Clinical Experience for Sentinel Lymphadenectomy Alone in Early Breast Cancer / 한국유방암학회지

PURPOSE: This study was performed to evaluate the efficacy and safety of sentinel lymph node biopsy alone (SLNB) without axillary lymph node dissection. METHODS: Between Jun. 1999 and Dec. 2002, we carried out SLNB in 85 consecutive patients with T1 breast cancer whose sentinel lymph node(s) were tumor-free on intra- operative frozen section. Even when sentinel lymph node(s) turned out to be positive by permanent pathology, additional axillary lymph node dissection was not performed. Patients underwent total mastectomy or partial mastectomy and received an appropriate adjuvant therapy according to the characteristics of the primary tumor. All patients who had breast conserving surgery received postoperative radiotherapy to the remaining breast, but not to the axilla. RESULTS: SLNB only took 14 minutes and yielded no postoperative complications. Among the 85 patients whose sentinel lymph nodes were tumor-free on frozen section, 11 patients were diagnosed as metastatic in the permanent pathology. One of them had a macro-metastasized (2.5 cm) sentinel lymph node, and the rest had micro-metastasized sentinel lymph nodes. For 23.1 months of mean follow-up period, all the patients including a patient who died of liver metastases at 17 months showed no evidence of axillary recurrence. CONCLUSION: No axillary recurrence following SLNB suggests that SLNB may be a good alternative to routine axillary lymph node dissection while providing less surgical morbidity in women with a small breast cancer. However, more patients accumulation and follow-up period will be needed for the final conclusion.

Sentinel Lymph Node Biopsy Using Radioactive Material in Breast Cancer Patients

PURPOSE: In breast cancer, the single most important prognostic indicator is the axillary nodal status of the metastasis. This study was designed to discern the accuracy of sentinel node biopsy using radioactive material for the prediction of axillary nodal status. METHODS: The study group was selected from the Department of Surgery at Yonsei University Yongdong Severance hospital, and comprised 54 patients diagnosed with breast cancer with clinical stages I or II from Nov. 1998 to May. 1999. We performed lymphoscintigraphy and gamma-probe with 99mTc-antimony trisulfide colloid for the detection of sentinel nodes. The radiotracer was injected peritumorily 2 hours prior to the operation. During, surgery and after the sentinel node biopsy was performed, level I and II axillary lymph node dissection was completed. The sentinel node was divided into 3 pieces evenly. One piece was tested for frozen section diagnoses and the others were fixed for H&E staining and immunohistochemistry (IHC) using cytokeratin antibody to detect metastasis. RESULTS: The mean number of the sentinel nodes was 1.59. The detection rate of the sentinel node was 94.4% (51/54). Among 35 patients with negative sentinel nodes on frozen section, 4 patients (11.4%) demonstrated tumor metastasis on both permanent serial H&E sections and IHC using cytokeratin. Of the 31 patients with negative sentinel node by permanent serial section, 4 patients displayed metastasis in nonsentinel axillary nodes. These results revealed that thesensitivity of the sentinel node biopsy was 83.3% and the negative predictive value was 81.1%. The false negative rate of the sentinel node biopsy was 16.7% with the permanent H&E and IHC section and 33.3% with the frozen section. In particular, in cases with tumors less than 2 cm, the sensitivity was 100% in frozen section as well as permanent section. CONCLUSION: A combination of preoperative lymphoscintigraphy and gamma probe-guided methods achieves high success rates in the identification of sentinel nodes. Multiple serial sections and IHC of the nodes are required to detect the micrometastasis of the sentinel nodes. The sentinel node biopsy is significantly accurate and may be considered as an alternative to replace the routine axillary node dissection, particularly in T1 breast cancer patients.

Clinicopathological Analysis of Ductal Carcinoma in situ (DCIS) and Ductal Carcinoma in situ with Microinvasion

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.

Expression of cyclins in ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ of the breast

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.

Lobular carcinoma in situ in sclerosing adenosis

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.

Sentinel lymph node biopsy using radioactive material in breast cancer patients / 한국유방암학회지

BACKGROUND: In breast cancer, the single most important prognostic indicator is the axillary nodal status of the metastasis. The sentinel lymph nodes are the lymph nodes of the primary tumor that is drained first, which can predict the presence of the tumor metastasis with high accuracy. This study was designed to find out how accurately the sentinel node biopsy using radioactive material can predict axillary nodal status. METHODS: The patients were selected from the department of surgery at Yonsei University Yongdong Severance hospital, consisting of 54 patients with breast cancer diagnosed as clinical stages I or II from Nov. 1998 to May, 1999. We performed lymphoscintigraphy and gamma-probe method with 99mTc-antimony trisulfide colloid for detection of sentinel nodes. The radiotracer was injected around the tumor 2 hours prior to the operation. In the operating room, after the sentinel node biopsy had been performed, levels II and II axillary lymph node dissection were completed. The sentinel node was divided into 3 pieces evenly. One piece was tested for frozen section diagnoses and the others were fixed in 10% formalin for H&E staining and immunohistochemistry(IHC) using cytokeratin antibody to detect metastatic tumor cells. RESULTS: The mean size of the primary tumor was 2.51cm in diameter and the mean number of the sentinel nodes was 1.59. The detection rate of the sentinel node was 94.4%(51/54). Among 35 patients with negative sentinel nodes on frozen section, 4 patients(11.4%) had tumor metastasis on both permanent serial H&E sections and IHC using cytokeratin. Out of the 31 patients with negative sentinel node by permanent serial section, 4 patients had tumor metastasis in nonsentinel axillary nodes. These results revealed that the sensitivity of the sentinel node biopsy was 83.3% and the negative predictive value to predict the axillary node status was 81.1%. The false negative rate of the sentinel node was 16.7% by the permanent H&E and IHC section and 33.3% by the frozen section. Especially, in casese with tumors loss than 2cm, the sunsitivity was 100% in frozen section as well as permanent section. CONCLUSION: A combination of preoperative lymphoscintigraphy and gamma probe-guided methods achieve high success rates in the identification of sentinel nodes. Multiple serial sections and IHC of the nodes are required to detect the micrometastasis of the sentinel nodes. The sentinel node biopsy is significantly accurate and may be considered as an alternative to replace the routine axillary node dissection, especially in T1 breast cancer patients.

Clinicopathological analysis of ductal carcinoma in situ(DCIS) and ductal carcinoma in situ with microinvasion / 한국유방암학회지

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.

Association of Tumor Angiogenesis with bcl - 2 Expression in Breast Cancer Patients / 대한암학회지

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.

Expression of c-erbB2 and HLA-A2 in Breast Cancer Patients / 한국유방암학회지

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.

Study for Mammographic Patterns of Korean Breast Cancer / 한국유방암학회지

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.