PURPOSE: To evaluate the prognostic significances of angiogenesis and bc1-2, and association of each other, we investigated the correlation of microvessel count for angiogenesis and bcl-2 expression in breast cancer. MATERIALS AND METHODS: We analysed immunohistochemistry staining from paraffin blocks in a series of 145 women with breast cancer. Immunohistochemical staining to detect factor VIII-related antigen highlighted the microvessels within primary invasive breast carcinoma. Using light microscopy, we counted microvessels per 200X field in the most active areas of neovascularization. To determine the bcl-2 immunoreactivity, we used a monoclonal antibody directed against the bcl-2 protein. RESULTS: The median of microvessel count (MVC) was 31.5, and the proportions of tumors with low and high MVC were 51% and 49%. Eighty (55.2%) cancers showed the bcl-2 immunoreactivity in the cytoplasm. The microvessel count were correlated with lymph node status (p <0.001), tumor size (p=0.001), and lymphatic invasion around tumor (p=0.009). bcl-2 expressions were corelated with estrogen receptor positivity (p<0.001) and progesterone recepter positivity (p=0.029). The microvessel counts were negatively correlated with bcl-2 expression (p=0.006). CONCLUSION: This study suggest that the angiogenesis which was investigated by micro- vessel counts was negatively correlated with bcl-2 expression.
Breast Neoplasms* ; Breast* ; Cytoplasm ; Estrogens ; Female ; Humans ; Immunohistochemistry ; Lymph Nodes ; Microscopy ; Microvessels ; Paraffin ; Progesterone ; von Willebrand Factor

PURPOSE: c-erbB2 encodes 185 kDa oncoprotein with tyrosine kinase activity and has homology to the epidermal growth factor receptor. c-erbB2 proto-oncogene is found to be overexpressed in approximately 20 to 30% of primary breast cancer and has been associated with poor prognosis and lower response to conventional chemotherapy. MATERIALS AND METHODS: We perfonned a study on 40 infiltrating ductal breast cancers treated with primary surgery and adjuvant chemotherapy. We investigated c-erbB2 expression by immunohistochemistry in paraffin-embedded tissue using polyclonal antipeptide antibody(DAKO). We evaluated the relationships between its expression and the results after over 6 cycles of adjuvant chemotherapy including cyclophosphamide, methotrexate and 5-FU. RESULTS: The median age at diagnosis was 43 years and the median follow-up time was 47.3 months. Thirteen(32.1%) of 40 patients showed the c-erbB2 overexpression in the external domains of protein. There were no correlations among c-erbB2 amplification and other prognostic factors such as hormonal receptors, histologic grade and tumor size. Estrogen receptor and progesterone receptor showed tendency of inverse correlation with c-erbB2 overexpression but it was not statistically significant(p>0.05). c-erbB2 positive patients showed shorter disease free survival compared to c-erbB2 negative patients in univariate analysis(p<0.05)(Kaplan Meire analysis). The patients without c-erbB2 overexpression seemed to survive longer but had no significant survival benefit(p>0.05). CONCLUSION: These findings suggest that overexpression of c-erbB2 may be a marker of poor response to adjuvant chemotherapy with CMF regimen and may be an indicator of more aggressive therapy.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Cyclophosphamide ; Diagnosis ; Disease-Free Survival ; Drug Therapy* ; Estrogens ; Fluorouracil ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Methotrexate ; Prognosis ; Protein-Tyrosine Kinases ; Proto-Oncogenes ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone

PURPOSE: We tried to find the patients characteristics of parasternal recunence, to classify the parasternal recunence according to the radiological and clinical features, and to evaluate the efficacy of local radiotherapy. MATERIALS AND METHODS: Between August 1987 and April 1997, twenty one patients with parastemal recurrence of breast cancer after surgery with or without adjuvant chemotherapy were treated with radiotherapy. Age distribution at initial operation was ranged from 31 to 79 years(median 48 years). Sixteen(76.2%) cancers were in the right breast and five(23.8%) were in the left. The pathologic types were infiltrative ductal carcinoma in 18 patients and medullary carcinoma in 3 patients. Eight patients had stage I, three had stage IIa, six had stage IIb, one had stage IIIa diseases and we had no information about the initial stage of the other 3 patients. Parasternal recurrence were diagnosed by biopsy in 7 patients, and the other 14 recurrences were diagnosed by clinical and radiologic findings such as chest CT, whole body bone scan. All the patients were treated with radiation for the parasternal recurrent tumors. In addition, five patients also received chemotherapy(FAC or Taxol based protocol) and one patient also received partial resection before radiotherapy. Radiotherapy was delivered with Co-60 gamma-ray or 4~6 MV X-ray or electron beam to both supraclavicular lymph nodes and parasternal areas with total doses of 3000~6480 cGy(median 6100 cGy). RESULTS: The range of interval between curative resection and parasternal recurrence were 4~110 months(median 34 months). The main symptoms of the parasternal recurrence were a painless mass(n=10). The duration of symptom before diagnosis ranged from one to 36 months(median 7 months). Among 21, five patients(23.8%) presented distant metastses at the diagnosis of parasternal recurrences. The parasternal recurrences were classified into three groups according to radiologic and clinical findings; the recurrent tumors originated from sternum and invaded into adjacent tissues(Group 1, n=5), tumors originated from intemal mammary lymph nodes and invaded into sternum or parasternal tissues(Group 2, n=6), tumors originated from medial chest wall and invaded into sternum or parasternal tissues(Group 3, n=10). In nineteen patients(19/21; 90.5%) there was complete response of parasternal recurrence following radiotherapy. Although the follow up period was relatively short(3~78 montbs, median 14 months), there were no local recurrence in radiation field in 19 patients with complete response. Among the 16 patients without distant metastases at diagnosis of parasternal recurrence, nine patients were alive without any evidence of disease. CONCLUSION: Chest CT scan is necessary and effective in patients with parastemal discomfort, pain, swelling or palpable mass after mastectomy. And we found that radiotherapy was very effective for the local treatment of parasternal recunence in terms of symptom palliation and local control of tumor. Although we classified the parasternal recurrence into three groups, we could not reach any conclusive results because of short follow up duration and insufficient patients number.
Age Distribution ; Biopsy ; Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Carcinoma, Medullary ; Chemotherapy, Adjuvant ; Diagnosis ; Follow-Up Studies ; Humans ; Lymph Nodes ; Mastectomy ; Neoplasm Metastasis ; Paclitaxel ; Radiotherapy ; Recurrence* ; Sternum ; Thoracic Wall ; Tomography, X-Ray Computed

PURPOSE: The natural history of patients with ductal carcinoma in situ (DCIS) with microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used arbitrary criteria for the evaluation of microinvasion. METHODS: In order to compare the clinicopathologic features and treatment outcomes between DCIS and DCIS with microinvasion, the medical records of 101 patients of DCIS with or without microinvasion who had been treated at Yongdong Severance hospital from April 1991, to October 1998, were reviewed retrospectively. RESULTS: The mean age of the DCIS with microinvasion group was 44.8 years-old and that of the DCIS group was 47.4 years-old. The peak age group within both study groups was the 5th decade. The primary tumors of the DCIS-MI group were larger (2.16 vs 1.93 cm) and more easily palpated (66.3% vs 36.6%) upon the physical examination than that of the DCIS group. The rate of axillary lymph node metastasis was higher in the DCIS-MI group (10% vs 1.3%). In terms of nuclear grade, comedo type, hormone receptor status, and c-erbB2 immunohistochemical positivity, there were no statistically significant differences between the DCIS and DCIS-MI groups. The recurrence rate within the DCIS-MI group was higher than that of DCIS group (10% vs 1.4%). The 5-year disease free survival rate of the DCIS and DCIS-MI groups were 98% and 89% respectively. CONCLUSION: Ductal carcinoma in situ with microinvasion is thought to be a transitional disease entity between ductal carcinoma in situ and invasive ductal carcinoma. However, the treatment options for ductal carcinoma in situ with microinvasion have been similar to that of the invasive carcinoma. More long-term follow-up and a multicenter study seem to be necessary to identify differences in the clinical features and to determine the optimal methods of treatment.
Axilla ; Breast Neoplasms ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Disease-Free Survival ; Humans ; Lymph Nodes ; Medical Records ; Natural History ; Neoplasm Metastasis ; Physical Examination ; Recurrence ; Retrospective Studies

PURPOSE: The axillary lymph node status is the most important prognostic factor in breast cancer. The axillary node dissection is usually performed in infiltrating brcast cancer for the information of therapeutic decision and prediction of prognosis. But this procedure may result in lymphedema of affected upper extremity nearly about 25%, increased axillary drainage, sensory abnormality and pain. Many researches are focussed to find the patients group who do not need axillary dissection according to the status of tumor size, patient age, hormonal receptor and histologic grade. MATERIAL AND METHODS: We evaluated the axillary lymph node status in patients with tumor size less than 2 cm in diameter and thein correlation of other prognostic factor. We reviewed 127 women with histologically diagnosed infiltrating ductal carcinoma of breast who were treated by one surgeon at Yongdong Severance Hospital, Yonsei University College of medlcine between 1991 and 1996. RESULTS: Five patients (3.9%) had Tla lesion (<5 mm), 24 patients (18.9%) had Tlb tumors (6-10 mm), and 98 cases (77.2%) had Tlc lesion (11-20 mm). The average numbers of axillary lymph nodes dissected were 14.2. We found that smallcr tumor size, good histologic grade, estrogen receptor positivity, old age (over 50 years) showed a tendency of decreased axillary node metastasis but without statistical significance. CONCLUSION: There are possibility of finding subset with low risk of axillary lymph node metastasis in small sized tumor with addition of good prognostic indicators such as good histologic grade, hormonal receptors and old age.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Drainage ; Estrogens ; Female ; Humans ; Lymph Nodes* ; Lymphedema ; Neoplasm Metastasis* ; Prognosis ; Upper Extremity

Cyclin/cdc complexes are known to function in cell-cycle regulation. Cyclin D1/cdk4 and -6 complexes, which functions as a G1-S checkpoint and cyclin B1/cdc2 complexes, a G2-M checkpoint are essential for DNA synthesis and mitosis, respectively. Thus, dysregulated overexpression of cyclins appears to be involved in uncontrollable cell proliferation and early tumor development. We investigated the expression and proliferative index of cyclin D1 (PIcyclin D1), cyclin B1 (PIcyclin B1) and Ki-67 (PIKi-67) using immunohistochemical staining on 15 cases of ductal hyperplasia (DH), 26 cases of atypical ductal hyperplasia (ADH) and 43 cases of ductal carcinoma in situ (DCIS) of the breast in order to evaluate whether these cyclins are associated with abnormal cell proliferation and play a role in tumor development from ADH to carcinoma. Furthermore, we investigated whether the expression and proliferative index of the cyclins and Ki-67 are correlated with the histologic grade according to the Van Nuys classification and with the histologic subtype according to traditional classification. Finally, we estimated the correlation coefficient among PIcyclin D1, PIcyclin B1, PIKi-67 and estrogen receptor in ADH and DCIS. The expression of cyclin D1 was detected in 39.5% of DCIS and 7.7% of ADH cases. In the DH cases, expression of cyclin D1 was not found. Expression of cyclin B1 was also detected in 69.7% of DCIS, 50.0% of ADH and 93.3% of the DH cases. The PIcyclin D1 was significantly different among these three groups. Moreover, the PIcyclin D1 and PIKi-67 were differed significantly between the low grade DCIS and ADH cases. However, PIcyclin B1 only appeared to be significantly different between the total DCIS and ADH. Results of the correlation coefficient among PIcyclin D1, PIcyclin B1 and PIKi-67 were positively correlated with each other. No significant correlation was found between the expression of ER and cyclin D1 in ADH and DCIS. In summary, our results support the hypothesis that a cyclin D1 and cyclin B1 protein aberration, along with Ki-67, may act as a relatively early event in the tumor development from ADH to carcinoma.
Breast/pathology* ; Breast/metabolism* ; Breast Neoplasms/pathology* ; Breast Neoplasms/metabolism* ; Carcinoma, Infiltrating Duct/pathology* ; Carcinoma, Infiltrating Duct/metabolism* ; Cyclins/metabolism* ; Female ; Human ; Hyperplasia ; Ki-67 Antigen/metabolism

The initial presentation of breast malignancy as noninvasive carcinoma in an area of sclerosing adenosis is unusual. Especially, lobular carcinoma in situ in sclerosing adenosis sometimes can be a potential source of confusion with invasive lobular carcinoma. We report a case of lobular carcinoma in situ presenting in adenosis exhibiting patterns akin to invasive lobular carcinoma, thus leading to potential misdiagnosis. Overall architecture of the lesion as seen at lower power and immunohistochemistry can be useful to distinguish between sclerosing adenosis with lobular carcinoma in situ and infiltrating lobular carcinoma.
Breast Neoplasms/pathology* ; Carcinoma in Situ/pathology* ; Carcinoma, Lobular/pathology* ; Case Report ; Female ; Fibrocystic Disease of Breast/pathology* ; Human ; Immunohistochemistry ; Middle Age

PURPOSE: Oncogene c-erbB2 produces a transmembrane protein similar in structure to the tyrosine kinase family. Overexpression of c-erbB2 is known to lower the survival rate of breast cancer patients. c-erbB2 protein is an important antigen for tumor specific cytotoxic T lymphocytes induction that is dependent on its presentation as stably complexed with HLA-A2. In 1997, Nistico P reported low frequency of c-erbB2 proto-oncogene overexpression in HLA A2 positive breast cancer patients. And then in this study, correlation of HLA-A2 and the c-erbB2 expression was investigated in breast cancer patients. MATERIALS AND METHODS: HLA-A DNA typing by locus-specific generic PCR and by hybridization with sequence-specific oligonucleotide probes (SSOP) was performed on peripheral blood lymphocytes from 52 breast cancer patients (a PCR-SSOP typing method, involving a PCR amplification in conjunction with digoxigenin labelled sequence-specific oligonucleotide probes). To determine c-erbB2 expression, immunohistochemistry from paraffin-embedded tissues in a series of 47 patients with available tissue blocks was performed by use of rabbit anti-human c-erbB2 oncoprotein (DAKO, Glostrup, Denmark). And then we statistically analyzed the relation between the expressions of HLA-A2 and c-erbB2 in breast cancer patients. RESULTS: 29 out of 52 patients (55.8%) were HLA-A2 positive. 23.4% (11out of 47 patients) of breast cancer patients overexpressed c-erbB2. The patients with c-erbB2 overexpression showed lower estrogen receptor positivity compared to those without c-erbB2 overexpression (10.5%, vs 33.3%). HLA-A2 positive patients showed 18.5% (5/27) of overexpression and HLA-A2 negative patients showed 30.0% (6/20) of c-erbB2 overexpression (p=0.283). CONCLUSIONS: We observed no correlation between HLA-A2 and prognostic factors in breast cancer such as tumor size, axillary nodal status. However, our results showed a tendency without statistical significance between HLA-A2 and high frequency of c-erbB2 overexpression. More accumulation of patients will be needed for better conclusions.
Breast Neoplasms* ; Breast* ; Digoxigenin ; DNA Fingerprinting ; Estrogens ; HLA-A Antigens ; HLA-A2 Antigen* ; Humans ; Immunohistochemistry ; Lymphocytes ; Oligonucleotide Probes ; Oncogenes ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases ; Proto-Oncogenes ; Statistics as Topic ; Survival Rate ; T-Lymphocytes, Cytotoxic

BACKGROUND: The natural history of the patients of ductal carcinoma in situ(DCIS) with microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used and/or arbitrary criteria for the evaluation of microinvasion. METHODS: To compare the clinicopathologic features and the outcomes of treatment between DCIS and DCIS with microinvasion, the medical records of 101 patients of DCIS with/without microinvasion who had been treated at Yongdong Severance hospital from Apr. 1991, to Oct 1998, were reviewed retrospectively. RESULTS: The mean age of the patients of DCIS with microinvasion group was 44.8 years and that of the patients of DCIS group was 47.4 years. The peak age group of both was 5th decade. The primary tumors of DCIS-MI group were larger(2.16 vs 1.93cm) and more easily palpated(66.3% vs 36.6%) on the physical examination than that of DCIS group. The rate of the axillary lymph node metastasis was higher in DCIS-MI group.(10% vs 1.3%) In terms of nuclear grade, comedo type, hormone receptor status, and c-erbB2 immunohistochemical positivity, there were no statistical significances between DCIS group and DCIS-MI group. The recurrence rate of DCIS-MI group was higher than that of DCIS group.(10% vs 1.4%) The 5-year disease free survival rate of the DCIS group and DCIS-MI group were 98% and 89% respectively. CONCLUSIONS: Ductal carcinoma in situ with microinvasion is thought to be transitional disease entity between ductal carcinoma in situ and invasive ductal carcinoma. But the treatment options of ductal carcinoma in situ with microinvasion were similar to that of the invasive carcinoma. More long-term follow-up and multicenter studies seem to be necessary to identify differences in clinical features and to determine the optimal methods of treatment.
Axilla ; Breast Neoplasms ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Lymph Nodes ; Medical Records ; Natural History ; Neoplasm Metastasis ; Physical Examination ; Recurrence ; Retrospective Studies

BACKGROUND: In Korea, the incidence of breast cancer is relatively lower than in western country, but it is in increasing slope. However the mammographic patterns of Korean breast cancer patients are not well known. METHODS: The authors collected the clinical and radiologic data from new breast cancer patients between January 1992 and December 1997, and analysed the mammographic pattern. RESULTS: Of the 418 patients, the age-specific incidences were 153 (37.0%) for 40 to 49 years of age, 99 (23.9%) for 30 to 39 years, 81 (19.6%) for 50 to 59 years, 55 (13.3%) for 60 to 69 years, 14 (3.3%) for over 70 years, and 12 (2.9%) for 20 to 29 years. According to the TNM staging system, there were 2 (0.6%) with stage 0, 102 (24.9%) with stage I, 147 (35.9%) with stage IIA, 72 (17.6%) with stage IIB, 85 (20.8%) with stage IIIA, 1 (0.2%) with stage IV. The non-palpable lesions were 7.5% on physical examination. According to Wolfe's classification, there were 78 (19.0%) for N1, 78 (19.0%) for P1, 133 (32.4%) for P2, and 122 (29.7%) for DY pattern. On mammography, lumps were found in 312 cases (75.8%). Among mammographic lumps, 51.9% was not clearly defined margin. The mammographic calcifications were found in 48.3% of all patients. In the distribution of calcification, 20.6% was diffuse type and 79.4% was localized type. The size of calcifications was variable in 92.9% and the shape of calcifications was amorphous pattern in 85.6%. We could not suspect cancer in 14.7% of patients on mammography, and 10.1% of patients on ultrasound examination. CONCLUSION: We believe that these baseline mammographic data of Korean breast cancer patients may contribute to the accurate diagnosis of breast cancer, but more data will be needed.
Breast Neoplasms* ; Breast* ; Classification ; Diagnosis ; Humans ; Incidence ; Korea ; Mammography ; Neoplasm Staging ; Physical Examination ; Ultrasonography