Treatment Outcome and Analysis of the Prognostic Factors of Ductal Carcinoma in situ Treated with Breast Conserving Surgery and Radiotherapy / 대한방사선종양학회지

PURPOSE: To evaluate the survival rate, local failure rate and patterns of failure, and analyze the prognostic factors affecting local relapse of ductal carcinoma in situ treated with breast conserving surgery and radiotherapy Materials and Methods: From June 1995 to December 2001, 96 patients with ductal carcinoma in situ treated with breast conserving surgery and radiotherapy were retrospectively analyzed. The operations were either local or wide excision in all patients, with an axillary lymph node dissection performed in some patients. Radiation dose to the whole breast was 50.4 Gy, over 5 weeks, with 1.8 Gy daily fractions, with additional doses (10~14 Gy) administered to the primary tumor bed in some patients with close (< or =2 mm) or positive resection margin. The median follow-up period was 43 months (range 12~102 months). RESULTS: The 5-year local relapse free survival and overall survival rates were 91 and 100% respectively. Local relapse occurred in 6 patients (6.3%). Of the 6 recurrences, one was invasive ductal cell carcinoma. With the exception of one, all patients recurred 2 years after surgery. There was no regional recurrence or distant metastasis. Five patients with local recurrence were salvaged with total mastectomy, and are alive with no evidence of disease. One patient with recurrent invasive ductal cell carcinoma will receive salvage treatment. On analysis of the prognostic factors affecting local relapse, none of the factors among the age, status of resection margin, comedo type and nuclear grade affected local relapse. Operation extent also did not affect local control (p=0.30). In the patients with close resection margin, boost irradiation to the primary tumor bed did not affect local control (p=1.0). CONCLUSIONS: The survival rate and local control of the patients with ductal carcinoma in situ treated with breast conserving surgery and radiotherapy were excellent. Close resection margin and boost irradiation to the primary tumor bed did not affect local relapse, but further follow-up with much more patients is needed.

Clinical Features of Invasive Ductal Carcinoma According to Histopathologic Classification

PURPOSE: Of the hypothetical models of the carcinogenesis of breast cancer, the horizontal progression is most acceptable at the present time. According to the hypothesis, there are genetically different pathways among pure invasive ductal carcinoma (IDC), non-high grade IDC with ductal carcinoma in situ (DCIS), and high grade IDC with DCIS. The purpose of this study is to determine if there is any heterogeneity in biological behavior among these three categories. METHODS: With reversed Black nuclear grade (RBNG) in IDC component and the association of DCIS, we divided 184 breast cancer patients, who had underwent curative operations, into three groups. The patients with pure IDC were included in Group 1, non-high grade (RBNG 1 and 2) IDC with DCIS in Group 2, and high grade (RBNG 3) IDC with DCIS in Group 3. And we retrospectively analyzed and compared three groups with mean age, menopausal status, T stage, N stage, the expression rate of ER, PR, p53, and c-erbB-2, and cumulative metastasis-free survival. RESULTS: The percentage of the postmenopausal patients was significantly smaller in Group 3 (14.0%, P=0.025) than Group 1 and 2 (36.1% and 30.6%). There were significantly higher expression rates of ER and PR in Group 2 with 78.3% and 68.3%, respectively (P=0.000 and P=0.030). The 5-year metastasis- free survival rate were 70.4% in Group 1, 85.2% in Group 3, and 87.5% in Group 2. The Log Rank test in Kaplan-Meier cumulative survival curve showed the statistically significant differences among three groups (P= 0.041). CONCLUSION: We can say that there would be clinical heterogeneity among three groups classified by histopathologic findings. To apply this classification to the multi-disciplinary therapeutic modality of breast cancer, further study using a new biologic marker, which is associated with invasiveness and metastagenicity and can discrminate the three categories of breast cancers in any kind of specimen biopised preoperatively, is needed.

Ductal Carcinoma In Situ (DCIS) of the Breast; Clinico-pathological Analysis, Expression of Molecular Markers, and Correlations between Known Prognostic Factors

PURPOSE: The improved availability of breast cancer screening, including mammography, has dramatically increased the detection rate of DCIS (ductal carcinoma in situ). However, there has been controversy regarding the clinico-pathological characteristics and optimal management of DCIS. This analysis was conducted in order to evaluate the clinico- pathological findings of DCIS, and any possible correlations between the known prognostic factors. METHODS: We analyzed 58 consecutive cases of DCIS, from 1990 to 1995, including data on the annual proportion of DCIS to total breast cancer cases, the clinico-pathological characteristics and the expressions of ER, PR, c-erbB-2 and p53. The median length of follow-up was 98.5 months. RESULTS: The proportion of DCIS was 8.8%, with progressive increases from 1990 to 1995. The mean age at diagnosis was 47.1 years, with the peak of prevalence seen in women aged 40~49 years. The most common presentation was a palpable breast mass in 28 (48.3%) cases, but 18 (31%) patients were asymptomatic. The mammographic findings demonstrated calcification in 75% and mass density in 59.6%. There was only 1 (1.8%) case of a bilateral lesion, and 5 (8.6%) of multifocal or multicentric lesions. Axillary lymph nodes were positive in 5.5% of the patients who underwent an axillary dissection. Breast conserving operations were performed in 8 (13.8%) cases. The frequencies of ER, PR, c-erbB-2 and p53, positivity, by immunohistochemistry were 52, 50, 55.1 and 30.6%, respectively. c-erbB- 2 immunoreactivity was found more often in DCIS with larger size, higher nuclear grade and negative ER and PR (P= 0.011, P=0.001, P=0.002, and P=0.006, respectively). There was a significant association between higher nuclear grade and negative ER and PR, and comedotype (P=0.001, P= 0.000, and 0.008, respectively). Although an invasive ductal carcinoma had developed in 5.4% of the contralateral breasts, there were no cases of systemic relapse, or disease-specific mortality, at the last follow-up.

Interval Breast Cancers: Comparisons with Screen Detected Cancers

PURPOSE: Although the screening with a mammography has been shown to reduce breast cancer mortality, it has limitations relating to its sensitivity and efficacy. Interval cancers are those that become symptomatic, and are detected between screening examinations. The success of a screening program in reducing the rate of mortality due to breast cancer relies on keeping the number of interval cancers at a minimum. This study was performed to review the mammographic features of interval cancers, and to compare their clinicopathological factors with those cancers detected by screening. METHODS: Of the 881 women who had operations for breast cancer performed between 1995 and 1999, we retrospectively analyzed the medical records and mammograms of 57 who received at least a mammogram before the diagnosis of their breast cancer. These patients were divided into an interval cancer group, who had symptoms, and a screen detected cancer group, who had not. The factors compared included the clinical, radiographic, histopathological, and immunohistochemical features. RESULTS: Interval cancers were more likely to have masses, than microcalcifications, in their mammographic features, and were more likely to be invasive and at a higher stage according to their histopathological features. The false negative rate was 48% for the screen detected cancers, and 35% for the interval cancers (P=0.414). HRT users had the higher false negative rate of 51.6% than the 26.9% for the nonuser (P=0.103). CONCLUSION: The interval cancers were found to be different from the screen detected cancers in terms of their radiological and pathological features. The standardization of screen interval, and additional magnification mammography, or ultrasonography may contribute to reduce false negative rates of mammography.

Nitric Oxide Synthase (NOS) Expression in Breast Cancer

PURPOSE: NO, a diatomic free radical, plays a diverse physiological and pathophysiological roles in the vascular, neuronal and immune systems. It is produced by nitric oxide synthase (NOS) which consists of three different isoforms. In this study we investigated NOS expression in 84 human breast carcinomas and its associations to other clinicopathological factors. METHODS: The immunohistochemical staining for NOS expression in 84 human breast carcinomas were performed and their medical records were reviewed retrospectively. RESULTS: iNOS expression in tumor cells was observed in 48.2% and eNOS expression was detected in 51.9%. iNOS expression in tumor cells has positive correlation with eNOS expression in tumor and is associated with iNOS expression in stroma and endothelial cells. Although iNOS expression in tumor cells has negative correlation with tumor size (P=0.047) and lymph node metastasis (P=0.002), it has no effects on 5 year overall and disease free survivals. iNOS expression in stroma also has negative correlation with tumor size (P=0.016) and nuclear grade (P=0.025). No significant correlation between eNOS expression and clinicopathological factors was observed but eNOS expression in tumor cells contributed to worse 5 year overall survivals (92.1% vs 77.0%) in marginal significance (P=0.053). CONCLUSION: These data suggest that iNOS expression in tumor may have an inhibitory effect in tumor growth and lymph node metastasis. These results may be further investigated.

Hyalinizing Trabecular Adenoma of Thyroid Gland

Hyalinizing trabecular adenoma of the thyroid gland is a distinctive benign epithelial lesion exhibiting a prominent trabecular arrangement and stromal hyalinization. We recently recognized a hyalinizing trabecular adenoma of the thyroid that displayed potentially misleading features of papillary and medullary carcinomas. However the immunohistochemical features, i.e. thyroglobulin-positive and calcitonin-negative as well as its trabecular arrangement and surrounding abundant hyaline materials confirmed our diagnosis.

Breast Cancer Screening of 51,170 Women

PURPOSE: The purpose of this study was to evaluate the efficacy of annual breast screening, which includes a mammography and a clinical physical examination. METHODS: From April 1995 to March 2000, we performed 51,170 annual clinical examinations and mammographies on 26,354 women, who wanted to undergo breast screening, at the breast center. Ninety-five breast cancers were detected during screening, and of these, only 76 breast cancers were operated on. The result were compared with 650 symptomatic breast cancers from the outpatient department (OPD). RESULTS: Of the 51,170 cases screened, the recall rate for further examination was 9.9% (n=5,066), and the biopsy rate was 2.1% (n=1,096). Ninety-five breast cancers were detected; a detection rate of 0.19%. Fourteen breast cancers were detected after more than 2 screening rounds. On the analysis of the medical audit data based on the screening mammographies, the positive predictive value, confirmed when a biopsy from a surgical consultation was recommended (PPV), was 8.6%. Further, 41 cases involving tumors found at stage 0 or I (54%). There were 25 cases of axillary lymph node metastasis (32.9%). These results were compatible with the ideal rates for medical audits, except for PPV and axillary lymph node metastases. The pathologic stages of the screened group were: 0, 22.4%; I, 31.6%; II, 40.8%; III, 5.2%, whereas those of the OPD group were 0, 3.4%; I, 27.4%; II, 52.8%; III, 15.5%, and IV, 0.8%. Early breast cancers were detected more frequently through screening than by the OPD (P<0.05). Breast conservation surgery was carried out on 32.9% (25 cases) from the screened group, but only 12.8% (83 cases) from the OPD group (P<0.05). CONCLUSION: Our breast cancer screening was properly performed. Further, these findings indicate that breast cancer screening using a clinical examination and a mammography is very effective in the early detection of breast cancer.

Usefulness of Frozen Section Examination of Core Needle Biopsy in the Breast Carcinoma

BACKGROUND: Core needle biopsy (CNB) is widely used as the initial sampling method for breast cancer. And because frozen section (FS) diagnosis is rapid and reliable, we studied the diagnostic agreement between the diagnosis of FS of CNB and final diagnosis after surgery to evaluate the diagnostic accuracy of the FS of CNB. METHODS: Of 409 patients who were preoperatively diagnosed by FS of CNB and who underwent final surgery from 1996 through 2000, 24 cases were found to be ductal carcinoma in situ (DCIS) and 385 cases invasive carcinoma (IC). The diagnoses of FS of CNB were compared with final diagnoses. RESULTS: The diagnostic accuracy of carcinoma is 63.6% for DCIS and 86.9% for invasive carcinoma. Five cases (1.2%) could not be diagnosed because of material insufficiency for diagnosis. Twenty two cases (5.4%) were diagnosed as benign on FS, among which 20 (90.9%) were misdiagnosed by sampling error. Twenty seven cases (6.7%) were deferred on FS, 4 of these cases were DCIS, 5 were invasive lobular carcinoma (ILC), the rest displayed low nuclear grades or marked freezing artifacts. CONCLUSIONS: The diagnostic accuracy of FS of CNB is very high except for cases of ILC and low grade DCIS. Considering the advantage of rapid evaluation, more definitive diagnosis, familiarity by pathologists and availability of ancillary study, FS of CNB is very useful method as the preoperative evaluation.

Characteristics of Breast Cancer in Women Undergoing Hormone Replacement Therapy / 한국유방암학회지

PURPOSE: Hormone replacement therapy (HRT) has been associated with an increased risk for breast cancer. Cancers in women who undergo HRT are often less advanced, and a lower mortality has been reported in those who use HRT vice nonusers. We sought to explain this by a comparison of indicators of tumor aggressiveness in patients who received HRT with those in patients who did not. METHODS: A population-based cohort of 370 postmenopausal women with breast cancer were interviewed for the use, type, and duration of HRT. Clinical variables and indicators of tumor aggressiveness (nuclear grade, hormone receptors, c-erb B2 overexpression, tumor size, lymph node) were analyzed. RESULTS: Breast tumors from 268 HRT patients were smaller (P=0.001), had less involved axillary lymph nodes (P=0.0), and had a lower overexpression of c-erb B2 (P=0.047) than the tumors from 102 non-recipients. These differences persisted after adjustments for age at diagnosis and screening with mammography by multiple logistic regression. No significant differences were observed in estrogen (ER) or progesterone receptor content (PR) or, nuclear grade. Neither the type of HRT (estrogen versus combination of estrogen and progesterone), nor the duration of HRT was not associated with the tumor size or with the involvement of lymph nodes. The use of HRT was significantly associated with a longer metastasis free survival in women with breast cancer (P=0.028), but was not associated with longer overall survival. The use of HRT was not significantly associated with longer overall survival or with a longer metastasis free survival after adjustment for T-stage, N-stage, age at diagnosis or screening mammography. CONCLUSION: The results indicate that breast cancer in women who receive HRT is biologically less aggressive than those without previous HRT. This may at least partly explain why breast cancer in HRT users has a more favorable clinical course.

Characteristics of Breast Cancer in Women Undergoing Hormone Replacement Therapy

PURPOSE: Hormone replacement therapy (HRT) has been associated with an increased risk for breast cancer. Cancers in women who undergo HRT are often less advanced, and a lower mortality has been reported in those who use HRT vice nonusers. We sought to explain this by a comparison of indicators of tumor aggressiveness in patients who received HRT with those in patients who did not. METHODS: A population-based cohort of 370 postmenopausal women with breast cancer were interviewed for the use, type, and duration of HRT. Clinical variables and indicators of tumor aggressiveness (nuclear grade, hormone receptors, c-erb B2 overexpression, tumor size, lymph node) were analyzed. RESULTS: Breast tumors from 268 HRT patients were smaller (P=0.001), had less involved axillary lymph nodes (P=0.0), and had a lower overexpression of c-erb B2 (P=0.047) than the tumors from 102 non-recipients. These differences persisted after adjustments for age at diagnosis and screening with mammography by multiple logistic regression. No significant differences were observed in estrogen (ER) or progesterone receptor content (PR) or, nuclear grade. Neither the type of HRT (estrogen versus combination of estrogen and progesterone), nor the duration of HRT was not associated with the tumor size or with the involvement of lymph nodes. The use of HRT was significantly associated with a longer metastasis free survival in women with breast cancer (P=0.028), but was not associated with longer overall survival. The use of HRT was not significantly associated with longer overall survival or with a longer metastasis free survival after adjustment for T-stage, N-stage, age at diagnosis or screening mammography. CONCLUSION: The results indicate that breast cancer in women who receive HRT is biologically less aggressive than those without previous HRT. This may at least partly explain why breast cancer in HRT users has a more favorable clinical course.

Expression of p53 Protein and Ki-67 in Atypical Ductal Hyperplasia, Ductal Carcinoma in Situ, and Microinvasive Ductal Carcinoma of the Breast

Mutation of the p53 gene is one of the most common genetic alterations in invasive breast carcinoma. However, it is unclear that the mutation usually occurs in noninvasive breast lesions. It might be expected that there is a correlation between histologic progression of breast lesions and proliferative rate. We investigated the expression of p53 protein and Ki-67 labelling index (LI) using immunohistochemistry in 16 ductal carcinoma in situ with microinvasion (DCIS-Mi), 56 DCIS, 15 atypical ductal hyperplasia (ADH), and 7 intraductal hyperplasia (IDH). Expression of p53 protein was detected in 33.9% of DCIS and 56.3% of DCIS-Mi and was confined exclusively in Van Nuys DCIS group 2 and 3. In ADH and IDH, no expression of p53 protein was found. There was no significant correlation between Van Nuys DCIS groups and Ki-67 LI. In conclusion, p53 mutation may be involved in the neoplastic progression from ADH to DCIS and is directly related to high nuclear grade and associated necrosis of DCIS.

Telomerase Activity in Human Breast Tumors

BACKGROUND: Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto the ends of chromosomes, thereby preventing the replication-dependent shortening of those ends. Telomerase activity is detected in a wide range of cancers of various tissues, and its expression may be a critical step in tumor progression. Our objective was to determine if detection of telomerase activity may be an indicator for diagnosis of breast cancer and if any association exists between telomerase activity and prognostic factors of breast cancer. METHODS: Using a polymerase chain reaction-based telomerase activity assay, we examined telomerase activity in 30 breast cancer specimens (2 ductal carcinoma in situ, 28 invasive ductal carcinoma), 25 benign lesions (14 fibroadenomas, 11 fibrocystic diseases), and 24 normal breast tissues (13 adjacent to malignancy, 11 adjacent to benign lesion). RESULTS: Among surgically resected samples, telomerase activity was detected in 23 (77%) of 30 breast cancers. While telomerase activity was not detected in any of the 11 specimens of fibrocystic disease and the 11 normal tissues adjacent to benign lesion, surprisingly low levels of telomerase activity were detected in 5 (36%) of the 14 fibroadenomas and 1 (7%) of the 13 normal tissues adjacent to malignancy. There was no significant difference in expression of telomerase among prognostic factors of breast cancer. CONCLUSIONS: In summary, telomerase activity may be useful in the diagnosis of breast cancer. We found no correlation between telomerase activity and stage, tumor size, or LN status. Mechanisms of telomerase expression are still under investigation; therefore, the significance of telomerase expression in malignant tumors and their progression remains to be determined.

Telomerase Activity in Human Breast Tumors / 한국유방암학회지

Telomerase is a ribonucleoprotein enzyme that synthesizes telomeric DNA onto the ends of chromosomes. thereby preventing the replication-dependent shortening of these ends. Telomerase activity is detected in a wide range of cancers of various tissues, and its expression may be a critical step in tumor progression. Our objective was to determine if detection of telomerase activity may be an indicator for diagnosis of breast cancer and any association between telomerase activity and prognostic factors of breast cancer. Using a polymerase chain reaction-based telomerase activity assay, we examined telomerase activity in 30 breast cancer specimens (2 ductal carcinoma in situ, 28 invasive ductal carcinoma), 25 benign lesions (14 fibroadenomas, 11 fibrocystic diseases) and 24 normal breast tissues (13 adjacent to malignancy, 11 adjacent to benign lesion). Among surgically resected samples, telomerase activity was detected in 23 (77%) of 30 breast cancers. While telomerase activity was not detected in any of 11 specimens of fibrocystic disease and 11 adjacent normal tissues to benign lesion, surprisingly low levels of telomerase activity were detected in 5 (36%) of 14 fiboadenomas and 1 (7%) of 13 adjacent normal tissues to malignancy. There was no significant difference in expression of telomerase among prognostic factors of breast cancer. In summary, telomerase activity in breast cancer may be useful in diagnosis of breast cancer. We found no correlation between telomerase activity and stage, tumor size or LN status. Mechanisms of telomerase expression are still under investigation; therefore, the significance of telomerase expression in malignant tumors and their progression remains to be determined.

Breast-Conserving Surgery With or Without Radiation Therapy for Early Breast Cancer

Breast conserving surgery (BCS) with radiation therapy (RT) has been considered an alternative to a radical mastectomy in the surgical treatment of early breast cancer. Breast-conserving therapy (BCT) can achieve a more favorable cosmetic outcome than a mastectomy in patients with early breast cancer. However, it is widely recognized that RT following BCS is an impediment to improve the cosmetic outcome of a BCT-treated breast. If the local recurrence (LR) rate is acceptable and LR can be controlled with salvage surgery, an appropriate conservative surgical procedure without RT will be a reasonable option for some patients with early breast cancer. Between 1990 and 1996, 60 patients were enrolled in a retrospective study to examine whether or not RT could be avoided following conservative surgery in patients with early breast cancer. There was no significant difference in local recurrence rate between the RT and the non-RT groups (6.3% vs 10.7%). The characteristics of suitable BCS without RT would be negative axillary lymph-node metastasis, low nuclear grade, a 1 cm negative resection margin and no lymphatic vessel involvement. In conclusion, breast-conserving surgery without RT is a reasonable option for some patients with early breast cancer.

Needle Localization Biopsy of 546 Nonpalpable Breast Lesions

A retrospective review of 546 consecutive female patients who had undergone mammographically controlled needle localizations was performed to assess the effectiveness of the technique and to analyze the number and the characteristics of the criteria malignancies found in this group. Localization biopsy was recommended if one or more of the following criteria were present: evidence of a mass, microcalcifications, parenchymal distortion, and/or spiculation. Of those 546 patients who had undergone specimen mammography after needle localization biopsy, a lesion was detected on 544 cases and missed in 2 cases(0.3%). Fifty-five cancers were detected(10.1%) Histologically, the cancers included 23 invasive and 32 in-situ tumors. The predominant histologic cell type was ductal in origin with only three having lobular characteristics. Postoperative pathologic findings of the lymph nodes showed 3 of the 55 were positive for metastases. In summary, the technique of preoperative needle localization in this series had a 99.7% success rate. The cancer detection rates for a 'mass with a microcalcification', a 'microcalcification', and a 'mass' were 17.0, 14.0, and 5.1% respectively. As a conclusion, needle localization biopsy is a safe and effective method for definitely diagnosing nonpalpable breast lesions.

Needle Localization Biopsy of 546 Nonpalpable Breast Lesions

A retrospective review of 546 consecutive female patients who had undergone mammographically controlled needle localizations was performed to assess the effectiveness of the technique and to analyze the number and the characteristics of the criteria malignancies found in this group. Localization biopsy was recommended if one or more of the following criteria were present: evidence of a mass, microcalcifications, parenchymal distortion, and/or spiculation. Of those 546 patients who had undergone specimen mammography after needle localization biopsy, a lesion was detected on 544 cases and missed in 2 cases(0.3%). Fifty-five cancers were detected(10.1%) Histologically, the cancers included 23 invasive and 32 in-situ tumors. The predominant histologic cell type was ductal in origin with only three having lobular characteristics. Postoperative pathologic findings of the lymph nodes showed 3 of the 55 were positive for metastases. In summary, the technique of preoperative needle localization in this series had a 99.7% success rate. The cancer detection rates for a 'mass with a microcalcification', a 'microcalcification', and a 'mass' were 17.0, 14.0, and 5.1% respectively. As a conclusion, needle localization biopsy is a safe and effective method for definitely diagnosing nonpalpable breast lesions.

Evaluation of Mass Screening for Thyroid Cancer

Mass screening for detecting both thyroid and breast cancer in adult women was carried out in Samsung Cheil Hospital between March 31, 1996, and March 31, 1997. The total number of subjects during those 13 months was 3869. At first, the screening was by inspection and palpation using experienced surgeons. Thyroid abnormalities were found in 183 subjects through physical examination but thyroid nodules were identified by thyroid sonography in only 170 patients who were required to undergo a cytologic examination (FNAB). The total number of thyroid cancer cases detected was 23. The detection rate was 0.59%. In contrast, 8 cases of breast cancer were discovered during the same screening, with a detection rate of 0.21%. The size of the thyroid tumor was 2 cm or less in 20 patients (87%). The thyroid cancers detected by mass screening were discovered at an earlier stage and will show a better survival rate. As thyroid cancer can be found at an earlier stage by mass screening, the program is useful for the early detection and early treatment of thyroid cancer.

Correlation of Heregulin mRNA and Her-2/neu Protein Expression with Node Metastasis and DNA Ploidy Pattern in Human Invasive Breast Carcinoma

The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.

Breast Cancer Screening of 13,791 Women by Physical Examination and Mammography

This study is to clarify the efficacy of breast cancer screening by physical examination and mammography and to compare the diagnostic outcome of breast cancers detected by screeening with that of breast cancers found at out-patient clinic. Between March 1995 and July 1996, A total of 13,791 women were screeened for breast cancer annually by physical examination and mammography at Samsung Cheil Hospital Breast Center and 20 breast cancers were detected. In the same period, another 166 breast cancers were found at out-patient clinic. These two groups of breast cancers were analyzed and compared. Of those 13,791 screened women, the recall rate for further examination was 9.8%(n=1,350) and the biopsy rate was 1.06%(n=146) respectively. Twenty breast cancers were detected so that the breast cancer detection rate was 0.15%. T-stages of screened group were T0;25%, T1;55%, T2;15% and T3;5%, while those of out-patient clinic cases were T0;4.8%, T1;43.4%, T2;44.6%, T3;7.2%.(p<0.05). Axillary lymph node metastasis was negative in 80% of screened group but in 59% of out-patient clinic cases.(p<0.05). Pathological stages of screened group were; stage0;25%, stageI;40%, stageII;35% and those of out-patient clinic cases were stage0;4.8%, stageI;24%, stageII;56%, stageIII;14.4%, stageIV;1.2%(p<0.05). Early breast cancers were significantly more frequent in the patients detected by screening at breast center than those of out-patient cilinic cases. The breast conservation surgery was done in 40% of screened group but only in 12.7% of out-patient clinic cases(P=0.00029).This study indicated that the efficacy of breast cancer screening by physical examination and mammography was significant for the early detection of breast cancers.

Bilateral Breast Cancer

Bilateral breast cancer is not a common clinical problem, and its occurance is not suprising in this paired organ. Bilateral breast cancer is categorized as synchronous or metachronous. We propose to evaluate clinical and biological characteristics in bilateral breast cancer. Previous cancer in one breast is the strongest known risk factor for cancer to develop in the second breast, and a young age at dignosis of a breast cancer and lobular type of tumor are additional risk factors related to bilaterality. Seventeen cases of bilateral breast cancer have been admitted to the department of General surgery, Samsung Cheil general Hospital from 1980 till 1995. We report the analysis of these cases with the references. The incidence of bilateral breast cancer among all case of total breast cancer was 2.1%(17/827). Synchronous breast cancer was 3 cases(0.4%) and metachronous breast cancer was 14cases (1.7%). The median age was 41 years. The mean age at diagnosis of the primary tumor in the metachronous group was 40 years. Among metachronous cases, the mean interval between the treatment of the primary cancer and the detection of secondary cancer was 37months. The clinical stage was 0-I in 12%, II in 50%, III in 32%, and IV in 6% of tumors. The majority of patients (88%) were clinically node positive. Out of a total of 34 tumors, the clinical tumor size Tis-T1 in 8 tumors, T2 in 21 tumors, and T3 in 5 tumors. Histopathologic type of the pimary tumor was the same with the second in 70%(12/17). The location of secondary breast cancer was in the upper outer quadrant in 9 cases, and in the upper medial quadrant of breast in 2 cases. The premenopausal primary cancer was in 50% of the patients, and postmenopausal primary cancer was in 50% of patients for whom this information was available. Median survival period was 57 months, and 5 year survival rate was 80%. Bilateral breast cancers have similar biological features to unilateral breast cancer more freqently than would be predicted by chance alone. The similarity in clinical aspects of unilateral and bilateral breast cancers should be considered in clinical management of patients with breast cancer. Further investigation is required to know these similaritics and differences between unilateral and bilateral breast cancer.