Alternative use of multiple exons 1 of aromatase gene in cancerous and normal breast tissues from women over the age of 80 years.

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.

Histopathological assessment of anastrozole and tamoxifen as preoperative (neoadjuvant) treatment in postmenopausal Japanese women with hormone receptor-positive breast cancer in the PROACT trial.

PURPOSE: The PReOperative 'Arimidex' Compared with Tamoxifen (PROACT) trial compared neoadjuvant anastrozole and tamoxifen in postmenopausal women with large, operable or potentially operable, locally advanced hormone receptor-positive breast cancer. Here, we compare objective clinical responses with histopathological tumor responses to therapy in a cohort of 97 Japanese patients, in order to investigate the consistency of assessment methods and the change in estrogen-receptor (ER) and progesterone-receptor (PgR) status. METHODS: Histopathological response and the change in ER and PgR status were assessed by comparing pathological specimens collected at baseline (via needle biopsy) with those collected at 3 months (from excised tumors). The response was evaluated using Pathological Response Criteria for Breast Cancer as defined by the Japanese Breast Cancer Society. The patients were randomized to receive anastrozole (n = 48) or tamoxifen (n = 49). RESULTS: A numerically greater histopathological response rate was observed when neoadjuvant anastrozole compared with neoadjuvant tamoxifen (35.4 and 12.2%, respectively). The histopathological and clinical objective response rates agreed in 63/97 patients. The ER status of 5/40 patients changed from positive at baseline to negative at 3 months in the anastrozole group compared with 20/37 patients in the tamoxifen group. The PgR status of 16/17 patients in the anastrozole group and of 1/11 patients in the tamoxifen group changed from positive to negative. CONCLUSIONS: These data support the findings of the main PROACT trial, which confirmed that anastrozole, as compared with tamoxifen, is an effective neoadjuvant endocrine treatment in objective response rates for postmenopausal women with large operable hormone-receptor positive breast cancer. Further follow-up is required to confirm whether histopathological responses to therapy correlate with an overall improvement in survival.

Predictive implications of nucleoside metabolizing enzymes in premenopausal women with node-positive primary breast cancer who were randomly assigned to receive tamoxifen alone or tamoxifen plus tegafur-uracil as adjuvant therapy.

Recent studies have demonstrated that tegafur-uracil (UFT) is useful for the adjuvant treatment of various types of cancers. To determine whether nucleoside metabolizing enzymes could be used to predict the response to UFT treatment in women with primary breast cancer, we retrospectively analyzed archived tumor tissue samples obtained from the 3rd Adjuvant Chemo-Endocrine Therapy for Breast Cancer (ACETBC) study, in which adjuvant treatment with tamoxifen (TAM) plus UFT for 2 years was compared with TAM alone for 2 years. Samples of tumor tissue were obtained from 192 premenopausal women with node-positive invasive breast cancer. The tissue samples were examined immunohistochemically to study the expression of thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD), as well as the expression of Her2 and p53. In patients with TS-positive tumors, the risk of relapse was significantly lower in the tamoxifen plus UFT group than in the tamoxifen alone group. After 2 years, however, there was a trend towards a decrease in the relative predictive value (RPV) of TS with time. No relationship to outcome was detected for TP or DPD. Expression of Her2 or p53 was a significant prognostic indicator in the tamoxifen alone group. TS, but not TP or DPD, may be a useful predictor of response to UFT therapy. After 2 years, the RPV of TS decreased with time, suggesting that 2 years of treatment with oral fluorouracil derivatives may be inadequate. Further studies are required to investigate this possibility.

Diagnostic mammography and ultrasonography for palpable and nonpalpable breast cancer in women aged 30 to 39 years.

PURPOSE: To investigate the relationship between the tumor size of breast cancer by palpation and the sensitivity of mammography (MMG) and ultrasonography (US), and which modality can detect nonpalpable breast cancer in women aged 30 to 39 years. METHODS: We retrospectively evaluated the tumor size by palpation, breast density, and the sensitivity of MMG and US in 165 patients aged 30 to 39 years. Palpation, US, and MMG were performed with prior knowledge of the results of other modalities. The tumor size on palpation were classified into Tnp; nonpalpable, T1p; 2 cm or less, T2p; more than 2 cm, but not more than 5 cm, and T3p; more than 5 cm. RESULTS: Of 165 patients, 147 patients (89%) showed mammographically dense breasts. Of 165 cancers, 14 (8%) were Tnp, 40 (24%) were T1p, 82 (50%) were T2p, and 29 (18%) were T3p. The sensitivity of MMG was 57% (8 of 14) for Tnp, 78% (31 of 40) for T1p, 90% (74 of 82) for T2p, and 97% (28 of 29) for T3p. The sensitivity of US was 43% (6 of 14) for Tnp and 100% for palpable cancers. Of 14 nonpalpable cancers, 4 (29%), 4 (29%), and 2 (14%) could be detected by only MMG, bloody nipple discharge, and US. CONCLUSIONS: The sensitivity of MMG depends on the tumor size on palpation in this age range. MMG fails to detect relatively large palpable cancers. On the other hand, US can detect all palpable cancers. However, the sensitivity of US declines for nonpalpable cancers. For the detection of nonpalpable cancers, MMG, US, and nipple discharge are complementary modalities.

Malignant melanoma originating on the female nipple: a case report.

We report a very rare case of malignant melanoma arising on a female nipple. A 42-year-old housewife had suffered from a small dark brown nevus on her left nipple for about thirty years without any changes. Six months before her initial visit it had begun to enlarge and rapidly changed from dark brown to black. A small bleeding ulcer was also present in the center of the lesion. Malignant melanoma rather than mammary Paget's disease was suggested based on its clinical course. Excisional biopsy was performed to differentiate between mammary Paget's disease and malignant melanoma. The histopathological examination revealed malignant melanoma, about 4 mm in thickness. She then underwent wide excision with axillary lymph node dissection. The surgical margin was made in a 3 cm radius around the biopsy site. The excision included nipple, areola, and part of the underlying breast parenchyma, adipose tissue and corresponding superficial layer of fascia. Microscopy showed metastasis in one of 13 axillary lymph nodes. After the operation, the patient received adjuvant DAV-Ferron therapy. In such a case, conserving surgery based on correct diagnosis can achieve a good cosmetic result and optimal tumor control.

Diagnostic ultrasonography and mammography for invasive and noninvasive breast cancer in women aged 30 to 39 years.

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.

Estrogen-metabolizing enzymes in breast cancers from women over the age of 80 years.

CONTEXT: Aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase (EST) and HSD-2 down-regulate, the synthesis of active and more potent estrogens. These estrogen-metabolizing enzymes (EMEs) are important in postmenopausal breast cancers, but have never been systematically examined in breast cancers of the elderly. OBJECTIVE AND DESIGN: mRNA levels of EMEs in cancerous and normal breast tissues from 39 elderly patients (age, 80-99 yr) were compared with those from 39 controls (age, 37-70 yr) or compared according to estrogen (ER)/progesterone (PR) receptor status. RESULTS: Aromatase levels were higher in cancers of the elderly (EldCa) than in normal tissue of the elderly (P = 0.0008) or cancers of controls (P = 0.0033). In contrast, levels of steroid sulfatase and EST were higher in cancers of controls than normal tissue of controls (P = 0.0046 and P < 0.0001, respectively) or EldCa (P = 0.0001 and P < 0.0001, respectively). Levels of HSD-1 and HSD-2 did not differ significantly between any two of the categories. Among EldCa, HSD-1 levels were higher in ER/PR-positive than in ER/PR-negative carcinomas, whereas EST and HSD-2 exhibited opposite results. CONCLUSIONS: The importance of aromatase is relatively increased in EldCa. ER/PR-positive EldCa exhibited a pattern of EMEs more beneficial to the production of estrogen than did ER/PR-negative EldCa. The specific pattern exhibited in EldCa may elucidate the role of EMEs in the absence of ovarian estrogens in the pathogenesis of breast cancer.

Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid protein-15 as markers of apocrine carcinoma of the breast.

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.

Expression of E-cadherin, alpha-catenin, and beta-catenin in tubulolobular carcinoma of the breast.

Tubulolobular carcinoma (TLC) of the breast is a rare subtype of breast carcinoma categorized by Fisher et al. (Hum Pathol 8:679-683, 1977) as a tubular variant of lobular carcinoma. E-cadherin is a transmembrane glycoprotein, and complete loss of E-cadherin expression has been observed in invasive lobular carcinoma. Ductal carcinoma retains at least some expression of E-cadherin. Moreover, the adhesive function of E-cadherin is dependent on the integrity of the catenin components, which link E-cadherin to the actin filaments. In order to achieve improved categorization of TLC, we decided to investigate both E-cadherin and the catenins in TLCs and invasive lobular carcinomas. We reviewed all 1,430 cases of primary breast carcinoma that were surgically resected at Saitama Medical Center, Saitama Medical School, and at Saitama Red Cross Hospital between 1990 and 2005. Among these, 16 cases of TLC were reported retrospectively. The results were compared with those of 20 cases of invasive lobular carcinomas that were included as controls. Tumor tissue was immunostained for E-cadherin, alpha-catenin, and beta-catenin. The presence of immunoreactivity in the TLC was seen in 12 (75%) cases for E-cadherin, in 8 (50%) cases for alpha-catenin, and in 10 (62.5%) cases for beta-catenin. However, plasma-membrane-associated staining for E-cadherin, alpha-catenin, and beta-catenin was completely absent in invasive lobular carcinomas. These results suggest the possibility that TLCs are not a variant of lobular carcinoma, but rather ductal carcinomas with a lobular growth pattern.

Intraductal papilloma with bloody discharge from Montgomery's areolar tubercle examined by ductoscopy from the areola.

A patient with intraductal papilloma who had abnormal bloody discharge from Montgomery's areolar tubercle underwent mammary ductography, mammary ductoscopy from the tubercle, and microdochectomy.A 43-year-old woman who was being followed-up for left breast cancer noticed bloody discharge from Montgomery's areolar tubercle of the right breast. Because the discharge continued for 2 months, further examinations were conducted. Mammary ductoscopy of Montgomery's areolar tubercle showed a normal internal duct structure. The presence of yellowish superficial lesions suggested intraductal inflammation or superficial hyperplasia of the duct epithelium. Lavage cytology revealed benign papillary lesions. Since the discharge continued and we could not completely exclude malignancy, microdochectomy was performed. Histologically a lactiferous duct was connected to Montgomery's areolar tubercle and an intraductal papilloma was seen in part and considered to have caused the bloody discharge. Bloody discharge from Montgomery's areola tubercles is extremely rare, the present case was our first experience with ductoscopy of Montgomery's areolar tubercle out of 641 cases of mammary ductoscopy performed on patients with bloody nipple discharge from 1998 to 2004. In our case, Montgomery's areolar tubercles were connected to a lactiferous duct. Although there are a few breast carcinomas that cause bloody discharge and eruption of areola, areolar preservation should be performed with the knowledge that disease may also involve the areola through the lactiferous ducts.

High prevalence of HER-2/neu and p53 overexpression in inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. Although the survival of patients with IBC has been greatly improved by the use of combined treatment modalities, women with IBC still have lower survival rates. We have summarized a single-center experience involving IBC patients. Our objectives are to clarify molecular alterations of HER-2/neu and p53 in IBC and to investigate the prognostic factors. METHODS: Between January 1990 and December 2000, 57 patients with IBC were referred to the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The incidence of IBC among primary breast cancers was 1.0% (57/5,757) in our hospital. Forty-six patients meeting Haagensen's criteria for inflammatory breast carcinoma were evaluated. All patients had biopsy-proven carcinomas but no distant metastases at referral. The median age at diagnosis for IBC was 51.8 (range, 28 to 70). All patients underwent a mastectomy. Chemotherapy was performed pre- or post-operatively. Three-year and 5-year survival rates were 56.5%, and 40.7%, respectively. Expressions of HER-2/neu and the p53 protein were determined retrospectively by immunohistochemical (IHC) staining of thin paraffin-embedded sections of primary tumors. RESULTS: Of 46 patients, 23 (50.0%) with tumors testing positive for HER-2/neu fared somewhat worse than those with negative tumors, but the differences were not significant for either overall survival (OS) or disease-free survival (DFS). Of 46 patients, 19 (41.3%) whose tumors were positive for p53 fared somewhat better than patients with negative tumors, with no significant differences in either OS or DFS. Patients presenting with less than ten pathologically involved axillary lymph nodes showed significantly better OS and DFS. CONCLUSIONS: Overexpression of HER-2/neu and the p53 protein were not significant prognostic factors in inflammatory breast cancer. However, the increased incidence of HER-2/neu and the poor outcome of IBC may be of clinical interest, suggesting the need for clinical trials of antibody therapy targeted to HER-2/neu. Moreover, a high prevalence of p53 may be useful in determining the specific use of chemotherapy.

Efficacy and safety of combined trastuzumab and Paclitaxel therapy as a second-line treatment in women with metastatic breast cancer: a single institutional experience.

BACKGROUND: In breast cancer, HER-2 overexpression suggests s poor prognosis. Trastuzumab is a humanized monoclonal antibody with specificity to the HER-2 protein. We evaluated the safety and efficacy of combined trastuzumab and paclitaxel therapy in women with metastatic breast cancer. PATIENTS AND METHODS: Combination chemotherapy was given to patients with HER-2 overexpressing metastatic breast cancer. All patients had previously received one or more chemotherapy treatments. Patients received a loading trastuzumab dose of 4 mg/kg intravenously (i.v.), followed by 2 mg/kg maintenance dose at weekly intervals. A paclitaxel dose of 80 mg/m(2) was administered on the same day as the trastuzumab infusion. RESULTS: A total of 53 patients were examined. Seventy percent received two or more prior chemotherapy treatments for metastatic breast cancer, and 66.0% of patients had two or more metastatic sites. The overall response rate to our approach was 37.7%. Median time to progression was 12.0 months. Grade 3/4 neutropenia was seen in only 11.3% of patients. Peripheral neuropathy occurred in 65.1% of patients after seven treatments, requiring us to change to biweekly paclitaxel administration in 16 patients. Most of them were able to continue the treatment. Other toxicities were mild and tolerable. CONCLUSION: Combined trastuzumab and paclitaxel therapy, administered as second-line or later treatment, produced lasting objective responses and was well tolerated by women with HER-2 overexpressing metastatic breast cancer. A major obstacle to continuing treatment was peripheral neuropathy. However, modifying the interval to every 2 weeks enabled us to continue the treatment. This combination chemotherapy was safely performed in our outpatient clinic.

[The role and efficacy of Mammotome biopsy (vacuum-assisted breast biopsy)].

Mammotome (Vacuum-assisted Breast Biopsy System) is a device for needle biopsy of the breast which is useful for the biopsy of non-palpable lesions. Although Mammotome biopsy is performed on mammography or ultrasound guided, mammography -guided (stereotactic) Mammotome is more important because it is almost only devise for the biopsy of non-palpable microcalcifications. We performed 1000 cases of stereotactic Mammotome biopsy between February 2000 and February 2005 in Cancer Institute Hospital, 31% of the cases were diagnosed as cancer, among these cases 83% were noninvasive carcinoma and 17% were invasive. Of the cases which Mammotome revealed noninvasive carcinoma 17% were found to have invasive lesions after the operation. Mammotome is useful device for the diagnosis of early breast cancer.

Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast.

Medullary carcinoma (MC) of the breast is characterized by large anaplastic cells and infiltration by benign lymphocytes. Patients with this pattern of breast carcinoma are considered to have a better prognosis than those with other histological subtypes. We reviewed cases of primary breast carcinoma that were surgically resected between 1990 and 2004. Of these, 13 cases of medullary carcinoma of the breast with lymphocyte infiltration were reported. Tests for CD3, CD4, CD8, CD20, CD56, TIA-1, and granzyme B were performed on paraffin sections. We found that the MC contained very few NK cells, as assessed by their reactivity with the CD56 antibodies. However, MC had a significantly greater percentage of CD3, CD8, TIA-1, and granzyme B lymphocytes infiltrating the stroma of the tumor. Furthermore, more CD8-positive than CD4-positive T-cell lymphocytes were present within the tumor cell nests in MC, as opposed to the proportion in usual ductal carcinoma. The infiltrating cytotoxic/suppressor T cells in MC represent host resistance against cancer, and the high grading of the T-cell infiltration could explain, in part, a key mechanism controlling the good prognosis for this type of tumor and solve the pathological paradox of MC.

Clinical and pathological features of glycogen-rich clear cell carcinoma of the breast.

BACKGROUND: Twenty cases of invasive ductal carcinoma of the breast with a pure or partial glycogen-rich clear cell carcinoma(GRCC)component are reported. GRCC of the breast is composed almost entirely of polygonal cells with clear cytoplasm. These contain large amounts of partly water-soluble glycogen. METHODS: The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, axillary lymph node and Her2/neu status. RESULTS: Between 1990 and 2004, 723 patients with primary breast carcinomas were treated and clinicopathologic analysis was performed. 20 cases were identified as GRCC among the 723 cases. The patients' age at presentation ranged from 33 to 68 years (mean, 52 years). Tumor size ranged from 1 to 6.5 cm (mean, 2.6 cm); 35% (7 of 20) of cases that underwent axillary dissection had positive lymph nodes. Among 15 of 20 cases who were followed for 1-72 months, 5 cases died from their breast carcinoma within 5 years following the diagnosis. CONCLUSION: Our series included more small size carcinomas than did previous series. Lymph node status does not appear to be markedly different from that of the usual invasive ductal carcinomas. Her2/neu expression was similar to that found in common breast carcinomas.

Spontaneous " healing" of breast cancer.

BACKGROUND: Healing is a phenomenon by which the intraductal component of breast cancer disappears and is replaced by fibrous tissue. Focally localized healing often prevents confirmation of the continuity of intraductal carcinoma. OBJECTIVE: To clarify the clinicopathological characteristics of breast cancer with healing. PATIENTS AND METHODS: At our hospital, 308 patients (311 breasts) underwent breast conservation therapy without neoadjuvant chemotherapy for breast cancer in 2000. These surgical specimens were histopathologically investigated with 5 mm serial sections. We assessed the proportion and the characteristics of breast cancer with healing. RESULTS: (1) The proportion of breast cancer with healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and the mean diameter was 2.8 cm. (3) The histological type of the breast cancer varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5, solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular carcinoma in 1, and Paget's disease in 1. However in all cases, the histologic type of the intraductal carcinoma foci was the comedo/solid type and the nuclear grade of cancer cells was high. (4) In cases with healing, areas of healing were seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in 8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was seen at the surgical margin of the partial mastectomy specimen. CONCLUSION: The proportion of breast cancer cases with healing was 7% and these cases were intraductal carcinoma of the comedo/solid type, consisting of highly malignant cancer cells.

Postoperative prognosis of node-negative breast cancers predicted by gene-expression profiling on a cDNA microarray of 25,344 genes.

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.

Classification of ipsilateral breast tumor recurrence after breast-conserving therapy: new primary cancer allows a good prognosis.

PURPOSE: To classify and assess ipsilateral breast tumor recurrences (IBTR) after breast-conserving therapy. METHODS: Between 1986 and 2001, 2,137 patients who had breast cancer underwent breast-conserving surgery with or without radiotherapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. Of these patients, 83 (3.9%) had an IBTR. We classified the IBTR as a new primary cancer (NP) if the primary tumor had completely negative margins at first operation by detailed pathological examination and if the IBTR had an intraductal component. All other IBTRs were judged true local recurrence (TR). RESULTS: Of the 83 patients, 42 patients were classified as TR (29 had no radiotherapy) and 41 as NP (40 had no radiotherapy). Mean time to disease recurrence was 37 months for TR (52% were within 2 years) versus 55 months for NP (19% were within 2 years) (p=0.031). Six patients (14%) with TR did not receive re-operation, and 67% received salvage mastectomy and 19% re-lumpectomy. All cases of NP were operable, 78% underwent salvage mastectomy and 22% underwent re-lumpectomy. Distant metastases were observed in 33% of patients with TR and 5% of patients with NP, and cause-specific death occurred in 6 cases with TR and in one with NP. The patients with NP had improved 5-year rates of overall survival (NP 91% vs. TR 76%, P=0.0627) and distant disease-free survival (NP 93% vs. TR 61%, P=0.0028). Patients with NP more often developed contralateral breast cancer (NP 37% vs. TR 12%, P=0.018) CONCLUSIONS: Patients with NP had better survival rates than those with TR. Distinguishing new primary breast carcinomas from local disease recurrences may have importance in therapeutic decisions and chemoprevention strategies.

A case of carcinosarcoma of the breast.

Carcinosarcoma is a rare malignant tumor of the breast. A 59-year-old woman was admitted to our hospital with a complaint of a right breast mass for one month. The mass grew rapidly, and modified radical mastectomy was performed. Based on the histological findings of carcinomatous and sarcomatous components entangled without a transition area, and the results of immunohistochemical staining, carcinosarcoma of the breast was diagnosed. Within 9 months of the surgery, a recurrent lesion appeared in her chest wall. As shown by local resection, this recurrent tumor had only a carcinomatous component. Such tumors are very rare, and there have been no detailed reports of recurrence patterns of carcinosarcoma. Here we report our pathological findings in detail.

Huge cavernous hemangioma arising in a male breast.

We report a rare case of a huge cavernous hemangioma arising in a male breast. A 60-year-old man first noticed 1 x 2 cm elastic hard nodule just below his right nipple ten years previously. It enlarged 5 x 5 cm over six years. When he came to our clinic, it was size of child head (510 mm in circumference),was an elastic hard with a rather smooth surface, and firmly fixed to the chest wall. Magnetic resonance imaging (MRI) and multidetectocomputed tomography (MDCT)showed a large mass infiltrating into the chest wall. Fine needle aspiration cytology (FNA) and core needle biopsy (CNB) failed to obtain proper material except for old bloody fluid or necrotic connective tissue, precluding a correct diagnosis preoperatively. Mastectomy with partial resection of the chest wall was subsequently performed. Histologically, it was found to be a cavernous hemangioma without cellular atypia. In such a case, complete excision is recommended to exclude the possibility of an underlying malignant lesion.