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IgG4-related disease is a newly identified disease entity that has begun to attract attention, and international consensus diagnostic criteria for the condition have recently been proposed. The characteristic features of IgG4-related disease are lymphoplasmacytic infiltration involving a high proportion of IgG4-positive cells, fibrosis exhibiting a storiform pattern, and obliterative phlebitis. It can affect various organs, including the breast (in rare cases). IgG4-related disease has previously been referred to as inflammatory myofibroblastic tumor, plasma cell granuloma, or pseudolymphoma. We have experienced a case of IgG-related disease of the breast. Clinically and cytologically, the lesion was somewhat similar to a malignant tumor. An immunohistochemical examination of a core needle biopsy sample resulted in a correct diagnosis. In addition, a review of the patient’s clinical history revealed that the disease had affected areas other than the breast. Clinicians should be aware that breast lesions can be a focal manifestation of systemic disease, and overdiagnosis should be avoided by performing appropriate pathological analysis.

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.

Since the concept of gene profile-based intrinsic subtypes was proposed, various studies on pathological characteristics have been performed. Particularly, triplenegative (TN) breast cancer, which is negative for all hormone receptors [estrogen receptor (ER) and/or progesterone receptor (PgR) and human epidermal growth factor 2 (HER2)], has been attracting attention because effects of endocrine and targeting therapies cannot be anticipated and thus selecting a treatment method is difficult. TN cancer accounts for about 10%-15% of all invasive breast cancer cases in Japanese, which is significantly lower than the incidence reported in the United States. Cytokeratin (CK) 5/6 or epidermal growth factor receptor (EGFR) is positive in 80%, being classified as basal-like carcinoma, but it should be understood that TN breast cancer and basal-like carcinoma are not necessarily the same. Criteria for positivity judgment of ER, PgR, and HER2 were established to select treatment in cases positive for each marker, and greater importance is attached to strict accuracy control. Inversely, the level of negative findings to judge TN varies among the judgment criteria. In any case, the prognosis of TN breast cancer is poor. Pathologically, TN breast cancer shows certain morphological characteristics, such as high grade and a pushing margin, and abnormalities of BRCA1 and p53 are frequently noted. At present, as no effective therapeutic strategy has been established for TN breast cancer, further clarification of the molecular biological characteristics of such cancers is needed. In addition, the incidence of TN-type ductal carcinoma in situ (DCIS) is low, suggesting that TN does not remain preinvasive DCIS for a prolonged period and that it transforms to invasive cancer in an early stage. Because mammary gland basal cells have characters of progenitor or stem cells that differentiate into both luminal epithelium and myoepithelial cells, these cells may be utilized for the differential diagnosis of the benignity or malignancy of intraductal lesions in routine pathological practice. As proliferation markers, such as Ki-67, and multiple gene arrays for gene signature are also utilized to select adjuvant therapy, analysis may progress further in the future.

Aromatase inhibitors (AIs) have been employed as adjuvant therapy or as treatment for recurrent cases. However, when AI treatment fails, it is unclear which endocrine therapy is the most appropriate to introduce at this point and how effective it will be. In this study, we investigated the efficacy and safety of toremifene (TOR, Fareston(®)), a selective estrogen receptor modulator (SERM).Patients with recurrent or advanced breast cancer who had measurable or evaluable lesions, and were diagnosed as having progressive disease during AI treatment and subsequently given TOR at 120 mg/day (TOR120) as endocrine therapy were selected and analyzed retrospectively in relation to their medical history.Of a total of 83 cases examined, 80 were evaluable. The objective response rate (ORR) was 15.0% (12/80), the clinical benefit (CB) rate was 45.0% (36/80), and median time to failure (TTF) was 7.8 months. TOR120 was also effective in the progressive disease cases relapsed on AI treatment. When TOR120 was used, as a first-, second- or third-line treatment, the CB rate was 57% (32/56); this fell to 17% (4/24) when TOR120 was used as a fourth-line or later treatment. There was no response in the five estrogen receptor (ER)-negative cases, compared with an ORR of 15% (10/67) in ER-positive cases. In cases with a human epidermal growth factor receptor 2 (HER2) score of 0, 1+, and 2+, the ORR was 11% (7/61), while there was no response in the five cases with scores of 3+. TOR120 was effective in cases previously treated with tamoxifen (TAM), with an ORR and CB rate of 12 and 29%, respectively. The last AI used was anastrozole in 30 cases and examestane in 46; the response rates to TOR120 were similar in both groups. With regard to adverse effects, hot flushes and/or night sweating was observed in 10 and 12 cases, respectively, but all of them were categorized as grade 1, and the treatment was rated excellent in acceptability.TOR120 was rated excellent in acceptability, and high efficacy was observed when it was used up to third-line treatment for AI-failure cases, although this study may show some selection bias because of the retrospective study. In addition, it was also considered effective for TAM-failure cases.

Background Sentinel node biopsy is emerging as a technique to replace routine axillary lymph node dissection. The lymphatic mapping technique is still at a developmental stage and no standard technique exists. This study used technetium-99m colloidal rhenium sulphide with a mean particle size of 100 (range 50–200) nm for sentinel node mapping. Methods Eighty-seven patients with breast cancer, but no clinical evidence of axillary metastasis, were studied. One day before operation technetium-99m colloidal rhenium sulphide was injected at four points into breast tissue surrounding the tumour. Lymphoscintigraphy was performed 2 h after injection, and surgery was usually performed after 20 h. A hand-held γ probe guided sentinel node biopsy. Results Lymphoscintigraphy revealed axillary hot spots in all patients. During operation, the sentinel node was identified in all 87 patients (100 per cent). The number of sentinel nodes per patient ranged from 1 to 5 (mean 2). Metastatic sentinel nodes were identified in 37 of 87 patients. There were no false negatives. Conclusion This study suggests that technetium-99m rhenium sulphide is a suitable agent for sentinel node mapping in patients with breast cancer.

The effect of age on the prognosis of breast cancer remains controversial. To investigate the role of age, we reviewed 316 patients with stage I or II breast cancer. There were 14 patients below 34, 146 between 35 and 49, 115 between 50 and 65, and 41 over 66 years of age. No correlations were observed between age and clinicopathological variables. Breast cancer patients aged 34 or less had a significantly worse survival compared to those in the older age groups. Multivariate analysis also showed younger age to be a significant factor, followed by lymph node status. Therefore, younger age at onset is considered to be an independent prognostic factor.

With the growing use of mammography for routine breast cancer screening, tumors are now detected earlier and more frequently than ever before. Consequently, it is becoming increasingly important to define the exact location of early lesions to allow effective treatment through precision surgery. The most common form of noninvasive breast cancer— ductal carcinoma in situ (DCIS)—is not generally noticed as a palpable tumor but as calcification during breast screening with mammography. DCIS generally does not metastasize, and thus, localized surgery and radiotherapy can be used to treat this lesion, thereby sparing most of the unaffected breast tissue. More invasive lesions, however, such as invasive ductal carcinoma (IDC), also require complete resection, including a margin of unaffected tissue, to ensure complete removal. The situation is complicated by the coexistence of an intraductal component with IDC. If this intraductal lesion is missed during imaging when IDC is present, it may not be removed by subsequent surgery and can thus give rise to a positive surgical margin, increasing the likelihood of recurrence. In this special feature, authors present a review of each imaging modality together with results of their own recent studies aimed at overcoming the limitations associated with the diagnosis of intraductal component coexisting with IDC and DCIS. Among the imaging tests considered is mammography, a routine screening methodology for breast cancer, which can detect DCIS primarily by identifying microcalcification. This calcification is also useful for confirming the complete resection of lesions by specimen radiography, especially in breast-conserving surgery. However, only half of DCIS lesions are associated with calcification, and even if the lesion does contain calcification, the gland can become deformed by compression during the procedure, making it difficult to identify the exact site of calcification in surgery. Ultrasound examination is another commonly used imaging modality. Although it is considered to have poor reproducibility, it has high sensitivity and resolution for minute lesions, and the location of the lesion is easily projected onto the overlying skin. However, some DCIS lesions, without dilation of the duct, are missed by this diagnostic modality. In this edition, Nakajima et al. present results using B-mode, Doppler, and elastography for predicting intraductal components. Magnetic resonance imaging (MRI) is now considered the most sensitive method for detecting DCIS lesions. Its ability to image without radiation exposure is a great advantage over computed tomography (CT). MRI is thus more frequently used to identify early lesions in case of suspicious findings during physical examinations or other diagnostic imaging examinations. Tozaki et al. review the use of MRI for the detection of DCIS lesions, including the new Breast Imaging-Reporting and Data System (BI-RADS) terminology for MRI. Of particular note is the patient’s prone position during the scan, which limits application of MRI in surgery. Thus, if the lesion has a feature that could be detected by sonography, its combination with MRI could be a significant advantage in identifying the precise location and area of the lesion. Computed tomography is another effective imaging test for breast cancer. It is mainly used as a modality for staging of breast cancer, and it is not considered as the best I. Kimijima (&) Northern Fukushima Medical Center, Breast Center, Fukushima, Japan e-mail: kimijima0505@live.jp

Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen.The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events.A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated.Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.

As ductal carcinoma in situ (DCIS) lesions can spread widely in the ductal-lobular segment, often without palpable tumor, complete resection of the lesion in breast-conserving surgery requires establishment of the precise location and extent of the lesion during preoperative imaging studies. We investigated the potential of multi-detector row computed tomography (MDCT) in detecting and delineating DCIS lesions. Overall, 74 patients with 75 DCIS lesions underwent breast MDCT. The size of the DCIS lesion in each patient was measured in the volume rendering images and compared to the size obtained by pathological mapping. The differences between the actual tumor size and that obtained from MDCT (L-Path and L-CT) were calculated, and the relationships between these differences and tumor characteristics were investigated. DCIS was detected fully or partially in 64 (84.9 %) of 75 lesions, whereas the detection rate of magnetic resonance imaging (MRI) was 90 %. The detection rate was not influenced by comedo/non-comedo status, but the detection rate of higher nuclear grade DCIS lesions tended to be higher than that of low grade lesions (p = 0.089), while the estimated size was also more accurate in the former (p = 0.046). Hormone receptor and Her2 status did not affect MDCT findings. MDCT is highly effective for detecting DCIS, especially the more aggressive types of DCIS. Moreover, the patient’s position during MDCT imaging is more similar to that during surgery than that during MRI, making MDCT a highly useful presurgical imaging technique for the assessment of DCIS.

乳癌における核形態と臨床病理学的諸因子との関連を検討した.原発乳癌90例および乳腺良性疾患13例を対象とした.May-Grunwald-Giemsa染色の細胞診標本を用いて約200個の核について核面積および核最大長径を画像解析装置を用いて計測した.核面積は乳腺良性疾患に比べて乳癌が有意に大きかった (P=0.00001).乳癌と臨床病理学的因子との検討では, 腫瘍径が大きくなるにつれて核面積も有意に大きくなっていた (P

The relation of the endocrinological factors to estrogen receptor (ER) status is still unclear. In this paper the effect of hypophyseal gonadotropins on ER status was studied in 40 postmenopausal patients with breast cancer. The plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels before and after luteinizing hormone-releasing hormone (LH-RH) stimulation at an i. v. dose of 100μg were measured time-depedently. ER in the tumor was measured by dextran-coated charcoal methods. Twenty-three out of the 40 patients were ER positive, 17 being negative. The basal levels of LH and FSH were 98.7±45.5 mIU/ml and 105.5±51.2 mIU/ml in ER positive patients, and were 91.4±31.4 mIU/ml and 87.5±32.6 mIU/ml in ER negatives, respectively. There was no significant difference in basal LH and FSH between ER-positive and negative patients. No ER-relating time-dependent pattern in LH and FSH levels was found. Responses after LH-RH stimulation were not different between two groups. In conclusion, hypophyseal gonadotropin levels and its reserves as host factors were not related with ER status in the postmenopausal patients with breast cancer.

A case of synchronous triple cancer which involved the tongue, breast and esophagus was experienced. A 58-year-old woman underwent right partial resection of the tongue with a diagnosis of tongue cancer. This was in stage I showing the histological feature of well-differentiated squamous cell carcinoma. The second neoplasm, a right breast cancer, was diagnosed about two months after the first operation. A modified radical mastectomy was done (stage II), and the solid tubular carcinoma was histologically revealed. Around 4 months after the second operation for breast cancer, poor appetite and a gradual body weight loss occurred, and then 3 months later, an esophageal cancer was detected. Biopsy specimen revealed moderately differentiated squamous cell carcinoma in an advanced stage. It was inoperable. Systemic chemotherapy failed to cure and the patient died 6 months later. In this paper clinical course as well as flow cytometric DNA analysis of this synchronous triple cancer which was performed by using these paraffin-embedded tissues is described. Triple carcinomas seen in the literature are also discussed.

Upon performing contact thermography on the patients with breast cancer, the thermograms obtained were classified into 3 types (hot spot: H, irregular vascular pattern: IV, and asymmetrical thermal pattern: AT). The following results have been obtained as a result of making an assessment regarding how the findings are reflected on the classification of clinically morbid periods.1) Positive AT and IV findings were observed on the thermograms even in the breast cancers in comparatively early stages.2) H findings showed that the positive rate became higher as tumorous diameter became larger and further that high positive rates were exhibited in scirrhus carcinoma.3) In the relation with nuclear DNA amount, positive rates of H findings were high in aneuploid cases.4) The change in thermography showed a positive correlation with the change in dermal blood stream.From the above, it was found that the contact thermography has a nature a little different from the conventional test methods and that its usefulness was observed rather in the judgement on the malignancy of breast cancer cells but not as diagnostic test method. Further, a possibility of foreknowing the risk of breast cancer to occur was suggested.

To compare the cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and the anthracycline-containing regimen cyclophosphamide, epirubicin, and fluorouracil (CEF) to evaluate the efficacy and safety of the latter.A total of 294 patients with axillary node-positive primary breast cancer of STAGE I-IIIa were randomly assigned to either CEF [cyclophosphamide (CPA) 500 mg/m(2) i.v. days 1 and 8; epirubicin (EPI) 60 mg/m(2) i.v. day 1; and 5-fluorouracil (5-FU) 500 mg/m(2) i.v. days 1 and 8] or CMF [CPA 500 mg/m(2) i.v. days 1 and 8; methotrexate (MTX) 40 mg/m(2) i.v. days 1 and 8; and 5-FU 500 mg/m(2) i.v. days 1 and 8]. Both treatment regimens were comprised of six cycles at 4-week intervals. Tamoxifen (TAM) 20 mg/day was concomitantly given to estrogen receptor (ER)-positive patients and those with undetermined ER status for 2 years.The overall 5-year survival was 77.1% for CEF and 71.4% for CMF [p = 0.24; hazard ratio 0.79 (95% CI 0.50-1.24)], and the 5-year disease-free survival was 55.7% for CEF and 48.9% for CMF [p = 0.15; hazard ratio 0.80 (95% CI 0.57-1.12)]. Although the log-rank test did not show a significant difference, both overall and disease-free survivals were higher for CEF according to the point estimates. Adverse drug reactions (ADRs) occurred more frequently in CEF.Whereas CEF had a good trend compare with CMF, it could not be proven statistically significant. The principal cause of the failure seems to be insufficient power, that is, the dose intensity (EPI: 60 mg/m(2)) set 10 years ago, when the trial began, was low, and the number of trial subjects was small because of the background of the times, which made the accumulation of cases extremely difficult. However, the trial should be considered to be meaningful, as it was the first, formally conducted controlled trial on chemotherapy in Japan.

Purpose: We compared the therapeutic usefulness of doxifluridine (5′-DFUR) alone and a combination of 5′-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. Patients and Methods: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5′-DFUR alone or 5′-DFUR plus CPM. All patients initially received 5′-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5′-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5′-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5′-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. Results: Of the 1,088 eligible women, 546 were assigned to receive 5′-DFUR alone and 542 were assigned to receive 5′-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5′-DFUR plus CPM than in those who received 5′-DFUR alone (log-rank test, P = .021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5′-DFUR group and 32.3% of patients (175 of 542) in the 5′-DFUR plus CPM group (χ2 test, P < .001). Conclusion: Combination therapy with 5′-DFUR plus CPM is more effective in preventing recurrence than 5′-DFUR alone.

To assess the efficacy of 5'-DFUR, an intermediate of capecitabine, for adjuvant treatment of early breast cancer, we conducted an open-labeled multi-center randomized controlled trial to compare postoperative 5'-DFUR treatment with surgery alone. We enrolled 1217 primary breast cancer patients and randomly assigned them into two treatment groups; one received six-month postoperative 5'-DFUR treatment by consecutive or intermittent administration, and the other surgery alone. Follow-up surveys were conducted once a year for all subjects simultaneously and examined their outcome/presence or absence of the cancer recurrence. The central study committee reviewed all follow-up data and judged the recurrence data to be used for the analysis. Eight-year follow-up data showed no significant differences in relapse-free and overall survival between the two groups, and 5'-DFUR treatment regimen showed an extremely high tolerance. Possible explanations are discussed for the finding of no significant survival difference between adjuvant 6-month 5'-DFUR monotherapy and surgery alone in early breast cancer.

Background To assess whether lymph nodes are consistently negative below a certain tumor size, we investigated the incidence and predictors of lymph node metastasis in breast cancer patients with tumors under 2 cm in size.

BACKGROUND: Prognostic factors for predicting the recurrence of node-negativebreast cancers have been controversial. The present study was performed to elucidate practically useful prognostic factors using formalin-fixed paraffin sections. METHODS: This was a case-controlled multi-institutional study that composed 40 patients with recurrent node-negative breast cancer and 80 patients with node-negative breast cancer but without recurrence after radical surgery. Tumors weresmaller than 3 cm in diameter and were treated surgically between January 1, 1985 and December 31, 1990. The recurrent and non-recurrent cases were matched with regard to their age, adjuvant chemotherapy and the year in which surgery was performed. Fourteen immunohistochemical factors and 8 histological factors of theprimary tumor were studied on formalin-fixed, paraffin-embedded sections by immunohistochemical and histochemical analyses. RESULTS: According to univariate analysis, factors such as progesterone receptor (PgR), MIB-1, CD44v6, CD44v9 and platelet-derived endothelial cell growth factor (PDECGF) were significantly different between the recurrent and non-recurrent groups (ply; 0.1; Wilcoxon-Mann-Whitney analysis). Chi-squared test showed significant differences in MIB-1, cdc2 and stromal plasminogen activator receptor (suPAR). Histologically, mitotic count was also significantly different between the two groups (p0.005). Multivariate analysis revealed that positivity for cdc2 (p=0.01), high mitotic count (p=0.04) and negativity for CD44v9 (p=0.02)were independent prognostic factors among variables selected by univariate analysis, and that positivity for MIB-1 (p=0.03) and cdc2 (p =0.01), and negativity for CD44v9 (p =0.03) were independent prognostic factors among the immunohistochemical markers examined. CONCLUSION: Our results indicated that positivity for MIB-1 and cdc2, high mitotic count and negativity for CD44v9 could serve as independent factors for predicting the recurrence of node-negative breast cancer.

BACKGROUND: Recently objective quantification of immunohistochemical estrogenreceptor (ER) and progesterone receptor (PgR) staining in breast cancer by image cytometry has been predominantly performed by measuring the area of positivelystained cells. However, in sample preparations of immunostained hormone receptors, both the stained area and the intensity of staining vary. In this study, we performed quantification of the stained area by measuring, tailing intensity using image cytometry. METHODS: Quantitative analysis of ER and PgR immunohistochemistry was performed using image cytometry. The obtained values were presented as % of positive staining (% PS). Comparison of % PS with values obtained by EIA and with clinicopathological features was performed. RESULTS: The % PS values and the natural logarithm of the EIA levels of the hormone receptors showed a significant positive correlation for both ER and PgR. The concordance of the results obtained by the two methods was 96.3% for ER and 73.7% for PgR. The ER-% PS values of postmenopausal patients were significantly higher than those of premenopausal patients, whereas the PgR-% PS values of the former group were significantly lower than those of the latter group. CONCLUSION: The quantification of ER and PgR in immunostained preparations using % PS as a parameter was reproducible and showed a high correlation with values obtained by EIA. It was shown that only menopausal status affects hormone receptor levels when analyzing the relationship between % PS measurements and clinicopathological features.

BACKGROUND: Abnormal glycosylation patterns have been recognized as a featureof carcinomaassociated mucins. The expression of the Tn antigen in breast cancer tissue was investigated to assess its prognostic relevance. METHODS: Formalin-fixed, paraffin-embedded materials from 219 patients with breast cancer were used. Immunohistochemical staining of the Tn antigen was retrospectively investigated and a lesion staining 10% or more was considered positive RESULTS: Tn antigen expression was present in 99 (45%) of 219 lesions. There were no correlations between Tn antigen expression and mean patient age, nodal status, estrogen receptor status, or menopausal status, but there was a slightly significant association between Tn and tumor size. Patients negative for the Tn antigen had a significantly better survival rate than those who were positive. Multivariate analysis also indicated that Tn expression correlated significantly with overall survival in addition to nodal status and tumor size. CONCLUSION: Tn expression was a significant prognostic factor in breast cancer, but the significance was lost on multivariate analysis. The biological implication of Tn expression in breast cancer needs further investigation.

Loss of heterozygosity (LOH) on chromosome 6q is often observed in breast cancer, suggesting the existence of a putative tumor suppressor. Recently, a human homolog of the Drosophila warts tumor suppressor gene, h-warts/LATS1, was identified and mapped at chromosome 6q24-25.1. Mutation analysis of the h-warts/LATS1 was performed using 25 breast cancer tissues by RT-PCR SSCP analysis. Although LOH of the h-warts/LATS1 was found in one patient, no mutations were found. Two polymorphisms were found, but neither of them caused amino acid substitutions. Further investigations are necessary to elucidate the role of the h-warts/LATS1 gene in the carcinogenesis of breast cancer.

Adenoid cystic carcinoma of the breast is an uncommon form of cancer, and only a few articles have described the cytological findings of this disease. We report herein the case of a 48-year-old woman who presented with a breast mass beneath the nipple, the aspirate from which consisted of globules of mucous balls surrounded by epithelial cells with scant cytoplasm and hyperchromatic nuclei. Microscopically, the tumor was formed by myoepithelial cells and glandular epithelial cells in a biphasic pattern. Immunohistochemical study revealed positivity for smooth muscle actin. A left total mastectomy with axillary lymph node dissection was performed. None of the 22 axillary lymph nodes contained metastases, and the patient remains well and free from recurrence 29 months after her operation. This case report provides some information about the cytological diagnosis and the accuracy of fine-needle aspiration, which must be considered despite the rarity of this disease.

Fatty acid synthase (FAS) is the key enzyme required for the conversion of dietary carbohydrates to fatty acids. Recent studies have demonstrated that high levels of FAS expression occur in a variety of cancers, including breast cancer. We evaluated 243 primary breast cancer patients in the period between 1989 and 1996. Immunohistochemical staining for FAS was performed on formaline-fixed, paraffin-embedded sections. FAS staining intensity was graded as low or high. The expression of FAS was high in 145 (60%) and low in 98 cases (40%). A weak correlation between FAS expression and nodal status was noted in premenopausal patients (p=0. 01). FAS was associated with estrogen receptor (p=0.0022) and progesterone receptor (p=0.0085) status. We found that a low expression of FAS was significantly related to a shorter disease-free survival (DFS) rate in estrogen receptor positive patients (p=0.024) and a similar trend was recognized in progesterone receptor positive patients (p=0.083). The low FAS group showed better DFS and OS in all but ER-/PgR- cases (p=0.011, 0.076). This study showed close correlations between immunohistochemical FAS expression and steroid hormone receptors in premenopausal patients. The use of FAS expression may increase the diagnostic utility of ER and PgR in premenopausal patients. FAS may be able to predict the responsiveness of tumors to endocrine therapy.

The proto-oncogene bcl-2 is demonstrated to block a final common pathway leading to apoptosis and is expressed in more than half of human breast cancers. Invasive breast cancer has reduced bcl-2 immunostaining compared with normal breast epithelia and preinvasive breast lesions. As an inhibitor of apoptosis, bcl-2 should correlate with highly aggressive tumor biology and resistance to hormonal/cytotoxic therapy. However, high bcl-2 expression has been shown to associate with a number of favorable prognostic factors including ER positivity, PgR positivity, low histological grade, well-differentiated tumor, absence of c-erbB-2 and p53. Unexpectedly, numerous studies have shown that tumors with high bcl-2 expression are more responsive to hormone therapy and have more favorable disease-free and overall survival. The clinical significance of bcl-2 in tumorigenesis and prognosis of breast carcinomas from the data recently published are reviewed. Its role in modulation of hormonal/cytotoxic therapy and future directions are also discussed.

The lymph node micrometastasis was retrospectively immunohistochemically investigated in 185 patients with node-negative breast cancer and compared with the routine conventional findings. The monoclonal antibodies to epithelial membrane antigen (EMA) and mucinous-like carcinoma antigen (MCA) were used. Of 19 EMA-positive cases, 16 were false positive. Therefore only 3 cases were found to show staining with both EMA and MCA. The patients are all living and well and free of recurrence. No micrometastasis was immunhistochemically demonstrated in 11 node-negative breast cancer patients with subsequent metastases. The results of the present study indicate that the detection rate containing occult cells afforded by conventional routine evaluation is sufficient, at least in Japanese.

Mutations in the p53 gene were analysed in 50 cases with breast cancer by PCR-SSCP and direct DNA sequencing. Mutations were found in 10 of 50 cases (20%) including a case with Tis, and loss of the normal allele was found in five of these cases. Eight of the 10 mutations occurred within highly conserved domains, but no mutational hot spots were found. GC to AT transitions were the most frequent mutations (six of 10 cases), while mutations at CpG dinucleotides were found in three cases (30%). AT to TA transversions were the second most frequent mutation (20%). The level of expression of p53 protein was assessed by Western blot analysis in 62 cases. Overexpression of p53 protein was detected in 21 of 62 cases (34%) including a case with Tis. There was a strong correlation between missense mutations in the p53 gene and overexpression of p53 protein. Overexpression of p53 protein was closely associated with increasing tumour size and ER-negative status among the various factors investigated, suggesting that p53 overexpression may reflect the lack of differentiation in breast cancer.

Immunohistochemical c-erbB-2 protein overexpression was detected in 34 of 124 (27.4%) paraffin-embedded breast cancer specimens. Although no difference was seen between the c-erbB-2 positive and negative groups in 5-year disease-free survival, 5-year overall survival was significantly less favorable in the c-erbB-2 positive group. Furthermore, patients graded as having positive c-erbB-2 staining and aneuploid DNA showed significantly poorer survival than those in other categories. The significant prognostic factors, determined by a multivariate analysis, were nodal status and c-erbB-2 overexpression. Our findings therefore suggest that c-erbB-2 expression is a prognostic factor in breast cancer and that it could be useful in the determination of postoperative adjuvant therapy.

The relationship of estrogen receptor(ER) status to DNA ploidy was investigated in 121 patients with breast cancer who underwent surgery. Lymph node status was evaluated histologically and ER levels were determined by the dextran-coated charcoal method, with a level of 3 fmol/mg·protein being considered positive. Flow cytometric DNA content was analyzed using paraffin-embedded tissue blocks. Sixty-three per cent of the specimens were ER+, while 37 per cent were negative. Sixty-one patients (50.4 per cent) were diploid and 60 aneuploid. A statistically significant correlation between the ER positivity rate and diploid DNA was found. Higher ER levels were seen in the postmenopausal patients with diploid tumors than in those with aneuploid tumors and there was a significant tendency for ER levels to be higher in the diploid tumors. Nodal status was not correlated with ER positivity or ploidy pattern. The present results indicate that ER levels are correlated with DNA ploidy, and reflect the degree of functional differentiation.

A case of breast cancer concurrent with hyperthyroidism was reported and the relation between breast cancer and thyroid dysfunction was reviewed. It has been frequently suggested that the incidence of breast cancer is decreased in patients with hyperthyroidism and breast cancer co-incidental with hyperthyroidism is rare.