeat DL; 85 (47%) had sufficient cells for analysis from ≥1 duct at both time points; in 78 (43%), cells were sufficient from ≥1 matched ducts. Forty-six women chose observation and 39 chose tamoxifen. We observed greater reductions in the tamoxifen group than in the observation group for Ki-67 (adjusted P = 0.03) and estrogen receptor α (adjusted P = 0.07), but not in cyclooxygenase-2 (adjusted P = 0.4) labeling. Cytologic findings showed a trend toward improvement in the tamoxifen group compared with the observation group. Interobserver variability for cytologic diagnosis between two observers showed good agreement (κ = 0.44). Using DL, we observed the expected changes in tamoxifen-related biomarkers; however, poor reproducibility of biomarkers in the observation group, the 53% attrition rate of subjects from recruitment to biomarker analyses, and the expense of DL are significant barriers to the use of this procedure for biomarker assessment over time.Ductal lavage (DL) is a minimally invasive technique that allows sampling of breast ductal epithelium in healthy high-risk women with a significantly better cell yield compared with nipple aspirate fluid (1-3). This allows the possibility of monitoring response to prevention agents by serial sampling of epithelial cells, using biomarkers relevant to the agent being tested. Thus, DL is a potentially attractive tool for assessing the effects of chemoprevention agents (1).To establish the principle that biomarkers of chemoprevention agents can be monitored using DL, we initiated a phase 2, nonrandomized trial using tamoxifen, the gold-standard breast cancer chemoprevention agent (4). We reasoned that the efficacy of tamoxifen in the prevention of estrogen receptor (ER)-positive breast cancer has been clearly shown and a study using tamoxifen as the preventive intervention should enable the efficient evaluation of DL as a tool for repeat epithelial sampling in phase 2 prevention studies. Furthermore, because tamoxifen does not prevent all breast cancer cases, if markers of tamoxifen efficacy could be identified it may be possible to target therapy to those most likely to benefit from it.We now report the final results of this trial, having recruited 182 women, of whom 85 were evaluated for biomarker results at two time points. We present a comparative analysis of women who accepted ...
BackgroundBSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP). BSEP disease is associated with an increased risk of hepatobiliary cancer.Case PresentationA 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat.ConclusionsClinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.
Document clustering is an integral and important part of text mining. There are two types of clustering, namely, hard clustering and soft clustering. In case of hard clustering, data item belongs to only one cluster whereas in soft clustering, data point may fall into more than one cluster. Thus, soft clustering leads to fuzzy clustering wherein each data point is associated with a membership function that expresses the degree to which individual data points belong to the cluster. Accuracy is desired in information retrieval, which can be achieved by fuzzy clustering. In the work presented here, a fuzzy approach for text classification is used to classify the documents into appropriate clusters using Fuzzy C Means (FCM) clustering algorithm. Enron email dataset is used for experimental purpose. Using FCM clustering algorithm, emails are classified into different clusters. The results obtained are compared with the output produced by k means clustering algorithm. The comparative study showed that the fuzzy clusters are more appropriate than hard clusters.
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