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Background: This retrospective observational study validated nuclear grading criteria developed to identify a high-risk group with recurrence rate ≥20-30% and local pathology diagnosis used in a previous multi-institutional randomized N·SAS-BC 01 trial, where the efficacy of adjuvant chemotherapy regimens was evaluated in 733 high-risk node-negative invasive breast cancer patients., Methods: Of 545 patients with long-term follow-up data (median 12.1 years), pathology slides, and local pathology diagnosis, 530 eligible patients were subjected to central pathology review (CPR) for histological type and nuclear grade (NG). Concordance in NGs was compared with local diagnosis. The 10/15-year recurrence-free survival (RFS) and overall survival (OS) rates stratified by NG and histological type were calculated., Results: Local diagnoses were invasive ductal carcinoma (IDC)-NG2, IDC-NG3, invasive lobular carcinoma (ILC), and metaplastic carcinoma (MC) in 158/327/38/7 patients, respectively. The 10/15-year RFS rates were 87.2/82.6% for IDC-NG2 and 81.8/75.0% for IDC-NG3 (p = 0.061), and OS rates were 95.0/92.8% for IDC-NG2 and 90.8/85.7% for IDC-NG3 (p = 0.042). CPR graded 485 locally diagnosed IDCs as IDC-NG1/NG2/NG3/unknown in 98/116/267/4 patients, respectively. No significant difference was found among survival curves for the three NG groups. Although the agreement level between local and CPR diagnoses was low (κ = 0.311), both diagnoses identified a patient group with a 15-year recurrence rate ≥ 20%. The 10/15-year RFS rates were 79.4/63.5% for ILC and 68.6%/unknown for MC., Conclusions: The N·SAS grading system identified a patient group with high-risk node-negative invasive breast cancer, suggesting that local diagnosis was performed efficiently in the N·SAS-BC 01 trial., Trial Registration Number: UMIN000022571. Date of registration: June 1, 2016., (© 2022. The Author(s).)

Background: Although Ki67 has important clinical relevance in breast cancer, its assessment results vary according to assay due to differences in both analytical and interpretation processes. We aimed to validate the performance of anti-Ki67 antibody clone 30-9 by comparison with clone MIB-1 and to investigate utility of the image analysis system in Ki67 assessment using clinical breast cancer samples., Methods: A series of sequential tissue sections was prepared from formalin-fixed paraffin-embedded blocks of surgically resected breast cancer specimens from 50 patients. The tissue sections were stained immunohistochemically with anti-Ki67 antibodies, 30-9 and MIB-1, as well as with hematoxylin and eosin for morphological analysis. We scanned all the stained slides with Ventana iScan HT and selected the Ki67 counting areas based on morphological findings. Three pathologists independently studied images of the counting areas to determine Ki67-positive rates. In addition, the images of 30-9-stained slides were analyzed using the image analysis system, VENTANA Virtuoso., Results: Ki67-positive rates by 30-9 showed a strong correlation with those by MIB-1 for all pathologists (pathologist #1: r = 0.985, pathologist #2: r = 0.987, pathologist #3: r = 0.982). Between 30-9 and MIB-1, there was no significant difference of CV%, showing variabilities of Ki67-positive rates among pathologists. Ki67-positive rates showed a strong correlation between the image analytical values and the pathologist-counted median values (r = 0.952)., Conclusions: The performance of 30-9 is equivalent to that of MIB-1 in Ki67 assessment of breast cancer. The image analysis system can substitute for or support visual counting by a pathologist.

Background: The degree of pathological response to neoadjuvant chemotherapy (NAC) was correlated with the prognosis in breast cancer. There are few studies published on inter-observer variability in the assessment of pathological responses among pathologists., Methods: We collected 64 surgically resected specimens from patients who had received NAC. Three pathologists assessed the pathological responses and classified them into 7 grades according to grading system of the Japanese Breast Cancer Society. The levels of concordance among pathologists were categorized into 3 classes: full concordance (all pathologists gave the same grade), partial concordance (two of them gave the same grade), and discordance (all three gave different grades). The inter-observer agreement among pathologists was estimated using the percentage concordance and Cohen's kappa statistics., Results: Full concordance, partial concordance, and discordance were seen in 28 (43%), 33 (52%), and 3 (5%) specimens, respectively. In most of partial concordance specimens (30 out of 33), the pathological response grades differed by only one level. The kappa value was 0.59. The concordance rate with regard to pCR was 97%., Conclusions: Most of the judgments among pathologists differed within one level, but there is room for improving harmonization in the assessment of pathological responses.

Background: Axillary dissection omission for sentinel lymph node-negative patients has been a practice at Cancer Institute Hospital, Japanese Foundation for Cancer Research since 2003. We examined the long-term results of omission of axillary dissection in sentinel lymph node-negative patients treated at our hospital, as well as their axillary lymph node recurrence characteristics and outcomes., Methods: Our study included 2,578 patients with cTis or T1-T3N0M0 primary breast cancer for whom dissection was omitted because they were sentinel lymph node negative. The median observation period was 75 months., Results: In sentinel lymph node-negative patients for whom dissection was omitted, the rates of axillary lymph node recurrence, distant recurrence, and breast cancer mortality were 0.9, 2, and 1 %, respectively. Eighteen patients underwent additional dissection if axillary lymph node recurrence was observed at the first recurrence. Four triple-negative (TN) patients experienced distant recurrence after additional dissection. All four patients were administered anticancer agents after axillary lymph node recurrence and experienced recurrence within 1 year of additional dissection. The axillary lymph node recurrence rate was 0.8 % for luminal and 4.5 % for TN subtypes., Conclusions: The long-term prognoses of patients for whom dissection was omitted owing to negative sentinel lymph node metastases were similar to those reported previously-low recurrence and mortality rates. The frequency of axillary lymph node recurrence and the post-recurrence outcome differed between luminal and TN cases, with recurrence being more frequent in patients with the TN subtype. TN patients also had poorer prognoses, even after receiving additional dissection and anticancer agents after recurrence.

Background: Although human epidermal growth factor receptor 2 (HER2) is a significant clinical biomarker for breast cancer, the HER2 testing involves a complicated evaluation process. We devised an easy method for HER2 gene testing and investigated its utility., Methods: HER2 testing was performed by immunohistochemistry (IHC) and dual-color in situ hybridization (DISH) on surgical specimens from 50 patients with invasive breast cancer. DISH was evaluated by two methods. One was the DISH count method in which the HER2 and CEP17 signals were counted and the HER2/CEP17 signal ratio was calculated. The other was the DISH-easy method in which pathologists only observed slices without counting the signals. The DISH-easy method was performed by two pathologists. We analyzed the correlations between the DISH-easy method and the DISH count method by each pathologist and calculated the inter-observer concordance rate of the DISH-easy method., Results: The results from two pathologists using the DISH-easy method corresponded to the IHC results (P < 0.01) and the DISH count method results (P < 0.01). All cases determined to be negative using the DISH-easy method were also negative via the DISH count method with a corresponding rate of 100 % for both pathologist A (34/34) and B (32/32). Most of the results for the positive cases also corresponded; the correspondence rate of pathologist A was 100 % (8/8) and 89 % for B (8/9). The inter-observer concordance rate was 81 % (κ = 0.65)., Conclusions: The DISH-easy method is simple and useful for HER2 testing regardless of proficiency of the evaluators.

Highly malignant tumors express high levels of the minichromosome maintenance 2 (MCM2) protein, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In a previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70 bound MCM2, impaired its nuclear translocation, and enhanced DNA-damage-induced apoptosis in FLV-infected hematopoietic cells when the cells expressed high levels of MCM2. Here, we show that MCM2 is highly expressed in clinical samples of invasive carcinoma of the breast, especially triple-negative breast cancer (TNBC), and in cancer stem cell (CSC) marker-positive breast cancer cells. To generate a cancer therapy model using gp70, we introduced the gp70 protein into the cytoplasm of murine breast cancer cells that express high levels of MCM2 by conjugating the protein transduction domain (PTD) of Hph-1 to gp70 (Hph-1-gp70). Hph-1-gp70 was successfully transduced into the cytoplasm of breast cancer cells. The transduced protein enhanced the DNA damage-induced apoptosis of cancer cells in vitro and in vivo. Therefore, an MCM2-targeted strategy using Hph-1-gp70 treatment to induce DNA damage might be a successful therapy for highly malignant breast cancers such as TNBC and for the eradication of CSC-like cells from breast cancer tissue.

Prediction of subsequent risks of breast carcinoma (BC) development in intraductal papilloma (IDP) has remained controversial with the exception of atypical papilloma (AP). The potential value of immunohistochemistry (IHC) of cytokeratin 5/6 [CK5/6] and p63 have been proposed but its standardization has also remained controversial. We studied 17 patients initially diagnosed as IDP or AP who subsequently developed BC with 34 age-matched controls. We compared histological features, results of IHC (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], p63, CK5/6, Ki67), and ultrasound findings. Univariate conditional logistic regression analysis revealed that the status of both CK5/6 and p63/CK5/6 were significantly associated with subsequent BC development (P < 0.05). BC development in CK5/6 positive patients was 17.9% and p63/CK5/6 double positive patients 8.6%, respectively. Ultrasound evaluation was not significantly associated with any of the parameters examined and subsequent carcinoma development. Despite CK5/6 positivity, the subsequent incidence of BC development was nearly 20%. However p63/CK5/6 double positive status could predict a significantly lower subsequent carcinoma incidence, indicating a more accurate prognostic utility. Combining p63/CK5/6 with histological findings could be easily applied and could predict the subsequent BC development of the patients diagnosed as IDP at biopsy., (© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Immunohistochemical determination of ER/PR status has been the gold standard in clinical practice of breast cancer for decades. A cut-off of '1%' is commonly used; however, this is not supported by strict evidence. How the proportion of ER/PR-positive cells influences the response to endocrine therapy has been scarcely reported, either. To address these issues, 486 and 663 invasive breast cancer cases treated with or without adjuvant tamoxifen respectively (median follow-up period, 12.8 years) were enrolled, and effect of tamoxifen treatment was compared among ER/PR-positive or -negative groups immunohistochemically determined using various cut-offs. Tamoxifen significantly improved 5 years disease-free survival in ER/PR-positive, but not in ER/PR-negative, cases even using immunohistochemical >0% cut-off. Cases with ≥67% ER/PR expressing cells responded to tamoxifen by far the best. Patients having tumors without any ER/PR-positive cells should be excluded from endocrine therapy, whereas this therapy should be strongly recommended for those with ≥67% ER/PR-positive cells., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Atypical ductal proliferation or ADP has been used in histopathological diagnosis of core needle biopsy (CNB) but its details have not been well studied. Therefore, we examined the clinicopathological characteristics of the initial CNB cases diagnosed as 'ADP ' who subsequently turned out to be malignant, and compared the findings to those that did not. Among 101 cases initially diagnosed as ADP in CNB, the second biopsy revealed no carcinoma (38), ductal carcinoma in situ (DCIS) (45) and invasive carcinoma (18). Significant differences were detected between those which turned out to be carcinoma and those that did not, in the status of myoepithelial cells identified by p63 immunohistochemistry (P = 0.026) and ultrasound (US) categories (P < 0.001). We further compared the histopathological characteristics of those initially diagnosed as ADP and subsequently as DCIS or invasive ductal carcinoma (IDC) with those initially diagnosed as such. DCIS or IDC cases initially diagnosed as ADP had significantly lower Ki67 labeling index (P < 0.01, P < 0.01) and histological grade using Van nuys prognostic index (P < 0.01) or Nottingham histological grades (P < 0.01) respectively than those initially as DCIS or IDC. An assessment of myoepithelial components with US findings might contribute to determine the subsequent clinical algorithm of the patients diagnosed as ADP at initial CNB., (© 2014 The Authors. Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Objective: The aim of the present study was to evaluate the usefulness of computed tomographic (CT) imaging in delineating tumor extent and guiding surgical management., Background: The routine use of preoperative magnetic resonance imaging (MRI) is a controversial issue in breast cancer management. Negative studies with regard to the utility of MRI might be due to differences in positioning during imaging and subsequent surgery., Methods: Candidates for breast-conserving surgery were eligible for the study. The surgeons marked the line of planned excision on the skin, which was also recorded on the CT image. Contrast-enhanced breast CT was performed in the supine surgical position. The CT results were used to help determine the extent of resection. The pathological findings were then compared with the CT-guided surgical plans., Results: A total of 297 patients were involved. The surgeons widened the extent of resection in 42 (14.1%, 95% confidence interval 10.1%-18.1%) patients on the basis of the CT findings. Among the 6 patients whose procedures were changed to mastectomy, 4 had pathologically multicentric tumors and 2 had widely spread intraductal components. The remaining 36 patients underwent quadrantectomy instead of wide excision on the basis of the CT images. There were 3 patients in whom conversion from wide excision to quadrantectomy resulted in overexcision. Preoperative breast CT may have reduced the positive margin rate and also correctly changed the extent of surgery in 13.1% of patients., Conclusions: This prospective study suggests that breast CT, carried out in the supine position, is useful in the preoperative determination of the optimal surgical procedure.

Mammary hamartoma is an infrequent, nonmalignant lesion. Only 12 cases of carcinomas associated with a hamartoma have been previously documented in the literature. We describe a case of invasive ductal carcinoma arising in the mammary hamartoma during the follow-up period of a previously diagnosed hamartoma.

Invasive micropapillary carcinoma (IMP) of the breast is a rare variant of invasive breast carcinoma and most cases of IMP are associated with nodal metastasis and lymphatic invasion. Lesions composed of an IMP component alone are rare and almost always coexist with other pathological components. However, few reports have documented IMP along with its proportion and the coexistent pathological type. We analyzed the total 486 breast cancer lesions operated in our hospital in 1998. We classified the lesions into five groups by the proportion of the IMP component in each lesion. Then we evaluated the incidence of nodal metastasis and lymphatic invasion in each group. The incidence of the invasive carcinoma containing any IMP components was 8.4%. The incidence of nodal metastasis and lymphatic invasion in lesions with an IMP component were significantly higher than that in those with no IMP. No correlation was seen between the incidence of nodal metastasis and the coexistent pathological type, shape of tumor clusters, nuclear grade and the expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and gross cystic disease fluid protein-15 in IMP components. The presence of IMP components was a significant predictive factor for nodal metastasis, even if it is detected in only a small proportion of the tumor., (© 2011 The Authors. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.)

Background: Conventional histopathological examination is limited in measuring accurate total metastatic volume in a lymph node. Recently, a molecular-based procedure to detect lymph node metastases, one-step nucleic acid amplification (OSNA) assay, has been developed. OSNA assay can assess a whole lymph node and yields semiquantitative results. The authors compared the performance in intraoperative detection of sentinel lymph node metastases with OSNA assay using a whole lymph node versus routine frozen section (FS) histology with a 2 mm-sectioned lymph node., Methods: Subjects comprised 531 consecutive patients diagnosed with OSNA assay and 618 consecutive patients diagnosed with FS histological examination. The authors compared the sentinel lymph node-positive rate between the OSNA and FS cohorts, and investigated characteristics of patients for whom OSNA could detect metastases but FS could not. OSNA (+) was defined as micrometastasis, and OSNA (++) and (+I) were defined as macrometastasis., Results: OSNA assay detected more cases of sentinel lymph node metastases than FS histology (OSNA 121 of 531, 22.8% vs FS 109 of 618, 17.6%; P = .036), particularly micrometastases (46 of 531, 8.7% vs 28 of 618, 4.5%; P = .0064). There was no difference in macrometastasis detection between OSNA and FS (75 of 531, 14.1% vs 81 of 618, 13.1%; P = .68). OSNA detected more metastases than FS in postmenopausal patients (77 of 302, 25.5% vs 43 of 351, 12.3%; P < .0001), and in tumors without fat invasion (23 of 156, 14.7% vs 6 of 151, 4.0%; P = .012) or lymphovascular invasion (67 of 395, 17.0% vs 45 of 458, 9.8%; P = .042)., Conclusions: Intraoperative OSNA assay detects more sentinel lymph node metastases, particularly micrometastases, than does FS histology. OSNA assay can also detect more metastases in postmenopausal patients or from less aggressive primary tumors compared with FS histology., (Copyright © 2011 American Cancer Society.)

Background: The impact of sentinel lymph node biopsy on breast cancer mimicking ductal carcinoma in situ (DCIS) is a matter of debate., Methods: We studied the rate of occurrence of sentinel lymph node metastasis in 255 breast cancer patients with pure DCIS showing no invasive components on routine pathological examination. We compared this to the rate of occurrence in 177 patients with predominant intraductal-component (IDC) breast cancers containing invasive foci equal to or less than 0.5 cm in size., Results: Most of the clinical and pathological baseline characteristics were the same between the two groups. However, peritumoral lymphatic permeation occurred less often in the pure DCIS group than in the IDC-predominant invasive-lesion group (1.2% vs. 6.8%, p = 0.002). One patient (0.39%) with pure DCIS had two sentinel lymph nodes positive for metastasis. This rate was significantly lower than that in patients with IDC-predominant invasive lesions (6.2%; p < 0.001)., Conclusions: Because the rate of sentinel lymph node metastasis in pure DCIS is very low, sentinel lymph node biopsy can safely be omitted.

Herein is reported a rare case of carcinoma arising from papilloma of the breast. A 63-year-old postmenopausal woman noticed a nodule approximately 1 cm in diameter in her left breast. Ultrasonography indicated a mass with a solid pattern within an intracystic tumor measuring 1.5 x 1.5 x 1.4 cm in diameter located near the left nipple. On total image analysis malignancy could not be denied, therefore lumpectomy with resection of the surrounding tissue was performed. Histologically the tumor consisted of cancerous and papilloma components. The cancer cells had high-grade nuclear atypia, were irregular, and contained abundant eosinophilic cytoplasm with a thin vascular stalk. In contrast, the tumor cells had no atypia, and had a thick stroma in the papilloma components. Both lesions could be distinguished clearly from each other. In addition, a transition from papillary to cancerous elements in some areas was seen. An additional partial mastectomy was performed after the lumpectomy but no carcinoma foci were noted in the excised tissue. Possible occurrence of cancerous change in solitary intraductal papilloma of the breast was suspected.

Introduction: Peripherally localized aromatase, which converts circulating androgens into estrogens, is important in the pathogenesis of postmenopausal breast carcinomas. We have previously shown that aromatase mRNA levels are higher in elderly breast carcinomas (EldCa) than breast carcinomas of the control group (ContCa) or normal breast tissues. Aromatase expression has been reported to be regulated through the alternative use of multiple exons 1 (exons 1a-1f and so on); however, the preferential usage of exons 1 in elderly breast tissue has never been systematically examined. In order to properly treat and protect against EldCa, the regulation mechanism of aromatase expression in elderly breast tissues should be elucidated. The aim of the present study is to elucidate whether there are any specific patterns in use of multiple exons 1 in elderly breast tissue., Methods: Usage of multiple exons 1 of the aromatase gene and mRNA levels of aromatase were examined by reverse transcription-polymerase chain reaction analysis in breast tissues of 38 elderly patients with breast cancer (age 80-99), and the results were compared with those in 35 patients of the control group (age 37-70). One-factor analysis of variance and the Scheffé test were used for the comparison of aromatase mRNA levels. Patterns of preferential utilization of multiple exons 1 of the aromatase gene were compared by chi2 test for independence or Fisher exact test for independence using a contingency table., Results: Exon 1d was utilized much more frequently in elderly tissue than in the control group irrespective of cancerous or normal tissue (EldCa, 36/38, 95% versus ContCa, 7/35, 20%, P < 0.0001; normal tissue of the elderly, EldNorm, 30/34, 88% versus normal tissue of controls, ContNorm, 2/29, 7%, P < 0.0001). Twenty EldCa (53%) and 12 EldNorm (35%) used both exons 1c and 1d; however, their dominance was reversed (EldCa, all 1d > 1c; EldNorm, all 1c > 1d)., Conclusions: Elderly breast tissues exhibited specific patterns in use of multiple exons 1, which at least partly explained the higher aromatase levels in EldCa. The mechanisms of how these specific patterns occur during aging and carcinogenesis should be further examined.

Apocrine carcinoma of the breast, which frequently expresses oestrogen receptor-beta (ER-beta) in the absence of ER-alpha and only infrequently is treated endocrinologically, gives an opportunity to investigate the clinicopathological role of ER-beta in breast cancer independent of ER-alpha expression or tamoxifen treatment. Several isotypes of ER-beta, ER-beta1-5 etc., have been identified thus far; however, the clinicopathological importance of each ER-beta isotype in breast cancer is still uncertain. Here we aimed to clarify the clinicopathological importance of ER-beta1 and ER-betacx (ER-beta2) in apocrine carcinomas, immunohistochemically examining expressions of ER-beta1 and ER-betacx in 47 apocrine carcinomas. Positivity for ER-beta1 and ER-betacx was observed in 41 (87%) and 18 (38%) of 47 cases, respectively. ER-beta1 positivity was related to smaller tumor size (P=0.0359), lower histological grade (P=0.0322), and higher disease-free survival (P<0.0001), whereas ER-betacx status was related to none of these parameters. ER-beta1 positivity was also associated with favorable clinical outcome in 24 so-called triple-negative (ER-alpha-negative/PR-negative/HER2-negative) apocrine carcinomas. ER-beta1 itself, independent of ER-alpha expression and tamoxifen treatment, seems to have a tumor-suppressive effect, at least in apocrine carcinomas. Further study of ER-beta1 is desired to optimize breast cancer treatment.

Background: The impact of skin invasion in node negative breast cancer is uncertain., Methods: We determined the prognosis in 97 node negative breast cancer patients (case group) who had tumors with skin invasion. Then we compared these patients with 4500 node negative invasive breast cancer patients treated surgically in the same period., Results: Patients with skin invasion tended to be older, had more invasive lobular carcinoma and larger tumor size, and were less likely to have breast conserving surgery than those in the control group. The 5-year disease-free survival rate in the case group was 94.0%. There was no significant difference in the 10-year disease-specific overall survival rates in terms of skin invasion in node negative patients (90.7% in the case group, 92.9% in the control group; p = 0.2032)., Conclusion: Results suggest that skin invasion has no impact on survival in node negative invasive breast cancer patients. The adjuvant regimens which the individual institute applies for node negative breast cancer should be used regardless of skin invasion.

Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations. The association between dermatomyositis and malignancy is becoming more clearly delineated. A sort of dermatomyositis is thought to be paraneoplastic syndrome and dermatomyositis may follow clinical course of malignancy. We report a 68-year-old woman with dermatomyositis, whose clinical onset of dermatomyositis was apparently concomitant with breast cancer. Dermatomyositis had settled down and oral steroid could be tapered after the resection of breast cancer. Creatine kinase value was elevated before the detection of the first and second recurrence and in the terminal state. At the second recurrence, skin lesions and creatine kinase value had flared up and immediate metastatic check-up revealed the recurrence. Our case shows dermatomyositis, which was thought to be paraneoplastic syndrome, that followed clinical course of malignancy and suggests immediate check-up is needed for early detection of recurrence when dermatomyositis flares up after the resection of the malignancy.

Purpose: To confirm which modality, ultrasonography (US) or mammography (MMG), is useful to detect breast cancer in women aged 30 to 39 years, and to compare the sensitivity and findings of these two modalities for invasive carcinoma and ductal carcinoma in situ (DCIS) in the diagnostic setting., Methods: We retrospectively evaluated the sensitivity and findings of these two modalities in 165 patients aged 30 to 39 years, who underwent surgery at the Cancer Institute Hospital between 2001 and 2003. US or MMG were performed after obtaining information on the other modalities previously used and physical examination. The abnormal findings of US were defined as mass lesions and focal hypoechoic areas due to breast cancer. The abnormal findings of MMG were defined as category 3 to 5 (Japanese Mammography Guidelines) masses, calcifications, and other findings due to cancer., Results: Of 165 patients, 147 patients (89%) mammographically showed dense breasts. Histologically, 146 (88%) were invasive carcinomas and 19 (12%) were DCIS. In all carcinomas, the sensitivity of US (95%) was higher than that of MMG (85%). The sensitivity of US for invasive carcinoma (99%) was higher than that of MMG (85%). On the other hand, the sensitivity of MMG for DCIS (89%) was much higher than that of US (68%)., Conclusions: US is more sensitive to detect breast cancers than MMG in this age range, especially for invasive carcinoma. On the other hand, MMG is useful for detecting DCIS, especially when it manifests with microcalcifications.

Background: To establish tailor-made therapy for breast cancer, we investigated the possibility of predicting chemotherapy sensitive cases based on pre-therapeutic histological features., Methods: A total of 87 breast cancer patients underwent neoadjuvant chemotherapy with a paclitaxel (80 mg/m(2)/q1w, 12 courses)or an epirubicin regimen (90 mg/m(2)/q3wks, 4 courses). We investigated the chemo-sensitivity of invasive ductal carcinoma, solid-tubular carcinoma consisting of highly malignant cancer cells with many mitoses. We refer to this type of carcinoma as " chemo-sensitive carcinoma " and compared the histological therapeutic effects of chemo-sensitive and chemo-insensitive carcinomas., Results: 1) Out of 87 patients, 20 cases (23%) showed the histological features of chemo-sensitive carcinomas on pre-therapeutic needle biopsy specimens. The remaining 67 cases (77%) were classified as chemo-insensitive carcinoma. 2) Histologically marked or complete response were observed in 50% (10/20) of chemo-sensitive carcinomas and 10% (7/67) of chemo-insensitive carcinomas (chi(2)=15.33, p=0.0001). Multivariate analysis of chemo-sensitive carcinoma, including HER2, hormone receptor and p53 status, revealed that chemo-sensitive carcinoma had a significant correlation with the histological therapeutic effects (p=0.01119). 3) Pathological complete response (pCR) was achieved in 35% (7/20) of chemo-sensitive carcinomas and 1.5% (1/67)of chemo-insensitive carcinomas (chi(2)=20.71, p<0.0001). Multivariate analysis revealed that chemo-sensitive carcinoma had a significant correlation with pCR (p=0.0091)., Conclusion: The histological features of chemo-sensitive carcinoma were significant predictive factors for chemotherapeutic efficacy.

Purpose: The aim of this retrospective study was to determine and correlate contrast-enhanced areas and multiple internal dark dots and lines on high-resolution magnetic resonance imaging (HR-MRI) with findings in surgical specimens of ductal carcinoma in situ (DCIS) and to evaluate the ability of HR-MRI to detect DCIS lesions and clarify HR-MRI features characteristic of DCIS., Materials and Methods: This study retrospectively reviewed 11 patients diagnosed with DCIS who had undergone HR-MRI. Pathological findings and results of HR-MRI were compared, and causes of periductal enhancements were analyzed., Results: In all patients, HR-MRI using microscopic coils revealed ductally, segmentally, or regionally enhanced areas containing multiple dark dots and lines, representing local enhancement of stroma adjacent to the mammary duct containing DCIS. Neovascularization, infiltration of inflammatory cells, and focal edema occurred in enhanced periductal stroma. Poorly enhanced linear or dot-like structures correlated with dilated mammary ducts displaying necrosis and tumor impaction., Conclusion: DCIS was successfully depicted on HR-MRI using a microscopy coil in all 11 cases. Ductal, segmental, or regional areas of enhancement with multiple dark dots and lines on HR-MRI corresponded to mammary glands containing DCIS with periductal enhancement.

Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used apocrine marker; however, its expression was recently found to decrease in infiltrating, larger, or metastasizing apocrine carcinomas of the breast. In the breast, monoclonal antibody (MAb) B72.3 has been reported to be useful as an apocrine marker although it is used for that purpose much less frequently than GCDFP-15. In the search for a more consistent apocrine marker, immunoreactivity for MAb B72.3 was examined in apocrine carcinomas at different stages and compared with GCDFP-15. 47 of 51 apocrine carcinomas (92%) and 9 of 62 ordinary carcinomas (15%) were MAb B72.3 positive, while 39 of 51 apocrine carcinomas (76%) and 13 of 62 ordinary carcinomas (21%) were GCDFP-15 positive. Thus, both sensitivity and specificity were higher for MAb B72.3. Furthermore, unlike GCDFP-15, MAb B72.3 exhibited positivity irrespective of infiltrating status, tumor size, or metastatic status. There was no correlation between MAb B72.3-immunoreactivity and GCDFP-15-expression. The combined usage of MAb B72.3 with GCDFP-15 was useful to confirm the diagnosis of apocrine carcinoma, especially for advanced tumors, with only two cases being negative for both MAb B72.3 and GCDFP-15. Whether these two cases should be differentiated from ordinary apocrine carcinomas remains to be investigated.

To improve the utility of mammary ductoscopy, we investigated the correlation between endoscopic findings and histologic findings using intraductal biopsy specimens. Seventy-one intraductal biopsy specimens obtained from 63 patients between October 2001 and March 2004 were analyzed retrospectively. All specimens were obtained from monotonous intraductal lesions immediately after observation by mammary ductoscopy and were composed of a pure histologic subtype. With regard to endoscopic findings, color was classified as yellow, red, white, or colorless, and morphology was classified as spherical, lobular, mulberry, or amorphous. The histologic subtype was classified as papillotubular, papillary, degenerated, papillary cancer, solid-type ductal carcinoma in situ (DCIS), or cribriform cancer. The relationship between histologic diagnosis, color, and morphology was investigated. Intraductal biopsy specimens included 25 specimens of carcinoma and 46 specimens of papilloma. There was no significant correlation between color and diagnosis. Fourteen of 25 carcinoma specimens were amorphous, and amorphous morphology was significantly suggestive of malignancy (p < 0.001). Further, cribriform cancer was associated with amorphous morphology and yellow color. Morphology may be a useful endoscopically delineated parameter for differentiating intraductal lesions.

Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive technique that has been shown to coagulate benign and malignant tumors. The purpose of this study was to evaluate MRgFUS safety and effectiveness for the ablation of breast carcinomas., Study Design: Thirty women with biopsy-proved breast cancer underwent MRgFUS treatment. Gadolinium-enhanced MR images were used for treatment planning and posttreatment radiologic assessment of treated tissue, and temperature-sensitive MR images provided real-time treatment monitoring. After MRgFUS, all 30 women underwent wide excision or mastectomy. The extent of thermal ablation was assessed with tumor histology., Results: Treatment was well tolerated, with a minimum of adverse effects, especially when performed under local anesthesia. On pathologic examination, mean (+/-SD) necrosis of the targeted breast tumors was 96.9 +/- 4% (median 100%, range 78% to 100%) of tumor volume. Fifteen (53.5%) of 28 evaluable patients had 100% necrosis of the ablated tumor; only 3 patients (10.7%) had less than 95% necrosis. In 28 (93.3%) patients, 100% of the malignancy was within the treatment field, and 98% and 95% of tumor lay within the treatment field in 2 remaining patients. Retrospective analysis in two patients with residual tumor showed treatment was not delivered to the full recommended area, reaffirming the need for precise localization and the value of contrast-enhanced images for treatment planning., Conclusions: MRgFUS has great potential to become a viable noninvasive replacement for lumpectomy. Additional studies focusing on posttreatment image-based evaluation are needed.

Background: The clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long-term follow-up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group., Methods: Patients (N = 1901)with unilateral breast cancer < or = 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan-Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR., Results: At a median follow-up time of 107 months, the 10-year overall and disease-free survival rates were 83.9% and 77.8%, respectively. The 10-year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10-year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676-5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis., Conclusions: Young age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases., (Copyright 2005 American Cancer Society.)

Background: In Japan, postoperative relapse occurs within five years in 9.2 to 16% of patients whose breast cancers have not metastasized to lymph nodes at the time of initial surgery(node-negative, n0). Attempts to find molecular markers able to classify n0 breast cancers in terms of postoperative prognosis have not been successful., Methods: To identify molecular indicators of prognosis for this type of cancer, we used a cDNA microarray consisting of 25,344 human genes to investigate expression profiles of 12 primary breast cancers from patients whose tumors recurred within five years after surgery(5Y-R) and 12 from patients who survived disease-free for more than five years (5Y-F)., Results: Sets of genes characterizing each group in terms of expression patterns in the tumors were selected by Mann-Whitney and random-permutation tests: these panels included 21 genes expressed highly in 5Y-R tumors than in 5Y-F tumors, and 37 with higher expression in the 5Y-F group than in the 5Y-R group., Conclusions: We established a scoring system to prediction of postoperative prognosis which was 100% accurate as to the actual clinical outcomes of the 24 cases and therefore might be useful for predicting prognosis of n0 breast cancers in a clinical setting. The prognostic score system clearly separated the two groups without any overlap, and accurately predicted prognosis in 6 additional cases. Moreover, the extensive list of tumor-related genes identified in these experiments provides valuable information about progression of breast cancer and suggests potential target molecules for therapy of n0 breast cancers.

Purpose: To assess the presence of invasion in non-palpable breast cancer with microcalcifications., Material and Methods: We investigated 157 patients with non-palpable breast cancer with microcalcifications, who had undergone stereotactic core biopsy or vacuum-assisted breast biopsy and operation at the Cancer Institute Hospital between 1995 and 2001. We investigated the correlation between the area of calcification (maximum range of microcalcifications measured in mm by direct mammography), morphology of calcification on mammography, histological subtype of intraductal carcinoma (comedo or non-comedo) and frequency of invasion, and lymph node metastasis. The chi-square test was used in the statistical analysis and p values less than 0.05 were considered statistically significant., Results: Invasion was observed in 33 of 157 pts (21%), of whom 23 showed minimal invasion, which is less than 0.5 cm in greatest diameter. The risk of invasion was 13% within 10 mm of the microcalcifications (n =70), 25% from 11 to 30 mm (n =59), and 32% more than 31 mm from the microcalcifications (n =28). The risk of invasion was 16% for punctate-round and amorphous type (n =87) microcalcifications, and 27% for pleomorphic and linear-branching types (n =70)(p =0.092). In addition, invasion was found 10% of the time within 10 mm of punctate-round and amorphous type microcalcifications, and 20% of the time at 11 mm or more. On the other hand, invasion was found 15% of the time within 10 mm of pleomorphic and linear-branching type microcalcifications, and 37% of the time at 11 mm or more. In 72 cases of intraductal carcinoma diagnosed by pathological examination, invasion was found in 10 of 31 (32%) comedo type intraductal carcinomas and in 5 of 41 (12%) non-comedo types (p =0.0379). There were 5 cases (3.2%) with axillary lymph node metastasis, all of which widely extended more than 21 mm from the microcalcifications., Conclusion: The risk of invasion was 10% within 10 mm of punctate-round and amorphous type microcalcifications, and 37% at more than 11 mm of pleomorphic, linear-branching microcalcifications.

We began performing breast-conserving surgery (BCS) in 1986 to achieve complete resection of breast cancer and omit postoperative radiotherapy (RT) if serial and detailed pathologic examination of the resected specimen within a 5-mm width showed that the of margin was cancer free. At of the end of 1998, 1,233 sides of the breast had been conserved, of which 827 sides were shown to have cancer-free margins. As of the end of 2001, with a mean observation period of 79 months, ipsilateral breast tumor recurrence was recognized on 46 sides (19 recurrences, 27 multiple cancers), for a recurrence rate 5.6% and an annual recurrence rate of 0.85%. This rate is slightly better than those reported by eminent institutions in the USA and Europe which all perform RT, confirming the accuracy and safety of our BCS.

Background: To diagnose intraductal lesions endoscopically the Japanese Association of Mammary Ductoscopy classified the endoscopical appearance of lesions into three types. We investigated the correlation between endoscopic classification and histological diagnosis., Methods: From April 1998 to February 2001, we enrolled 129 female patients who were diagnosed histologically and whose intraductal lesions were detected by mammary ductoscopy. The endoscopic classification consists of three types. The polypoid type is a localized expansive lesion. This type is divided into two subtypes, the solitary subtype (solitary polypoid lesion) and the multiple subtype (multiple polypoid lesions). The combined type is polypoid lesion(s)coexisting with a superficial type. The superficial type is a superficial spreading lesion such as a continuous luminal irregularity accompanied by no obvious elevations., Results: There were 65 cases of breast cancer and 64 cases of benign papillary lesions. Fifty-four cases of benign papillary lesions and 7 cases of breast cancer were classified as the polypoid-solitary type. Seven benign cases and 13 cases of cancer were classified as the polypoid-multiple type. Two benign cases and 16 cases of cancer were classified as the combined type. Only one benign case and 29 cases of cancer were classified as the superficial type. There is significant correlation between endoscopical types and the histological diagnosis (p<0.0001)., Conclusions: Endoscopic classification is useful to diagnose intraductal lesions.

Purpose: To compare three-dimensional (3D) helical CT with 3D MRI in the evaluation of intraductal spread of breast cancer., Methods: Fifty patients with breast cancer were examined. Tumor size ranged from Tis to T2. The whole breast was scanned by both breath-holding helical CT and MRI with contrast media. Linear or segmental enhancement, and spotty enhancement around the main tumor were considered to indicate ductal carcinoma in situ (DCIS) or ductal spread. These findings were compared with thin section histopathologic data., Results: Seventeen of 35 patients had intraductal spread with invasive cancer and 15 patients had DCIS. The sensitivity, specificity, and accuracy of 3D CT in detecting intraductal spread or DCIS were 71.9%, 83.3%, and 76.0%, respectively, and those of 3D MRI were 87.5%, 61.1%, and 78.0%. Overestimations numbered three (6.0%) on CT and seven (14.0%) on MRI, and underestimations numbered nine (18.0%) on CT and four (8.0%) on MRI., Conclusion: 3D helical CT can provide good information about the spread of breast cancer and could be an alternative to 3D MRI for preoperative examination of breast cancer.

Background: Fluorescent in situ hybridization (FISH) has been shown to be one of the most reliable methods with which to estimate the status of the HER-2/neu (or c-erb B-2) oncogene at the DNA level., Methods: To study interobserver reproducibility and to determine more clinically correlated criteria for HER-2/neu alterations, two observers independently estimated HER-2/neu DNA status. The correlation between the consensus HER-2/neu DNA status by FISH and HER-2/neu protein status detected by immunohistochemistry (IHC) using a polyclonal antibody was studied in 216 surgically resected breast carcinomas and 34 noncancerous tissues., Results: According to the HER-2/CEP17 ratio and mean HER-2 copies per nucleus, agreement level of HER-2/neu amplification was shown to be nearly perfect between two observers (kappa statistic (kappa) = 0.94 and kappa = 0.84). Finally, 40 tumors (19%) were judged to have HER-2/neu DNA amplification, with 6 having low-level amplification (> or = 2 but < 3 folds) and 34 having high-level amplification (> or = 3 folds). One hundred seventy-six other tumors, including 3 tumors that only 1 of the observers determined to be low-level amplifiers, and 34 noncancerous tissues had no detected amplification. The DNA amplification status was concordant between invasive and intraductal components in 14 carcinomas. HER-2/neu protein overexpression of moderate (2+) or high (3+) intensity based on IHC was detected in 51 carcinomas (24%), and was 2+ in 20 carcinomas and 3+ in 31 carcinomas. The HER-2/CEP17 ratio of > or = 2 was concordant with IHC findings of 2+/3+ in 91% of carcinomas (195 of 215 carcinomas), with a sensitivity of 70% (35 of 50 carcinomas) and a specificity of 97% (160 of 165 carcinomas). High-level amplification was detected in 29 of 31 IHC 3+ cases (94%), but in only 5 of 20 IHC 2+ cases (25%) and 0 in 165 IHC 0/1+ cases. All 34 cases with high-level amplification showed an IHC score of 3+ (29 cases) or an IHC score of 2+ (5 cases), but only 1 case was found to have an IHC score of 3+ and the remainder were IHC 0/1+ in 6 low-amplification cases. The concordance rate of the high-level amplification with an IHC score of 3+ was 97% (208 of 215 cases), with a sensitivity of 94% (29 of 31 cases) and a specificity of 97% (179 of 184 cases)., Conclusions: The results of the current study indicated that high-level HER-2/neu amplification and an IHC score of 3+ nearly optimally identified breast carcinomas with clinically and biologically significant HER-2/neu activation. Conversely, it was confirmed that careful interpretation of test results is required in the case of low-level amplification and/or an IHC score of 2+., (Copyright 2001 American Cancer Society.)

Background and Objectives: The UICC and the Japanese Breast Cancer Society have different TNM classifications. There is a large discrepancy between the pathological node status in the UICC (UICC-NS) and JBCS (JBCS-NS) systems. We compared the UICC-NS with the JBCS-NS., Methods: Reviewed were data on 1,684 invasive ductal carcinomas at the Cancer Institute Hospital from 1981 to 1986. Each case was categorized according to the UICC-NS and JBCS-NS, respectively. Overall survival 10 years after surgery (OS) by UICC-NS and JBCS-NS was calculated by the Kaplan-Meier method., Results: OS with UICC-NS and number of case were, respectively, 87.8% and 968 for pN0, 83.9% and 93 for pN1a, 71.6% and 190 for pN1bi, 60.0% and 25 for pN2, 58.8% and 51 for pN1bii, 55.7% and 238 for pN1biii, 54.2% and 24 for pN1biv, 44.8% and 58 for pN3, and 20.6% and 34 for pM (LYM). Differences between pN1a and pN1bi and pN3 and pM (LYM) were significant (p < 0.05). In JBCS-NS, they were 87.8% and 968 for n0, 75.3% and 384 for n1 alpha, 51.3% and 152 for n1 beta, 46.6% and 141 for n2, 21.2% and 33 for n3, 0% and 2 for n4d and n4i, respectively. Differences between n0 and n1 alpha, n1 alpha and n1 beta, and n2 and n3 were significant (p < 0.05)., Conclusions: With a large number of classification factors, UICC-NS was more complicated and hard to show significant difference in OS than JBCS-NS. But the latter also had redundant classifications. So, it is necessary to establish a new, simple, and easy-to-register node classification in future., (Copyright 2001 Wiley-Liss, Inc.)

A quantitative model was devised for the purpose of evaluating interobserver agreement in the judgment of the nuclear atypia score of cancer cells in protocol studies. In this model, the mean nuclear atypia score (mu) among observers was considered to approximate the 'true' nuclear atypia score of the tumor, and with an identical mu the strength of interobserver agreement was evaluated by the difference between the ideal standard deviation (sigma) and the observed sigma in the slide conference session. This model was applied to the data of a total of 216 invasive ductal carcinomas acquired at eight slide conference sessions held for the standardization of nuclear atypia scoring and monitoring of interobserver agreement level for enrolled cases in a surgical adjuvant protocol on breast cancer. Compared with conventional percentage interobserver agreement and kappa statistics, the present model, named the lambda model, was more sensitive in detecting the improvement of interobserver agreement in nuclear atypia scoring with repetition of slide conference sessions. The lambda model was particularly effective for evaluating the session which included many intermediate cases with a score between 1 and 2 or between 2 and 3. Percentage interobserver agreement and kappa statistics could estimate the agreement irrespective of the number of observers, but the agreement tended to be underestimated when these intermediate cases were in the majority. The present method was considered to be complementary to conventional methods for evaluating interobserver agreement of cancer histology in protocol studies.

Background: As the incidence of ductal carcinoma in situ (DCIS) is increasing, it is necessary to make a guideline for the pathological examination and diagnosis of DCIS, by creating criteria based on clinical and biological aspects of the disease., Method: We collected biopsy specimens originally diagnosed as benign lesions, from patients who subsequently developed invasive carcinoma in the ipsilateral breast. The histology of the biopsy specimens was re-evaluated principally according to the 1995 Philadelphia Consensus on DCIS. Histopathological agreement on each biopsy specimen was made by the JBCS Study Group members under a multiviewer microscope. In the course of making conclusive agreements among the pathologists, we developed a consensus for the histopathological diagnosis of DCIS, especially non-comedo types., Results: DCIS is defined as a carcinoma of ductal epithelial origin, without any evidence of stromal invasion. It is necessary to note the methods of pathologic examination required to diagnose DCIS. Stromal invasion is an important prognostic factor, and should be diagnosed with caution. Classification of proliferative ductal lesions as benign or malignant (DCIS), the subtype of DCIS (nuclear grade, architecture, and necrosis), and the histological grading of DCIS are proposed and recommended., Conclusion: Although we have made a new proposal according to current concepts, there are still several unresolved problems. Thus further examination and modification will be necessary in the future.

Background: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo., Methods: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998., Results: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5%, Conclusions: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.

Background: A multi-institutional randomized clinical trial of adjuvant therapy for patients with high-risk node-negative (n0) breast cancer has been undertaken in Japan. The pathology panel was organized in order to establish histological criteria to identify patient groups with higher rates of recurrence., Methods: Initially, three pathologists independently judged the nuclear grade, composed of nuclear atypia and mitotic counts, of 100 n0 invasive ductal carcinomas, focusing on interobserver variation of the nuclear grade and its correlation with patient prognosis. These pathologists then gave consensus histological types and nuclear grades for 130 other n0 breast carcinomas and examined the prognostic significance of the grade., Results: In the first study, nuclear grade 2-3 significantly identified a patient group with a rate of recurrence of 17-20% by any pathologists and the degree of agreement for the grade was fair. In the second study, the consensus type and nuclear grade identified a group (n = 66) with a 22% recurrence rate and another group (n = 64) with a 3.6% recurrence rate at 10 years. In 12 tumors, the resection-fixation interval of the tumor did not generate any significant difference in mitotic counts., Conclusions: The histological type and the nuclear grade clearly identified a higher-risk patient group with n0 breast carcinoma, and may be applied to the multi-institutional protocol study when the criteria have been well standardized by the pathologists.

Detection of small or early neoplastic lesions is essential for the secondary prevention of cancer, and for this purpose information concerning their incidence and characteristics is required. Although data for latent or early cancers are available for various organs, details are limited in the case of the breast. The present investigation was carried out to cast light on the incidence of latent cancers, considered as lesions, in women with no symptoms and no palpable mass of the breast. Out of 2126 women visiting our hospital for initial breast examination during July to December in 1987, 542 (25.5%) had no complaint and neither a detectable mass on careful palpation nor a tumor shadow on mammography. However, 21 (3.9%) demonstrated microcalcification, 7 giving the impression of a possible malignancy. Subsequent biopsy of the 7 cases revealed 3 carcinomas. The detection rate of breast cancer in this population was thus 0.6% (3/542). Adopting the frequency (36%) of microcalcification detectable on mammography in 185 breast cancers diagnosed in this period as a base, the incidence of latent breast cancer among women visiting our hospital was calculated to be 1.5%.