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Tumor levels of the cell cycle regulators cyclin E and p27 correlate strongly with survival in breast cancer patients and are specifically regulated by the ubiquitin ligases hCDC4 and SKP2. This study was to explore whether genetic susceptibility to breast cancer is associated with polymorphism of these genes and whether gene-gene and gene-risk factor [i.e. full-term pregnancy (FTP)] interactions are important in determining cancer risk. A two-stage case-control study based on single-nucleotide polymorphisms was performed. The first study (560 cases and 1122 controls) was to define the contribution of cell cycle and ubiquitin ligase genes to cancer susceptibility. The second study (926 cases and 923 controls) was to confirm the association identified in the first stage and to map the variant alleles. Increased breast cancer risk was associated with both polymorphism of hCDC4 and a joint effect of cyclin E and hCDC4. These associations were more significant in nulliparous women, and cancer risk associated with a lower number of FTPs was only seen in women with a higher number of high-risk genotypes, providing support for an effect of gene-risk factor interaction in determining susceptibility. Sequence variants of intron 2 in hCDC4 were found to be the most significant polymorphism and high-stage estrogen receptor (ER)-negative patients carrying the homozygous variant genotype manifested significantly poorer survival. This study concludes that polymorphism of hCDC4 is a risk factor for breast cancer development by interacting with either cyclin E or FTP and may also prove useful in predicting progression of patients with high-stage and ER-negative breast cancers.

Background: The common practice for diagnosis of complex cystic breast masses (CCBM) may be imaging-guided aspiration or biopsy of cystic or solid components., Purpose: To assess the diagnostic value of sonographically guided needle sampling of cystic and solid components for CCBM., Material and Methods: Twenty patients with 20 CCBM underwent sonographically guided fine-needle aspiration biopsy (FNAB) for cystic components, followed by core needle biopsy (CNB) for residual solid components. The diagnostic results of each were evaluated. Excisional biopsy or mastectomy served as a reference standard., Results: Fourteen (70%) masses were malignant. Needle sampling for cystic components of the 14 malignant tumors showed malignancy in one (7%), atypia in four (29%), benign findings in four (29%), and insufficient samples in five (36%). Needle sampling for residual solid components showed malignancy in 11 (79%), atypia in two (14%), and insufficient sample in one (7%). The diagnostic yield of needle sampling of solid components was significantly higher than that of cystic components for malignant CCBM (P<0.05). Sixteen (80%) of 20 CCBMs showed bloody fine-needle aspirates. There was no significant difference between the rates of bloody aspirates of malignant and benign CCBM (86% vs. 67%, P=0.55)., Conclusion: Sonographically guided needle sampling of solid components may help to identify most malignant CCBMs, and the aspirated fluid may be discarded due to low diagnostic value.

Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.

Much attention is currently focused on one of the newest breast examination techniques, breast MRI. Contrast-enhanced breast MRIs acquired by contrast injection have been shown to be very sensitive in the detection of breast cancer, but are also time-consuming and cause waste of medical resources. This paper therefore proposes the use of spectral signature detection technology, the Kalman filter-based linear mixing method (KFLM), which can successfully present the results as high-contrast images and classify breast MRIs into major tissues from four bands of breast MRIs. A series of experiments using phantom and real MRIs was conducted and the results compared with those of the commonly used c-means (CM) method and dynamic contrast-enhanced (DCE) breast MRIs for performance evaluation. After comparison with the CM algorithm and DCE breast MRIs, the experimental results showed that the high-contrast images generated by the spectral signature detection technology, the KFLM, were of superior quality.

The present case-control study was to investigate the relationships of plasma leptin level and anthropometric measures of adiposity with the risk of breast cancer. Questionnaire information, anthropometric measures and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei, between 2004 and 2006. Plasma levels of leptin were measured by RIA. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the associations. Overall, higher leptin concentrations were significantly associated with an increased risk of breast cancer (OR (95% CI) for top vs bottom tertile of leptin was 1.63 (1.07-2.49), P(trend)=0.009). Waist circumference was a significant anthropometric factor for breast cancer in both pre- and postmenopausal women. Furthermore, the associations of leptin with breast cancer risk remained after adjustment for obesity indices. These results suggest that leptin may have an independent role in breast tumorigenesis. Regardless of the impact of circulating leptin, more research is needed to elucidate molecular mechanisms and local leptin levels that are critical for the development of breast cancers.

The role of the familial breast cancer susceptibility genes, BRCA1 and BRCA2, in the homologous recombination (HR) pathway for DNA double-strand break (DSB) repair suggests that the mechanisms involved in HR and DNA DSB repair are of etiological importance during breast tumorigenesis. Bloom (BLM) helicase directly interacts with RAD51 recombinase, which is involved in regulating HR, and it is thus of particular interest to examine whether this interaction is associated with breast cancer susceptibility. This single-nucleotide polymorphism (SNP)-based case-control study was performed to examine this hypothesis using specimens from 933 patients with breast cancer and 1539 healthy controls. The results showed that one SNP (rs2380165) in BLM and two (rs2412546 and rs4417527) in RAD51 were associated with breast cancer risk. Furthermore, haplotype and diplotype analyses based on combinations of five SNPs in RAD51 revealed a strong association between RAD51 polymorphisms and breast cancer risk (P < 0.05). Support for the interaction between BLM and RAD51 in determining breast cancer risk came from the finding that the association between cancer risk and at-risk genotypes/haplotype pairs of RAD51 was stronger and more significant in women harboring homozygous variant alleles of BLM (P for interaction < 0.05). Interestingly, not only the intronic SNP located within the region encoding the helicase domain of BLM but also those within the RAD51-interaction domain-encoding region showed an interaction with RAD51 polymorphisms in determining breast cancer susceptibility. Our results suggest a contribution of BLM and RAD51 to breast cancer development and provide support for the tumorigenic significance of the functional interaction between these two HR proteins.

Polyacrylamide hydrogel (PAAG) was widely used for injection augmentation mammoplasty in Eastern Europe and China although uncommon in the western countries. However, the safety of this procedure remained controversial. Herein, we report a 30-year-old woman with a history of augmentation mammoplasty by PAAG injection developed galactoceles during her pregnancy. Ultrasound and magnetic resonance imaging showed huge cystic lesions in bilateral breasts; as a result, the normal breast tissue was almost completely replaced. On the basis of the imaging findings, the patient underwent mastectomy as well as immediate breast reconstruction with satisfactory outcome. It is important to be familiar with the imaging findings of this rare yet severe complication after augmentation mammoplasty in order to make an accurate diagnosis and a proper management.

Background/aims: A retrospective study of Chinese patients with pancreatic pseudocysts to compare the results between non-conservative and conservative treatments, and the use of serial serum amylase and imaging in monitoring treatment success., Methodology: One hundred and sixty-two pseudocyst patients, treated between 1974 and 2003, were divided into two groups, conservative treatment and interventions (percutaneous needle drainage, internal drainage, or resection), and treatment results for these groups compared., Results: Ninety-one cases (56%) showed spontaneous pseudocyst resolution (mean duration to resolution, 33.4 days). Pseudocyst size was less than 5cm in 86 of these cases (94.5%). Excellent symptomatic responses after aggressive treatment were noted in 68 of 71 patients (93.1%) with pseudocysts larger than 5 cm. All percutaneous tube drainage patients had pseudocyst resolution when the pseudocyst size was less than 5 cm. Hyperamylasemia was noted in 114 cases (70.4%) at diagnosis and returned to normal range in those patients whose cysts underwent spontaneous resolution or who had successful operations., Conclusions: Pancreatic pseudocysts smaller than 5 cm should have conservative treatment or percutaneous needle drainage. Larger pseudocysts should be treated aggressively. Serum amylase and ultrasound examinations are important to evaluate the occurrence of spontaneous resolution or the need for surgical intervention.

The evolutionarily conserved Mre11-Rad50-Nbs1 (MRN) complex, consisting of proteins encoded by the genes Mre11, Rad50, and Nbs1, was recently shown to play a crucial role in DNA double-strand break (DSB) repair by recruiting the nuclear protein kinase ataxia telangiectasia mutated to DSB sites, leading to activation of this DNA repair network. Given the fact that carriers of defective mutation and polymorphic variants of ataxia telangiectasia mutated are at higher risk of developing breast cancer, we hypothesized a role of the MRN genes in determining breast cancer susceptibility. This hypothesis was examined both in a case control study of 559 breast cancer patients and 1,125 healthy women of single-nucleotide polymorphisms in Mre11, Rad50, and Nbs1 and by the in vivo detection of binding between Mre11 and BRCA1, encoded by the breast cancer susceptibility gene BRCA1. We were also interested in defining whether any association between MRN genes and breast cancer was modified by reproductive risk factors reflecting the level of estrogen exposure or susceptibility to estrogen exposure, as estrogen is known to initiate breast cancer development due to its metabolites causing DSB formation. Support for the hypothesis came from the observations that (a) one single-nucleotide polymorphism in Nbs1 was significantly associated with breast cancer risk, and a trend toward an increased risk of developing breast cancer was found in women harboring a greater number of putative high-risk genotypes of MRN genes (an adjusted odds ratio of 1.25 for each additional putative high-risk genotype; 95% confidence interval, 1.10-1.44); (b) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to be more susceptible to estrogen, i.e., those with no history of full-term pregnancy, those older (>or=26 years of age) at first full-term pregnancy, or those having had fewer (<2) full-term pregnancies; the risk effect conferred by harboring a higher number of high-risk genotypes of MRN genes was more significant in women without a history of breast feeding; and (c) Mre11 and BRCA1 were shown to form a complex in vivo, and this interaction was increased by irradiation. This study supports the role of the MRN pathway in breast cancer development, further strengthening the suggestion that mechanisms regulating DSB repair may play a mutator role driving breast cancer pathogenesis.

Adiponectin is a peptide hormone secreted exclusively by adipocytes, and obesity is an established risk factor for breast cancer. We have, thus, evaluated the associations of anthropometric measures of adiposity and adiponectin with the development of breast cancer in a case-control study. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 244 incident cases with breast cancer, including 141 premenopausal and 103 postmenopausal cases, and 244 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2005. Plasma levels of adiponectin were measured by RIA. The relationship between anthropometric measures of adiposity and breast cancer risk was modified by menopausal status, with a significant increase in risk observed in postmenopausal but not premenopausal women. Moreover, a fairly robust inverse association of adiponectin with the risk was observed only in postmenopausal women (adjusted odds ratio (OR), 0.55; 95% confidence interval (CI), 0.23-0.97), but not in premenopausal women. Additionally, the plasma adiponectin levels tended to be inversely associated with estrogen receptor (ER)-positive (adjusted OR, 0.53; 95% CI, 0.27-0.98) but not ER-negative breast tumors. Furthermore, the associations of adiponectin with breast cancer risk overall and by menopausal and ER status remained after adjustment for obesity indices. These results suggest that adiponectin may have an independent role in breast carcinogenesis, particularly in the postmenopausal and ER-positive breast cancer risk.

Aneuploidy occurs early during tumorigenesis and may contribute to tumor formation. Tumor cells become aneuploid as a result of aberrant mitotic divisions, suggesting a tumorigenic contribution of the mechanisms in maintaining chromosomal number stability. We therefore speculated that the genes TTK, MAD2L1, BUB1, BUB1B and PTTG1 (Securin), jointly implicated in the regulation of mitotic checkpoint, might be associated with breast tumorigenesis. To test this hypothesis, this case-control study of 698 primary breast cancer patients and 1492 healthy controls examined single-nucleotide polymorphisms (SNPs) in these mitotic checkpoint genes to define their tumorigenic contribution. Because estrogen is known to promote breast cancer development via its mitogenic effect leading to malignant proliferation of breast epithelium and the mitotic checkpoint genes are involved in regulating mitosis, we were also interested in knowing whether any association between genotypes and breast cancer risk was modified by reproductive risk factors. Support for these hypotheses came from the observations that (i) two SNPs in TTK and PTTG1 were associated with breast cancer risk; (ii) haplotype and haplotype combination analyses in TTK, BUB1B and PTTG1 revealed a strong association with breast cancer risk; (iii) a trend to an increased risk of breast cancer was found in women harboring a greater number of putative high-risk genotypes/haplotypes of mitotic checkpoint genes and (iv) a significant interaction between high-risk genotypes/haplotypes and reproductive risk factors in determining breast cancer risk was defined. This study provides new support for the mutator role of mitotic checkpoint genes in breast cancer development, suggesting that breast cancer could be driven by genomic instability associated with variant mitotic checkpoint genes, the tumorigenic contribution of which could be enhanced as a result of increased mitosis due to estrogen exposure.

The high risk of developing cancer seen in human genetic diseases that resemble accelerated aging provides support for a tumorigenic contribution of the mechanisms and genes responsible for regulating life span and aging. We therefore speculated that the WRN gene (encoding RECQL2, a DNA helicase), the germline mutation of which causes the progeroid disorder Werner syndrome, may be associated with breast tumorigenesis. This hypothesis was tested in this case-control study of 935 primary breast cancer patients and 1,545 healthy controls by examining single-nucleotide polymorphisms (SNPs) in WRN. We were also interested in knowing whether any identified association between WRN and breast cancer was modified by reproductive risk factors reflecting susceptibility to estrogen exposure. Our hypothesis is that because estrogen is known to promote breast cancer development via its mitogenic effect leading to cell proliferation, and because WRN is an essential gene, as its suboptimal function leads to a severe decrease in proliferation, estrogen stimulation may have a protective effect on cells harboring variant WRN, allowing them to survive and proliferate for the prolonged period needed for tumor formation. Support for this hypothesis came from the following observations: (a) one SNP in WRN was significantly associated with breast cancer risk (P = 0.002); (b) haplotype and diplotype analyses, based on different combinations of multiple SNPs in WRN, revealed a strong association with breast cancer risk; (c) this association between risk and putative high-risk genotypes was stronger and more significant in women with a longer interval between menarche and first full-term pregnancy; and (d) the protective effect conferred by having a higher number of full-term pregnancy was only significant in women with homozygous or heterozygous wild-type WRN genotypes. This study provides support for the tumorigenic role of WRN in breast cancer development, suggesting that breast cancer can be driven by the aging associated with variant WRN, the tumorigenic contribution of which might be enhanced as a result of increased cell growth due to estrogen exposure.

Background: Sentinel node (SN) biopsy for patients with locally advanced breast cancer after neoadjuvant chemotherapy results in a lower detection rate and higher false-negative rate. The aims of the study were to explore the role of SN biopsy in these patients in Taiwan and to assess the role of intraoperative ultrasound examination of the non-SN level., Methods: We used a blue dye to identify the SNs in 127 patients with T3 locally advanced breast cancer initially treated with neoadjuvant chemotherapy. After SN biopsy, we used intraoperative ultrasound to explore the non-SN region for additional lymph nodes, followed by at least level II axillary dissection. All the SNs were evaluated histologically and immunohistochemically with anticytokeratin antibodies. All the non-SNs were examined by routine histology., Results: SNs were identified in 116 (91.3%) of 127 procedures. SN metastases were found in 64 cases (55.2%). Subsequent axillary dissection revealed tumor involvement of non-SNs in 40 (62.5%) of 64 cases. SN biopsy results had a sensitivity of 92.8%, a specificity of 100%, and a false-negative rate of 9.6%. Furthermore, intraoperative ultrasound detected suspicious malignant nodes in the non-SN level in 39 out of 40 cases, and detected 5 cases with non-SN metastases that had false-negative SN mapping. This technique decreased the false-negative rate of SN mapping from 9.6% to only 1.39% for these cases., Conclusions: SN biopsy results combined with intraoperative ultrasonography can accurately assess the non-SN status and help breast surgeons to decide whether subsequent axillary dissection is warranted after SN biopsy has been performed.

Purpose: To evaluate whether intraoperative ultrasonography can help surgeons to identify patients with breast cancer and metastases confined to the sentinel node., Experimental Design: We used blue dye to identify sentinel node during 512 procedures done on 509 patients with breast cancers of <3 cm. After sentinel node biopsy, we used intraoperative ultrasonography to explore the whole axilla followed by at least level II axillary dissection. All sentinel nodes were evaluated histologically and immunohistochemically using anti-cytokeratin antibody. All nonsentinel nodes were examined by routine histology. Multiple logistic regression was used to assess the associations of interest and to adjust for potential confounders. Receiver operating characteristic curves were used to calculate the areas under the curves of interest and for comparisons., Results: Sentinel nodes were identified in 506 of 512 (98.8%) procedures and sentinel node metastases were found in 161 of these (31.8%). Subsequent axillary dissection revealed tumor involvement in nonsentinel nodes in 93 of 161 (57.8%) procedures. Multivariate analysis showed that tumor size, number of positive sentinel nodes, and metastatic size in sentinel nodes were independent factors predicting the presence of tumor-positive nonsentinel nodes. The validity of using either node size or cortical thickness ascertained by intraoperative ultrasound to predict nonsentinel node metastases was highly significant (P < 0.0001). Intraoperative ultrasound not only detected metastatic nonsentinel nodes in 89 of 93 (95.7%) cases but also detected metastatic nonsentinel nodes in patients with false-negative sentinel node mapping., Conclusion: Sentinel node biopsy combined with intraoperative ultrasonography can help breast surgeons decide whether to perform a subsequent nonsentinel node dissection after identification of a positive sentinel node.

The reproductive hormone, estrogen, contributes to the development of breast cancer by binding to the estrogen receptor (ER) in the nucleus, triggering cell growth and tumor promotion. In addition to its role in regulating target genes and signaling pathways involved in cell cycle progression, the ER-signaling pathway may regulate the expression of chromatin-remodeling gene, Metastasis-associated 3 (MTA3), or interact with chromatin-remodeling protein, Metastasis-associated 1 (MTA1). The invasion-suppressor gene, E-Cadherin (E-Cad), has recently been identified as a downstream target gene regulated by the ER-MTA3 pathway via the transcriptional repressor, Snail, and the ER-MTA3-Snail-E-Cad pathway has therefore been evoked to explain the clinical observation that ER expression in breast cancer is generally associated with a better clinical outcome. Since E-Cad may play an initiating role during breast tumorigenesis, we hypothesized that this ER-signaling pathway may also determine susceptibility to breast cancer, and examined this in a multigenic case-control study of 468 incident breast cancer patients and 470 healthy controls by genotyping the single nucleotide polymorphisms (SNPs) in five genes (ER, MTA3, Snail, E-Cad, and MTA1) in the ER-signaling pathways. Support for this hypothesis came from the observations that (a) with the exception of Snail, which interacted differently with reproductive risk factors in relation to breast cancer risk, there was a joint effect of the SNPs of these genes and estrogen-related risk factors (age at first full-term pregnancy and obesity, measured by the body mass index) on breast cancer risk (p < 0.05); (b) a trend toward increased risk of developing breast cancer was seen in women harboring a greater number of putative high-risk genotypes of these genes in ER-signaling pathways; (c) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to have experienced higher estrogen level, i.e., obese women; and (d) the risk effect conferred by obesity was only significant in women with a higher number of putative high-risk genotypes of the ER-signaling genes. These epidemiological findings highlight the role of newly identified novel ER-related pathways in breast cancer development and provide a more comprehensive picture of the tumorigenic effect of estrogen in breast cancer development.

Background: Few studies have been published regarding the practice of breast cancer screening in Asian countries., Aims: The present study illustrates how the health policy for breast cancer screening has evolved in Taiwan from selective mammographic screening within a high-risk group, firstly to a programme of physical examination by public health nurses, and finally to a two-stage breast cancer screening programme, with a risk assessment followed by mammography for those at moderate to high risk., Data Sources: Breast cancer screening has evolved from 1995 to 2004 in Taiwan in three stages: (1) selective screening for breast cancer with mammography, ultrasound and physical examination only in first-degree relatives of breast cancer cases (1995-1998); (2) a programme of mass screening (1999-2001) with physical examination by public health nurses; and (3) two-stage breast cancer screening with a risk factor questionnaire and mammography for those deemed at moderate-to-high risk (2002-2004). The questionnaire was based on significant risk factors in a previous epidemiological study, in conjunction with the physical examination programme, a risk score was constructed from the logistic regression coefficients from the previous study, and women with a score above the median in the previous epidemiological study were assigned to mammography., Results: Two-stage mammography screening had the most favourable results compared with the two previous screening regimes. It had a positive predictive value of recall after mammography of 14%, compared with 8% for selective screening and 2% for physical examination. Of screen-detected cancers in the two-stage programme, 71% were either ductal carcinoma in situ or stage T1, compared with 61% for selective screening and 60% for physical examination. The area under the receiver operating characteristic curve was 71% for the two-stage programme., Conclusions: For a low- to medium-risk country such as Taiwan, two-stage screening has acceptable parameters of recall and cancer detection, and compares well with other screening strategies.

This paper presents a 3D localization method to register clustered microcalcifications on mammograms from cranio-caudal (CC) and medio-lateral oblique (MLO) views. The method consists of three major components: registration of clustered microcalcifications in CC and MLO views, 3D localization of clustered microcalcifications and 3D visualization of clustered microcalcifications. The registration is performed based on three features, gradient, energy and local entropy codes that are independent of spatial locations of microcalcifications in two different views and are prioritized by discriminability in a binary decision tree. The 3D localization is determined by a sequence of coordinate corrections of calcified pixels using the breast nipple as a controlling point. Finally, the 3D visualization implements a virtual reality modeling language viewer (VRMLV) to view the exact location of the lesion as a guide for needle biopsy. In order to validate our proposed 3D localization system, a set of breast lesions, which appear both in mammograms and in MR Images is used for experiments where the depth of clustered microcalcifications can be verified by the MR images.

We aimed to determine how to approach the axilla after finding a positive sentinel node (SN) for a woman with breast cancer in Taiwan. We used blue dye staining to identify the SN in 824 procedures on 811 patients with breast cancer small than 3 cm by a single surgeon. All patients underwent SN biopsy, followed by at least level II axillary dissection. All SNs were evaluated histologically and immunohistochemically with anti-cytokeratin antibodies. Non-SNs were examined by routine histology. SNs were identified in 814/824 procedures (98.8%). SN metastases were found in 286/814 (35.1%). Subsequent axillary dissections revealed tumors in non-SNs in 188 (65.7%) of these patients. There was a relatively high incidence of non-SN metastases in our population. Tumor exhibiting high nuclear grading, ER-, PR-, Erb-2/neu overexpression, lymphovascular invasion, increasing tumor size, multiple positive SNs, and macrometastatic size in SNs (> 2 mm) were all significantly correlated with non-SN metastases. Multivariate analysis showed that tumor size, the number of positive SNs, and the metastatic size in SNs were independent factors predicting the presence of positive non-SNs. Small (< 2 cm) cancers, having only micrometastatic foci in the SN and having only one SN involved are closely correlated with the tumor-free non-SNs. Our data will assist such patients regarding the need for axillary dissection after finding a positive SN.

Receiver operating characteristics (ROC) has been widely used as a performance evaluation tool to measure effectiveness of medical modalities. It is derived from a standard detection theory with false alarm and detection power interpreted as false positive (FP) and true positive (TP) respectively in terms of medical diagnosis. The ROC curve is plotted based on TP versus FP via hard decisions. This paper presents a three dimensional (3D) ROC analysis which extends the traditional two-dimensional (2D) ROC analysis by including a threshold parameter in a third dimension resulting from soft decisions, (SD). As a result, a 3D ROC curve can be plotted based on three parameters, TP, FP and SD. By virtue of such a 3D ROC curve three two-dimensional (2D) ROC curves can be derived, one of which is the traditional 2D ROC curve of TP versus FP with SD reduced to hard decision. In order to illustrate its utility in medical diagnosis, its application to magnetic resonance (MR) image classification is demonstrated.

The role of the familial breast cancer susceptibility genes, BRCA1 and BRCA2, in the homologous recombination pathway for DNA double-strand break (DSB) repair suggests that the mechanisms involved in DNA DSB repair are of particular etiological importance during breast tumorigenesis. However, there is currently no evidence for an association between breast cancer and the other DSB repair pathway, the nonhomologous end-joining (NHEJ) pathway. It is possible that, because this DNA repair pathway is so crucial for mammalian cells to maintain genomic stability, any severe defects in it would result in serious outcomes, such as genomic instability and cell death, and block subsequent cell outgrowth and tumor formation. Thus, only subtle defects arising from low-penetrance alleles would escape lethality accumulating essential genetic changes and be associated with cancer formation, and the tumorigenic contribution of these alleles would become more obvious if individual putative high-risk genotypes of each NHEJ gene act jointly. Furthermore, this joint effect might be modified by specific environmental factors, and we hypothesized that estrogen exposure might be one such factor because estrogen is suggested to cause DNA DSBs, triggering breast tumorigenesis. Because single nucleotide polymorphisms (SNPs) are the most subtle genetic variation in the genome, to examine these hypotheses, we have genotyped 30 SNPs in all five NHEJ genes (Ku70, Ku80, DNA-PKcs, Ligase IV, and XRCC4) in 254 primary breast cancer patients and 379 healthy controls. Support for these hypotheses came from the observations that (a) two SNPs in Ku70 and XRCC4 were associated with breast cancer risk (P < 0.05); (b) a trend toward increased risk of developing breast cancer was found in women harboring a greater number of putative high-risk genotypes of NHEJ genes (an adjusted odds ratio of 1.46 for having one additional putative high-risk genotype; 95% confidence interval, 1.19-1.80); (c) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to be more susceptible to estrogen, i.e., those with no history of full-term pregnancy; and (d) the protective effect conferred by a history of full-term pregnancy was only significant in women with a lower number of putative high-risk genotypes of NHEJ genes. Based on comprehensive NHEJ gene profiles, this study provides new insights to suggest the role of the NHEJ pathway in breast cancer development and supports the possibility that breast cancer is initiated by estrogen exposure, which causes DNA DSBs.

A new shape recognition-based neural network built with universal feature planes, called Shape Cognitron (S-Cognitron) is introduced to classify clustered microcalcifications. The architecture of S-Cognitron consists of two modules and an extra layer, called 3D figure layer lies in between. The first module contains a shape orientation layer, built with 20 cell planes of low level universal shape features to convert first-order shape orientations into numeric values, and a complex layer, to extract second-order shape features. The 3D figure layer is a feature extract-display layer that extracts the shape curvatures of an input pattern and displays them as a 3D figure. It is then followed by a second module made up of a feature formation layer and a probabilistic neural network-based classification layer. The system is evaluated by using Nijmegen mammogram database and experimental results show that sensitivity and specificity can reach 86.1 and 74.1%, respectively.

The purpose of this study is to report the results of sentinel node (SN) biopsy for assessment of early breast cancer in Taiwan and to compare our results with those in other Asian countries and worldwide. We used methylene blue dye to identify SN in patients with clinically non-palpable breast mass and palpable breast mass smaller than 3 cm. We also explored the role of imprint cytology and immunochemical studies to identify metastatic cancer cells in the lymph nodes. A total of 221 procedures on 218 patients were performed by a single surgeon. The SN was identified in 85.5% of the cases. The overall accuracy of identifying tumors in SN was 97.4%, with a sensitivity of 90.9%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 96.4%. The use of immunochemical techniques helped to identify micrometastasis in SN or non-SN. Our results on SN biopsy with the dye method were similar to those reported from Japan and elsewhere. We concluded that sentinel node biopsy, together with the use of immunochemical techniques to identify micrometastatic foci, has allowed surgeons to decide at the time of surgery whether to perform axillary node dissection.

Cobaltohemoglobin prepared from horse hemoglobin retains the full heterotropic linkage properties of the normal iron hemoglobin, including both the Bohr and phosphate effects. From this result, and the known connection between heterotropic linkage properties and hemoglobin conformational change, it is concluded that cobaltohemoglobin undergoes a quaternary structure transition upon oxygenation. Thus, the stereochemical changes that occur upon oxygen binding to cobalt, as well as to iron, must be compatible with the mechanism triggering such a transition.