Radiomics-based model for predicting pathological complete response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

AIM: To develop and validate a radiomics-based model for predicting response to neoadjuvant chemotherapy (NAC) using baseline computed tomography (CT) images in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: A radiomics signature for predicting pathological complete response (pCR) was developed using radiomics features selected by a random forest classifier on baseline CT images, and imaging predictors were identified in the training set (87 patients). By incorporating imaging predictors and radiomics signature, an imaging-based model was constructed using multivariate logistic regression analysis and validated in an independent validation set consisting of 48 patients with CT from outside institutions. The performance and clinical usefulness of the imaging-based model for predicting pCR were evaluated using area under the receiver operating characteristic curve (AUC) and decision curve analysis. Using a cut-off determined in the training set, the positive likelihood ratios of the imaging-based model were calculated and compared with imaging and histological predictors. RESULTS: The radiomics signature was developed based on six stable radiomics features. An imaging-based model incorporating radiomics signature, tumour shape, tumour size, and clinical stage showed good performance for predicting pCR in both the training (AUC, 0.85; 95% confidence interval [CI], 0.78-0.93) and validation (AUC, 0.75; 95% CI, 0.60-0.86) sets, providing a larger net benefit in decision curve analysis. The imaging-based model showed a higher positive likelihood ratio (1.91) for pCR than imaging and histological predictors (1.33-1.63). CONCLUSIONS: The radiomics-based model using baseline CT images may predict the response of patients with MIBC to NAC.

The robustness of T2 value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI.

PURPOSE: To evaluate the robustness of MR transverse relaxation times of trabecular bone from spin-echo and gradient-echo acquisitions at multiple spatial resolutions of 7 T. METHODS: The effects of MRI resolutions to T2 and T2* of trabecular bone were numerically evaluated by Monte Carlo simulations. T2 , T2*, and trabecular structural indices from multislice multi-echo and UTE acquisitions were measured in defatted human distal femoral condyles on a 7 T scanner. Reference structural indices were extracted from high-resolution microcomputed tomography images. For bovine knee trabecular samples with intact bone marrow, T2 and T2* were measured by degrading spatial resolutions on a 7 T system. RESULTS: In the defatted trabecular experiment, both T2 and T2* values showed strong ( |r| > 0.80) correlations with trabecular spacing and number, at a high spatial resolution of 125 µm3 . The correlations for MR image-segmentation-derived structural indices were significantly degraded ( |r| < 0.50) at spatial resolutions of 250 and 500 µm3 . The correlations for T2* rapidly dropped ( |r| < 0.50) at a spatial resolution of 500 µm3 , whereas those for T2 remained consistently high ( |r| > 0.85). In the bovine trabecular experiments with intact marrow, low-resolution (approximately 1 mm3 , 2 minutes) T2 values did not shorten ( |r| > 0.95 with respect to approximately 0.4 mm3 , 11 minutes) and maintained consistent correlations ( |r| > 0.70) with respect to trabecular spacing (turbo spin echo, 22.5 minutes). CONCLUSION: T2 measurements of trabeculae at 7 T are robust with degrading spatial resolution and may be preferable in assessing trabecular spacing index with reduced scan time, when high-resolution 3D micro-MRI is difficult to obtain.

Clinical relevance of lymph node ratio in breast cancer patients with one to three positive lymph nodes.

BACKGROUND: To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT). METHODS: Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR). RESULTS: Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17-0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT. CONCLUSION: This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.

Elevated levels of preoperative CA 15-3 and CEA serum levels have independently poor prognostic significance in breast cancer.

BACKGROUND: To evaluate the prognostic value of preoperative tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA), in breast cancers. PATIENTS AND METHODS: Preoperative CA 15-3 and CEA levels of 1681 patients were measured. The association of both tumor markers levels with clinicopathological parameters and outcomes was investigated by univariate and multivariate analyses. RESULTS: Among 1681 patients, elevated preoperative CA15-3 and CEA levels were identified in 176 and 131 patients, respectively. Higher preoperative CA 15-3 and CEA levels were significantly associated with a larger tumor size, axillary node metastases, and advanced stage. Patients with elevated CA 15-3 and CEA levels showed worse survival, even in stage-matched analysis. Patients with normal levels of both CA15-3 and CEA showed better survival than those with one or both markers levels elevated. In multivariate analysis, elevated preoperative CA 15-3 and CEA levels were independent prognostic factors. The statistical significance of elevated preoperative tumor markers levels on survival was solidified with longer follow-up and larger study population. CONCLUSIONS: Elevated preoperative CA 15-3 and CEA levels are associated with tumor burden and showed independent prognostic significance. Therefore, new treatment strategies are necessary for patients with elevated preoperative CA 15-3 and CEA levels in clinical practice.

False negative results in axillary lymph nodes by ultrasonography and ultrasonography-guided fine-needle aspiration in patients with invasive ductal carcinoma.

PURPOSE: For preoperative evaluation of ALN status using various methods, axillary US and subsequent US-FNA targeting the LNs suspicious for metastasis are the most widely used methods. The purpose of our study was to assess the rate of false-negative results at preoperative ultrasonography (US) and ultrasonography guided fine needle aspiration (US-FNA) of axillary lymph nodes (ALNs) in breast cancer patients and the number of false-negative lymph nodes, and to evaluate factors related to ALN false negative results in US and/or US-FNA in patients diagnosed with invasive ductal carcinoma. MATERIALS AND METHODS: Among 317 patients who underwent surgery for invasive ductal carcinoma during 2009 in Severance hospital, 237 patients had no reported ALN metastasis on preoperative US-FNA and US. We retrospectively reviewed the subsequent surgical pathology and clinicopathologic findings and assessed the rate of false-negative results from US and US-FNA of ALN and the number of false-negative lymph node. We performed univariate analysis and multivariate logistic regression analysis to evaluate the relationships between variable clinicopathologic factors (T-stage, position of ALN, hormone receptors, histologic grade, lymphovascular invasion (LVI) and performance of FNA) and cytologic results (false-negative result; FNALN and true negative result; TNALN) from US and/or US-FNA of ALN. RESULTS: The rate of false-negative results was 42.4 % (59/139) in both US and US-FNA of ALN but among them, 57.6 % (34/59) showed only one metastatic ALN. Breast cancer with FNALN on US and US-FNA was significantly related to positive estrogen receptor (p = 0.003), positive progesterone receptor (p = 0.001), and the presence of LVI (p = 0.004) in univariate analysis. In multivariate analysis, high T stages (≥ T2, odds ratio (OR) 4.007, p = 0.004) and LVI (OR 7.951, p = 0.001) showed significant correlation with FNALN on US and US-FNA. CONCLUSION: More than half of patients with FNALN showed only one metastatic ALN. LVI and high T-stages were the most important factors attributed to FNALN on US and US-FNA in patients with invasive ductal carcinoma.

Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers.

BACKGROUND: The objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers. PATIENTS AND METHODS: We investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR. RESULTS: AR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Cox's models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC. CONCLUSIONS: AR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors.

The diagnosis of non-malignant papillary lesions of the breast: comparison of ultrasound-guided automated gun biopsy and vacuum-assisted removal.

AIM: To compare the histological upgrade rate of ultrasound (US)-guided vacuum-assisted removal (VAR) and US-14 G-automated core needle biopsy (ACNB) in the diagnosis of papillary breast lesions. MATERIALS AND METHODS: Two hundred and seventy-one biopsies of 230 papillary lesions were examined, which underwent subsequent surgical excision or long-term follow-up after US-ACNB (n = 206) or US-VAR (n = 65). The false-negative and atypical papilloma underestimation rate were compared between the ACNB and VAR groups. Patient and lesion characteristics were collected. The histological upgrade rates of the diagnosis were estimated and compared. RESULTS: Out of 271 papillary lesions, 195 (80.0%) were benign, 21 (7.7%) were atypical, and 55 (20.3%) were malignant. There were no false negatives or underestimated atypical papillomas in the VAR group. However, in the ACNB group, the false-negative rate was 7.6% (12 of 157 benign papillomas, 95% CI; 4.4-12.9%, p = 0.039) and the atypical papilloma underestimation rate was 33% (five of 15 atypical papillomas, 95% CI; 15.2-58.3%, p = 0.135). The histological upgrade rates of the diagnosis for papillary breast lesions were 0% for the VAR (0 of 66) group and 10.2% for the ACNB (21 of 206) group before adjusting for the population (p = 0.003). CONCLUSIONS: ACNB was associated with significantly higher false-negative and histological upgrade rates of diagnosis for papillary breast lesions than VAR.

Expression of androgen receptors in primary breast cancer.

BACKGROUND: To investigate the clinicopathological significance of androgen receptor (AR) expression in primary breast cancers. PATIENTS AND METHODS: We evaluated AR using immunohistochemistry from 413 whole sections from January 2008 to March 2009 and analyzed the relationship between AR and clinicopathological parameters. Tumors with >/=10% nuclear-stained cells were considered to be positive for AR. The differences among variables were calculated by chi-square test. RESULTS: The expression rate of AR was 72.9% higher than those of estrogen receptors (ER) and progesterone receptors. AR expression was significant in patients with no elevated preoperative serum cancer antigen 15-3 levels, smaller tumor size, lower histologic grade and hormone receptor-positive and non-triple-negative breast cancer. However, AR expression was observed in 35% of triple-negative cancers. Metaplastic, medullary and mucinous types of carcinomas showed less AR expression. In the ER-negative subgroup, AR was significantly correlated with human epidermal growth factor receptor type 2 (HER-2) overexpression. CONCLUSIONS: AR is expressed in a significant number of breast cancers and is associated with lower tumor burden and favorable differentiation. There are many issues to be further investigated such as whether AR is an independent prognostic factor, whether it is a therapeutic target for the triple-negative breast cancers and whether it is associated with HER-2 signaling in ER-negative tumors.

Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer outcomes.

BACKGROUND: To investigate the association between tumor markers [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] and clinicopathological parameters and patient outcomes in breast cancer. MATERIALS AND METHODS: A total of 740 patients with stages I-III breast cancer had preoperative CA 15-3 and CEA concentrations measured. Univariate and multivariate analyses were used to investigate associations between marker concentration and clinicopathological parameters and patient outcomes. RESULTS: Among 740 patients, elevated preoperative levels of CA 15-3 and CEA were identified in 92 (12.4%) and 79 (10.7%) patients, respectively. Tumor size (>5 cm), node metastases (> or =4), and advanced stage (> or =III) were associated with higher preoperative levels. Elevated CA 15-3 and CEA levels were associated with poor disease-free survival (DFS, P = 0.0014, P = 0.0001, respectively) and overall survival (OS, P = 0.018, P = 0.015) even in stage-matched analysis. Patients with normal levels of both CA 15-3 and CEA showed better DFS and OS than those with elevated group. In multivariate analysis, age (<35 years), tumor size (>2 cm), node metastases, estrogen receptor expression, and elevated CA 15-3 and CEA preoperative values were independent prognostic factors for DFS. CONCLUSION: High preoperative CA 15-3 and CEA levels may reflect tumor burden and are associated with advanced disease and poor outcome. Measuring preoperative levels of CA 15-3 and CEA can be helpful for predicting outcomes.

Co-expression of nerve growth factor and p75NGFR in the inferior alveolar nerve after mandibular distraction osteogenesis.

During mandibular distraction osteogenesis (DO), the inferior alveolar nerve (IAN) is damaged during distractor activation, but spontaneously recovers during consolidation. Although many neurotrophic factors are known to play critical roles, there have been few studies on the mechanism of peripheral nerve recovery after DO. The aim of this study was to observe the expression pattern of p75NGFR (low-affinity receptor of NGF) and to detect autocrine growth activity in IANs following mandibular DO. Unilateral mandibular distractions (0.5mm each, twice per day for 10 days) were conducted on eight mongrel dogs. Two each were killed at 7, 14, 28 and 56 days after completing distraction. The distracted IAN and contralateral control nerve were harvested. Immunohistochemical staining was performed to determine p75NGFR expression, and double immunofluorescent staining to detect NGF and p75NGFR co-expression. Levels of p75NGFR expression were found to be significantly elevated at 7 and 14 days in Schwann cells located in the outer layer of axon, but were almost undetectable at 28 and 56 days. In double immunofluorescent images, the co-expression of NGF and p75NGFR was also detected at 7 and 14 days. p75NGFR plays an important role in remyelination due to its abundant expression in Schwann cells of damaged nerves, and NGF is an autocrine growth factor present in distracted IANs during the early consolidation period after mandibular DO.

Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo.

Monoclonal antibodies specific for the p185HER2/neu growth factor receptor represent a significant advance in receptor-based therapy for p185HER2/neu-expressing human cancers. We have used a structure-based approach to develop a small (1.5 kDa) exocyclic anti-HER2/neu peptide mimic (AHNP) functionally similar to an anti-p185HER2/neu monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185HER2/neu with high affinity (KD=300 nM). This results in inhibition of proliferation of p185HER2/neu-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185HER2/neu-expressing tumors in athymic mice. In addition, the mimetic sensitizes the tumor cells to apoptosis when used in conjunction with ionizing radiation or chemotherapeutic agents. A comparison of the molar quantities of the Herceptin antibody and the AHNP mimetic required for inhibiting cell growth and anchorage-independent growth showed generally similar activities. The structure-based derivation of the AHNP represents a novel strategy for the design of receptor-specific tumor therapies.

Expression of vascular endothelial growth factor and its receptors after mandibular distraction osteogenesis.

During distraction osteogenesis, angiogenic activity is essential for new bone formation. This study examined the expression of vascular endothelial growth factor (VEGF) and two of its receptors, Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2), in cellular components after mandibular distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in six mongrel dogs. Two animals each were killed on days 7, 14 and 28 after completion of distraction. The distracted mandibular segments and contralateral undistracted control segments were harvested and processed for immunohistochemical examination. Seven days after distraction, there was a significant increase in the expression levels of VEGF and its receptors in the osteoblasts, osteocytes and immature fibroblast-like cells compared to control specimens. These levels were maintained for 14 days after distraction in the osteoblasts and fibroblast-like cells. Twenty-eight days after distraction, VEGF and VEGFR-1 were expressed only moderately/weakly in the osteoblasts, and no VEGFR-2 expression was detected in the cellular component of the distracted bone. Throughout the observation period, VEGFR-1 expression was stronger than that of VEGFR-2. The expression patterns of VEGF and its receptors suggest that it plays an important role in osteogenesis, and that osteoblasts and immature fibroblast-like cells of the distracted bone may have an autocrine growth effect during distraction osteogenesis.

Intraoperative examination of sentinel lymph nodes by immunohistochemical staining in patients with breast cancer.

AIM: To performed a prospective investigation of the relative merits of rapid cytokeratin immunohistochemical (CK-IHC) staining of the SLN removed during the operation of breast cancer patients. STUDY DESIGN: Between December 2002 and March 2004, 62 patients with T1 and T2 breast cancer were enrolled after undergoing successful sentinel lymph node biopsy. Eighty-nine sentinel lymph nodes (mean number, 1.44) were biopsied and first examined by hematoxylin-eosin (H&E) stained frozen section. All the tumour free sentinel lymph nodes by H&E stained frozen section were immunostained for cytokeratin using a rapid immunohistochemical assay (Cytokeratin (PAN), 1:50, Novocastra Lab., Newcastle, UK) during the operations. RESULTS: Rapid IHC staining revealed seven positive sentinel lymph nodes that were negative for metastasis by H&E staining. This study showed a sensitivity of 92.86%, a specificity of 100%, an accuracy of 98.9%, and a negative predictive value of 98.7%. CONCLUSIONS: The intraoperative examination of sentinel lymph nodes is an accurate and effective way of predicting the axillary lymph node status of patients with breast cancers.

Expression of nerve growth factor and vascular endothelial growth factor in the inferior alveolar nerve after distraction osteogenesis.

The objective of this study was to evaluate changes occurring in the inferior alveolar nerve (IAN) subsequent to mandibular distraction osteogenesis, with regard to the expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Unilateral mandibular distractions (0.5mm each, twice per day for 10 days) were conducted on 8 mongrel dogs. Two animals were killed at 7, 14, 28 and 56 days after completion of distraction. The distracted IAN and contralateral control nerve were then harvested and analysed histologically and immunohistochemically. Signs of acute nerve injury, including demyelination, were observed in the distracted IAN on the 7th and 14th day after distraction. At 56 days, the histological features of the distracted IAN were similar to those of the control nerve. The levels of NGF and VEGF expression were significantly elevated on the 7th and 14th day after distraction. NGF was expressed in most of the distracted nerve tissues, but VEGF was primarily detected in Schwann cells and the neurovasorum. VEGF expression had returned to normal but NGF expression was still profoundly elevated 28 days after distraction. NGF expression returned to normal levels at 56 days after distraction. NGF and VEGF appeared to have been elicited from the Schwann cells and damaged nervous tissues, and they may play important roles in the initial healing of damaged nerves. VEGF expression returned to normal more quickly than did NGF expression. This may indicate that hypoxic conditions within the distracted nerve had recovered to normal during the early stages of consolidation. Micro-vessels in the distracted nerve may have recovered more rapidly than did the nerve tissue itself.

[Functional variability of the autocorrelation structure of the EEG].

On an example of records EEG of 39 healthy subjects, the quantitative analysis of variability of the autocorrelation structure of one-second EEG segments was carried out on the basis of comparison of structural functions constructed for these segments. It was shown that more than 30% of cases, statistically significant sifferences were observed between the structural functions of successive one-second EEG segments shifted by 1-3 s, as compared to surrogate EEGs formed with the tangled random sequence of count points. On the basis of the obtained data, the index of nonstationarity of the EEG autocorrelation structure was proposed. This index can be used for the objective quantitative evaluation of the functional states of the human brain.

Cloning and characterization of the citA gene encoding the mitochondrial citrate synthase of Aspergillus nidulans.

We isolated a citrate synthase gene (citA) from Aspergillus nidulans. By analysis of the protein coding region, citA was shown to encode a citrate synthase (CitA) of 52.2 kDa consisting of 474 amino acid residues that were interrupted by seven introns. Also, the precursor CitA protein was revealed to have an N-terminal mitochondrial targeting signal of 35 amino acid residues containing an R-3 cleavage motif, R(32)-C-Y decreases S(35), which supports the fact that citA encodes the mitochondrial form of citrate synthase of A. nidulans. Southern blot analysis showed that citA is present as a single copy in the genome.

Comparison of PCR/nucleic acid hybridization and EIA for the detection of Chlamydia trachomatis in different populations in a regional centre.

Culture on McCoy cell monolayers has been accepted as the reference method for the detection of Chlamydia trachomatis. Recent studies have shown that polymerase chain reaction (PCR)/nucleic acid hybridization based methods have increased sensitivity over culture while still retaining specificity. In situations where organism viability is of concern, due to factors such as transportation delays, culture is inappropriate. Regional laboratories therefore have not been able to utilize the reference method and have been forced to use less reliable methods. The aims of our study were to assess the feasibility of performing PCR to diagnose infections due to C. trachomatis in a regional laboratory using a new commercial kit--Amplicor (Roche Molecular Systems, Branchburg, NJ) and to compare the current enzyme-immunoassay (EIA) based-methods used in our laboratory (VIDAS [bioMerieux Vitek, Hazelwood MO] and IDEIA [Novo Nordisk Diagnostics, Cambridge, UK]) against PCR. Thirteen positive Amplicor specimens were found in 267 urine specimens collected from asymptomatic adolescent males and females. All 13 were confirmed positive using major outer membrane protein gene PCR (MOMP). VIDAS and IDEIA showed 100% correlation to each other but only detected 5/13 positives. Of 140 consecutive patients attending the regional sexual health clinic, 13 were Amplicor positive, 11/13 MOMP positive and 10/13 positive by VIDAS. Five of 254 patients attending the hospital antenatal clinic were positive by Amplicor, all being confirmed by MOMP. No PCR inhibition was detected in a random sample of 100 varied negative Amplicor tests using a modification of the Amplicor kit. No contamination was experienced. The Amplicor kit was shown to be suitable for use in the routine clinical laboratory with minimal disruption to workflow. For regional laboratories this kit should provide more accurate results than EIA based methods, particularly in the detection of asymptomatic persons.

Pyriform sinus fistula.

Three patients had cervical draining sinus communicating with the pyriform sinus and one patient had acute suppurative thyroiditis resulting from infection through the pyriform sinus. There was a moderate to severe perithyroidal inflammation in all 4 cases. The age of onset ranged from 7 to 18 years old (mean; 12) but that of confirmation 9, 15, 18 and 67 years of age. Three of the patients were male and 3 of the cases involved the left side. All patients had suffered from several recurrences of cervical abscess, ranged from 2 to 7 times (mean; 4). Characteristic clinical features included 1) onset at a young age 2) frequent recurrence unless the fistula was extirpated completely 3) presenting with cervical draining sinus after repeated incision and drainage. It is supposed that the fistula is a route of infection mainly in the perithyroidal space and subsequently into the thyroid gland. When the fistula communicates directly with the thyroid gland, it can cause primary acute suppurative thyroiditis. Chronic cervical draining sinus with histories of repeated incision and drainage may be the clue to the diagnosis. A barium paste swallow study is the radiologic procedure of choice and complete removal of the fistula is the treatment of choice.

Clinical breast examination for screening of asymptomatic women: the importance of clinical breast examination for breast cancer detection.

Of 489 asymptomatic women who were referred to our institute from other screening clinics, 46 were eventually proven to be breast cancer patients, and this number equated to 8.1% of the 565 breast cancer patients treated in our institute during the period of January 1997 to December 1998. Among the 46 cancer patients of the initial 489 asymptomatic women, twenty-five (54.35%) were detected by mammogram alone, six (13.04%) by clinical breast examination (CBE) alone, and the remaining 15 (32.61%) by both mammogram and CBE. In context with age, the mammographic sensitivity for cancer detection was 100% for women aged over 60, 91% for 50s, 78.9% for 40s, and 75% for 30s, and inversely correlated with the patient's age. Among the 25 cancers detected by mammogram alone, 18 (72%) belonged to DCIS or stage I. In contrast, four (66.7%) of six cancers detected by CBE alone and nine (60%) of 15 cancers by both CBE and mammography were included in stage IIa or IIb. However, the total incidence of early cancers (stages 0 and I) was significantly higher in the screening group than in the symptomatic group (p < 0.01). These results suggest that the role of mammography is important in the detection of cancers in their earlier stage and CBE is helpful in reducing false negative results in breast cancer screening. In conclusion, film mammography is the best tool for the detection of microcalcification and is useful for the detection of earlier lesions, but is not perfect for the detection of breast cancer particularly in young women. A careful CBE is an essential part of breast screening in order to reduce false-negative results.