Clinicopathologic Features and Outcomes of Metaplastic Breast Carcinoma: Comparison with Invasive Ductal Carcinoma of the Breast

PURPOSE: Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic characteristics and outcomes in comparison with invasive ductal carcinoma (IDC). MATERIALS AND METHODS: We reviewed the data of 29 patients with MBC and 4,851 patients with IDC, who received surgery at Yonsei University Severance Hospital between 1980 and 2008. Various clinicopathologic features, recurrence free, and overall survival were investigated and compared to each other. RESULTS: Stage IV cases at diagnosis were more common in MBC (10.3%) than in IDC (0.9%). The incidence rates of triple negative breast cancer (TNBC) were significantly higher in MBC (84.0%) than in IDC (20.1%). Larger tumors (>2 cm) and lower tendency of axillary metastasis were frequently observed in MBC. Only one of 24 preoperative core needle biopsies (CNB) correctly diagnosed MBC. There was no significant difference in survival between the two groups. CONCLUSION: MBC was characterized by a higher incidence of TNBC, larger tumor size, and lower tendency of axillary metastasis, and was difficult to diagnose with CNB. Although the incidence of stage IV disease at diagnosis was higher in MBC, the survival rates of stage I-III were comparable to those of IDC.

Clinicopathological Characteristics of Mucinous Carcinoma of the Breast in Korea: Comparison with Invasive Ductal Carcinoma-Not Otherwise Specified

Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.

The Prognostic Significance of Survivin Expression in Breast Cancer / 한국유방암학회지

PURPOSE: Survivin is a member of the inhibitors of apoptosis family. It has recently comes into the limelight as a promising tumor marker, but many previous reports have shown controversial results regarding the significance and prognostic value of a survivin expression. In this study we determined the correlation between the survivin expression and the conventional prognostic markers and we also investigated the outcomes according to the localization of the survivin expression. METHODS: Tissue microarray (TMA) blocks were made with formalin-fixed paraffin-embedded tissues from 185 breast cancer patients and the immunohistochemical staining was done using an anti-survivin antibody. Among these, 157 patients were available for a survivin expression. The conventional clinicopathologic features and overall survival were correlated with the localization of the survivin expression. RESULTS: Survivin was expressed in 101 breast cancers (64.3%). A higher cytoplasmic survivin expression were noted in the older group (p=0.003), in the node-negative cancers (p=0.012), in the earlier tumor stages (p=0.012) and in the cancers that had not been treated with adjuvant chemotherapy (p=0.014). On the contrary, a higher nuclear survivin expression was inversely correlated with an estrogen expression (p=0.006) and a progesterone receptor (p=0.043) expression. In terms of survival, a cytoplasmic expression was associated with improved overall survival (p=0.01) but a nuclear survivin expression was correlated with unfavorable overall survival (p=0.002). A high cytoplasmic to nuclear ratio of survivin was associated with improved overall survival (p=0.001) conversely, increased nuclear to cytoplasmic survivin ratio was correlated with unfavorable overall survival (p<0.0001). Multivariate analysis revealed that nuclear survivin expression (p=0.001) and high nuclear to cytoplasmic survivin ratio (p=0.012) were independent predictor of overall survival. CONCLUSION: Survivin is frequently expressed in primary breast cancer. A cytoplasmic survivin expression is a good prognostic predictor for patients with axillary node negative early breast cancers and a nuclear survivin expression is a worse independent predictor of overall survival for patients with axillary node positive breast cancers.

Clinical Analysis of Medullary Carcinoma of the Breast / 한국유방암학회지

PURPOSE: Medullary carcinoma of the breast is a variant of breast cancer characterized by the histologic appearance of poorly differentiated cells surrounded by a prominent lymphoid stroma. Medullary carcinoma has been reported to carry a prognosis better than other invasive breast carcinomas, but it is frequently overdiagnosed due to the difficulty in diagnosis. The aim of this study was to assess the clinical manifestations and outcome of medullary carcinoma of the breast. METHODS: We reviewed the data of 91 patients diagnosed with medullary carcinoma and 3,743 patients with invasive ductal carcinoma, not otherwise specified (NOS) from January 1980 to December 2005 at Yonsei University Severance Hospital. The clinicopathologic features, disease free survival (DFS) and overall survival (OS) for patients with medullary carcinoma were compared with those of the NOS patients. RESULTS: With reviewing the pathologic slides, 69 (75.8%) patients had findings compatible with typical medullary carcinoma (TMC) and the remaining 22 (24.2%) patients were reclassified as atypical medullary carcinoma (AMC). Early stage cancer was more frequent at medullary carcinoma and lymph node positive cancer was less frequent at medullary carcinoma. The expression of ER/PR was positive in either the TMC (18.9%/16.2%) and AMC (15.0%/20.0%) as compared to the NOS (63.2%/57.2%), and the difference was significant (p<0.001). In contrast, the HER-2/neu expression rate was significantly higher in the TMC (47.4%) and AMC (45.5%) than in the NOS (28.3%, p=0.001). The 10-year disease free survival and 10-year overall survival of the atypical medullary carcinoma patients (67.8%, 77.8%) were in fact similar to the NOS carcinoma patients (68.3%, 74.7%). There was significant difference in 10-year disease free survival and 10-year overall survival between the TMC (77.8%, 86.0%) and NOS carcinoma (68.3%, 74.7%) patients (p=0.002, p=0.006). CONCLUSION: The clinical outcome of typical medullary carcinoma is favorable in spite of its aggressive pathologic features and it differs from atypical medullary carcinoma. For precise prediction of prognosis of medullary cancer, we should apply strict criteria for the diagnosis of subtype with medullary features.

Ectopic Endometriosis of the Extra-pelvic Cavity

PURPOSE: Endometriosis is the heterotropic occurrence of island of endometrial glands and stroma outside of uterus. It common occurs in pelvic cavity, but rarely at the ectopic area of extra-pelvic cavity. The aim of this study was to evaluate the clinical characteristics of extrapelvic endometriosis in order to help diagnosis and treatment. METHODS: Between January 2001 and June 2007, 22 patients who underwent surgery and was diagnosed as ectopic endometriosis of extra-pelvic cavity at Bundang CHA hospital were retrospectively reviewed with medical records and a telephone interview. RESULTS: All cases were women in their reproductive age, with a median age of 33 years (range 24~49 years). 17 of 22 cases were endometriosis in the scarring tissue of prior caesarean section wound on abdomen. 1 case in vaginal orifice on episiotomy wound of perineum, 1 case in femoral ring area and 3 cases in appendix. All patients except endometriosis of appendix, were presented with mass, pain and symptoms almost associated with menstruation. 18 of 22 cases were suspected of having extra-pelvic endometriosis due to their specific clinical features, 4 cases were suspected of hernia and acute appendicitis. All patients were treated with surgery. None has revisited to clinics due to recurrence. CONCLUSION: Women who have mass or lump in surgical scar and symptoms associated with menstruation period should be suspected of having endometriosis. Endometriosis of surgical scaring tissue should be treated by wide local excision to prevent local recurrence.

The Prognostic Factors for Tumor Metastasis to Bone from Breast Cancer and Survival for Breast Cancer Patients after Bone Metastasis / 한국유방암학회지

PURPOSE: Bone is the most common site of breast cancer metastasis. The aim of this study is to identify the subgroup of patients who have high risk of bone metastasis and we evaluate the prognostic factors of overall survival after bone relapse. METHODS: A total 2,785 of primary breast cancer patients who were treated from January 1980 to December 2001 were included in this analysis. All the patients received radical surgery at the time of diagnosis. We retrospectively collected the clinico-pathologic data (age, tumor size, axillary lymph node status, histologic grade, steroid hormone receptor status, and disease-free interval after primary surgery). Definitive radiologic evidence of bone metastases by plain X-ray or whole body bone scan during follow-up was defined as bone metastases. We analyzed the relationship between the clinicopatholgic factors and the risk of bone metastases and the overall survival after bone relapse. RESULTS: During follow-up, 256 patients (9.3%) experienced bone metastasis. By multivariate analysis using Cox's model, age less than 35 years (p<0.001, risk ratio [RR]; 2.467, 95% confidence interval [CI]; 1.619-3.759), large primary tumor more than 2 cm (p=0.005, RR; 1.911, 95% CI; 1.222-2.988), positive axillary node (p<0.001, RR; 2.798, 95% CI; 1.867-4.195), and a high histologic grade (p=0.046, RR; 1.631, 95% CI; 1.008-2.640) were significantly associated with frequent bone metastases. The 10 years survival rate after bone metastasis was 26.9%. Disease free interval less than 2 years (p<0.001, RR; 3.453, 95% CI; 2.382-5.005) and hormone receptor status (p=0.003, RR; 1.791, 95% CI; 1.218-2.635) were independently associated with poor overall survival after bone relapse. CONCLUSION: We concluded that a shorter disease-free interval after definitive surgery and hormonal receptor status of the primary tumor are independent prognostic factors of overall survival after bone metastasis. These results show that a tailored strategy is needed for the treatment of patients with bone metastases.

Clinicopathological Characteristics and Prognostic Factors of Papillary Carcinoma of the Breast / 한국유방암학회지

PURPOSE: Papillary carcinoma of the breast is a rare disease and accounts for 1-2% of all breast cancers. Because of its rarity, there have been no reports regarding prognostic factors of papillary carcinoma of the breast. The aim of this study was to review the clinicopathological factors and treatment modalities of papillary carcinoma of the breast and to evaluate the relationship between these factors and survival rates. METHODS: We retrospectively analyzed 31 patients diagnosed with papillary carcinoma of the breast from January 1986 to December 2005. RESULTS: The mean age of the patients was 53.5 yr. The most common symptom was a palpable mass (n=27). The mean size of a tumor was 3.5 cm and 41.9% of the patients were categorized as T2. Eighteen patients had node negative breast cancer. According to the TNM stage, there were 5, 5, 16 and 2 patients with stage 0, I, II and III disease, respectively. Expression of estrogen receptor and progesterone receptor were positive in 80.8% and 69.2% of the patients, respectively. Twenty-three patients underwent mastectomy and eight patients underwent breast-conserving surgery. Fourteen patients received chemotherapy, 20 patients received hormone therapy, and 10 patients received radiotherapy. The 10-yr disease-free survival rate and 10-yr overall survival rate were 74.9% and 86.1%, respectively. Axillary lymph node negative and an age under 50 yr were statistically significant factors in 5-yr disease-free survival and in 5-yr overall survival, respectively. CONCLUSION: Papillary carcinoma of the breast showed a favorable outcome. Lymph node status and age were statistically significant factors for survival rates. The tumor size and stage had a relation with the survival rate, although the relation was not statistically significant.

Clinicopathological Characteristics of Male Breast Cancer

PURPOSE: To investigate clinicopathological characteristics and outcomes of male breast cancer (MBC). PATIENTS AND METHODS: We retrospectively analyzed the data of 20 MBC patients in comparison with female ductal carcinoma treated at Yonsei University Severance Hospital from July 1985 to May 2007. Clinicopathological features, treatment patterns, and survival were investigated. RESULTS: MBC consists of 0.38% of all breast cancers. The median age was 56 years. The median symptom duration was 10 months. The median tumor size was 1.7cm, 27.8% showed node metastasis, and 71.4% were estrogen receptor positive. All 20 cancers were arisen from ductal cells. No lobular carcinoma was found. The incidence of stages 0, I, II, and III in patients were 2, 10, 4, and 3, respectively. All patients underwent mastectomy. One with invasive cancer did not receive axillary node dissection and stage was not exactly evaluated. Adjuvant treatments were determined by pathologic parameters and stage. Clinicopathological parameters and survival rates of MBC were comparable to those of female ductal carcinoma. CONCLUSION: The onset age of MBC was 10 years older and symptom duration was longer than in female patients. No difference in outcomes between MBC and female ductal carcinoma suggests that the biology of MBC is not different from that of females. Therefore, education, an appropriate system for early detection, and adequate treatment are necessary for improving outcomes.

Prognostic Value for the S-phase fraction in T1 T2, Node Negative Breast Cancer / 한국유방암학회지

PURPOSE: To evaluate the prognostic value of the S-phase fraction (SPF) and the correlation with other clinicopathologic factors in node negative breast cancer. METHODS: From 1995 to 1998, seventy one breast carcinoma tumors with T1-2N0M0 staging were prospectively sampled as fresh tumors for flow cytometric DNA analysis. We determined the nuclear DNA content, and the SPF was calculated from DNA histograms. We evaluated the relationship between the SPF and other clinicopathologic factors (age, tumor size, tumor grade and, steroid receptor status). The five year distant relapse free survival (DRFS) and overall survival (OS), according to the SPF, were determined. RESULTS: The SPF ranged from 0.1 to 50.9% (median: 13.4%). The SPF was dichotomized using the median value to divide patients into 38 patients (53.5%) having tumors with the low SPF and 33 patients (46.5%) having tumors with the high SPF. The patient's age and the tumor size were not significantly associated with the SPF. High SPF was associated with high tumor grade, but this did not reach statistical significance. There was a significant correlation between high SPF and estrogen receptor negativity; 34.4% of ER positive tumor had high SPF, whereas 58.3% of ER negative tumor had high SPF(p = 0.042). The mean follow up duration was 65.0 months (median: 62.3). Among 71 patients, there were 4 (5.6%) cases of local recurrence, 7 (9.9%) cases of systemic recurrence and 10 (14.1%) cases of disease related death. The patients with high SPF showed a poorer 5 years DRFS and OS than did the patients with low SPF (87.9% vs. 91.2%; 80.4% vs. 94.5%, respectively), but the difference had no statistical significance. CONCLUSION: The present data was insufficient to use SPF information for the selection of the type of adjuvant therapy, but SPF is a promising prognostic factor for node negative breast cancer. Further study with a sufficient number of patients is needed and this should lead to a better understanding of SPF in node negative breast cancer.

Prognostic Factors in Axillary Lymph Node Negative Breast Cancer / 한국유방암학회지

PURPOSE: With the increase of early breast cancer patients, the number of node negative breast cancer patients is also on the rise. However, reports show that there is a 20~30% recurrence in node negative breast cancer. Thus, we have attempted to determine the prognostic factors that may affect recurrence and relapse free survival. METHODS: From January, 1980, to June, 1999, 1110 node negative breast cancer patients who underwent curative surgery at the Severance Hospital, Yonsei University College of Medicine, were selected. A retrospective study was done to determine the effects of factors, such as operation method, age, size, type, histologic grade, intraductal components, ER, PR, c-erbB-2, number of lymph nodes removed, adjuvant chemotherapy, hormonal therapy and radiation therapy. RESULTS: The mean age was 47.2 years. The median follow- up period was 88 months. Recurrence occurred in 161 patients. Locoregional recurrence occurred in 64 patients, and systemic recurrence in 129 patients, while 32 patients had both. The 5 years overall survival rate was 93.3%. The rate of locoregional recurrence for a 10 year-period was significantly lower in the mastectomy group compared with that in the breast conservation therapy group (94.7% vs 79.6%, P=0.000). No other prognostic factors except the age affected in locoregional recurrence. There was less systemic recurrence in patients with the age greater than 35, with the histologic grade I, and with the intraductal components greater than 20%. Thus, 10-years distant relapse free survival rates were 87.4% vs 79.8% (P=0.039), 93.5% vs 85.5% (P=0.024), and 94.4% vs 82.0% (P=0.007), respectively. There was no statistical significance in the other prognostic factors that influence systemic recurrence. CONCLUSION: The patients' age was determined to be an independent prognostic value in the lymph node negative breast cancer. The histologic grade and intraductal components showed to have significance as prognostic factors for systemic recurrence.

Mitogen-activated Protein Kinases Activities and c-erbB-2 Expression in Breast Cancer Carcinogenesis and Progression

PURPOSE: Increased level mitogen-activated protein kinase (MAPK) and activation of MAPK have been reported in human breast cancers, especially in breast cancers with HER2/neu overexpression. To understand the relationship between the MAPK protein expressions and other clinico-pathological parameters, we examined the status of MAPKs in 20 breast cancers compared to those of paired normals. METHODS: A total of 20 breast cancers and paired normal breast tissues were included in this study. Tissues were obtained at the operation room and stored at -80degrees C. Tissue proteins were extracted and the concentration was determined by Bio-Rad protein assay method. Western blot analysis were performed to determine the level of MAPKs expressions using 100 ug of tissue protein in 8%, 10%, or 12% sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). MAPK assays were carried out by a non-radioactive method developed by Cell Signaling Tech. as recommened by the manufacturer. Clinico-pathological information was provided from the Breast Cancer Registry of Department of Surgery, Yonsei University College of Medicine. RESULTS: The levels of MAPKs were higher in 95% of breast cancers compared to those of paired normals. The levels of ERK1/2 were significantly higher in cancer tissues compared to paired normals but the activated forms were not. The levels of JNK, p38, and MKP1 proteins were significantly increased in the cancer tissue compared to the paired normals. The levels of ERK1/2 and activated ERK1/2 proteins were not different between tumor stages. There were no significant differences of the levels of ERK1/2 and activated ERK1/2 proteins between HER2-negative and HER2- positive cancers. There were significantly higher levels of activated ERK1/2 proteins in ER-positive cancers than those in ER-negative cancers (P<0.05). CONCLUSION: The levels of MAPKs, but not the activated forms, seem to be increased in breast cancer tissues compared to those of paired normals. The levels of activated MAPKs seem to be associated with estrogen receptor expression in cancer tissues.

Expression of Estrogen Receptor-beta mRNA in Various Mammary Tissues / 한국유방암학회지

PURPOSE: Estrogen signal transduction plays very important roles in both normal mammary development and neoplastic progression. Since the discovery of estrogen receptor-beta (ER-beta) there have been many controversial reports on the role of ER-beta in breast carcinogenesis and progression, and prognostic implications. ER-beta mRNA levels were investigated in various mammary tissues in order to verify the role of ER-beta expression in breast carcinogenesis. METHODS: Using messenger RNA (mRNA) in situ hybridization, we examined ER-beta expression in 60 paired normal and cancer tissues, 11 paired normal and benign breast tumor tissues, and 10 metastatic lymph nodes. We determined the intensity and extent (proportion of cells with positive hybridization) of the mRNA hybridization signals and gave scores 0 to 3; no hybridization (0), minimal (1), moderate (2), and strong (3) by the hybridization intensity and no hybridization (0), hybridization in less than 10% of cells (1), 10~50% (2), and more than 50% of cells (3) by the proportion of positively hybridized cells. Chi-square test, independent t-test or one-way ANOVA test was used for the statistical analysis and differences were considered to be significant with a p-value of less than 0.05. RESULTS: There was no statistically difference in ER-beta expression between normal and benign mammary tissues. ERbeta expression was significantly decreased in breast cancer and metastatic lymph node tissues compared with normal mammary and benign breast tumor tissues (P<0.01). The intensity and extent of ER beta expression were also significantly lower in breast cancer and metastatic lymph node tissues than in the normal mammary and benign breast tumor tissues (P<0.01). In cases of positive hybridization, the sum of scores of intensity and area were also significantly higher in normal and fibroadenoma tissues than in cancer or metastatic lymph nodes (P<0.01). CONCLUSION: ER beta transcription decreases in the process of breast cancer development, which suggests a protective role of ER beta in breast carcinogenesis.

The Pattern of Systemic Failure and Factors Influencing on the Outcome after Distant Metastastasis in Breast Cancer / 한국유방암학회지

PURPOSE: Systemic failure after intial treatment of breast cancer is the most troublesome issue. To investigate the factors influencing on the outcome of metastatic breast cancer, this study was designed. METHODS: Two hundred sixty-seven breast cancer patients with distant metastasis after initial treatment were included for this study. The patients showing confined metastasis to the ipsilateral supraclavicular lymph node, were excluded. Preferred sites of metastasis, intervals to distant metastasis, survival rates after systemic failure were investigated in association with clinico-pathological parameters. Student ttest, chi-square test and log-rank test were used for statistical analysis. RESULTS: Patient age ranges from 20 to 71 years of age (mean 44.9). Forty-eight patients (18%) were initially included in stage 0 or I, 137 (51%) in stage II, and 82 (31%) in stage III. The preferred sites of metastasis were bone (47%), lung (29%), liver (9%), brain (8%) and multiple organs (4%) in descending order. Initial pathologic stage (P<0.001) and lymph node metastasis (P=0.016) were associated with the interval to distant metastasis, but not the tumor size (P= 0.246). Poor survival after systemic failure was associated with metastasis to the multiple organs or to liver (P<0.001), with no treatment after failure (P<0.001), and with failure within 3 years after initial treatment (P=0.056) CONCLUSION: Bone is the most prevalent metastatic site of breast cancer. Axillary lymph node status, especially the number of involved nodes, was associated with shorter disease free survival after initial treatment, which suggests that it might be a predictor of micrometastasis and a marker for an aggressive systemic treatment. Hepatic metastasis and metastasis to multiple organs was a poor prognostic marker of metastatic breast cancer. An aggressive systemic treatment after systemic failure might improve the survival.

Anti-HER2/neu Peptide Producing Vector System for Biologic Therapy - Is It Possible to Mass-produce the Peptide?

A humanized monoclonal antibody against HER2 has been using in a clinical setting and has been shown to possess therapeutic properties. A mimetic peptide against HER2 was also reported to bind to the HER2 receptor with some therapeutic potential. Based on a previous report and the sequence of Herceptin, we designed oligonucleotides of anti-HER2 mimetic peptides, named V2 and V3 peptides, in order to develop a peptide- producing vector system for biologic therapy against HER2- overexpressing cancers. We also adopted the sequence of a previously reported mimetic peptide, V1 (Park BW et al. Nat. Biotechnol, 2000, 18: 194-198), as a reference peptide. We examined the effects of the V2 and V3 peptides against the HER2-overexpressing cell lines, SK-BR-3 and T6-17. Transient transfection of the construct expressing V1 and V2 inhibited cell proliferation in HER2-overexpressing cell lines by 20 - 30%, but had no effect on the HER2-negative NIH3T3 cells. The proliferation inhibition shown by V2 was slightly better than that shown by V1. Recombinant peptides V2 and V3 were produced on a large scale in an E. coli system, and the V2 peptide showed anti-HER2-specific tumor cell proliferation inhibition of 10% to 30%. Current results suggest that anti-HER2 mimetic peptides, overexpressed by a constitutive promoter or produced in an E. coli system, could specifically inhibit the proliferation of HER2-expressing cancer cells. Further efforts to augment the biologic specificity and efficacy and to develop new technologies for the purification of the peptide from the E coli system are needed.

The Usefulness of Ultrasound-Guided Core Needle Biopsy for Non-Palpable Breast Lesion

PURPOSE: To determine the usefulness of ultrasound-guided core biopsy for the diagnosis of non-palpable beast lesions. MATERIALS AND METHODS: Between April 1996 and December 2000, 932 lesions in 901 patients were the object of ultrasound-guided core biopsy. Of these, 440 non-palpable lesions ranging in size from 0.3 to 3.0 (average, 0.9)cm, and found in 428 patients (all women aged, on average, 43.9 years), were included in this study. The pathologic results of core biopsy were compared with the available surgical data, and clinical and radiologic follow-up data were also reviewed. A 16-gauge needle was used in 197 lesions, and a 14-gauge neadle in the other 243. RESULTS: At core biopsy, 53 lesions were diagnosed as invasive carcinoma, and 45 of these were excised. Forthfour were confirmed as invasive carcinoma, and in one case there was no residual tumor. Seven lesions, diagnosed as ductal carcinoma in situ at core biopsy, were surgically removed, and the final diagnosis was ductal carcinoma in four cases and invasive carcinoma in two. Two of four cases initially diagnosed as atypical ductal hyperplasia were finally diagnosed as invasive carcinoma after surgery. Six lesions diagnosed at core biopsy asbenign were later found to be malignant (false-negative rate, 8.3%). Radiologic imaging suggested that all six lesions-for two of which, a 14-gauge needle was used, and for four, a 16-gauge needle-were malignant. The false-negative rate was 5.1% and 12%, respectively, whithout statistical significance (p=0.26). CONCLUSION: Ultrasound-guided core needle biopsy for non-palpable breast lesions is useful and can replace surgical excision. To avoid false-negative assessment, however, strict radiologic-histopathologic correlation is required.

The Role of Sonography in Patients with Breast Cancer Presenting as an Axillary Mass

OBJECTIVE: To compare sonography and mammography in terms of their diagnostic value in breast cancer cases which initially presented as an axillary mass without a palpable mass or other clinical symptoms. MATERIALS AND METHODS: Seven patients with enlarged axillary lymph nodes who first presented with no evidence of palpable breast lesions and who underwent both mammography and sonography were enrolled in this study. In six of the seven, the presence of metastatic adenocarcinoma was confirmed preoperatively by axillary needle aspiration biopsy; in four, subsequent sonographicallyguided breast core biopsy performed after careful examination of the primary site indicated that primary breast cancer was present. In each case, the radiologic findings were evaluated by both breast sonography and mammography. RESULTS: Breast lesions were detected mammographically in four of seven cases (57%); in three of the four, the lesion presented as a mass, and in one as microcalcification. In three of these four detected cases, fatty or scattered fibroglandular breast parenchyma was present; in one, the parenchyma was dense. In the three cases in which lesions were not detected, mammography revealed the presence of heterogeneously dense parenchyma. Breast sonography showed that lesions were present in six of seven cases (86%); in the remaining patient, malignant microcalcification was detected at mammography. Final pathologic examination indicated that all breast lesions except one, which was a ductal carcinoma in situ, with microinvasion, were infiltrating ductal carcinomas whose size ranged from microscopic to greater than 3 cm. At the time of this study, all seven patients were alive and well, having been disease free for up to 61 months after surgery. CONCLUSION: In women with a palpable axillary mass confirmed as metastatic adenocarcinoma, breast sonography may be a valuable adjunct to mammography.

Neoadjuvant Chemotherapy for the Local Advanced Breast Cancer / 한국유방암학회지

PURPOSE: The definition of locally advanced breast cancer (LABC) includes stage III breast cancer. In order to investigate the factors influencing on the final outcome we analysed the data of LABC patients that received neoadjuvant chemotherapy prior to definitive surgery. METHODS: 122 LABC patients, who underwent neoadjuvant chemotherapy between 1980 and 1997, were included for the analysis. Clinical responses to neoadjuvant chemother apy were classified as complete response (CR), partial response (PR), and no response (NR). Overall survival (OS), Loco-regional relapse free survival (LRRFS), and distant relapse free survival (DRRFS) probabilities were investigated according to initial clinical stage, clinical response to neoadjuvant chemotherapy, and pathologic stage after neo adjuvant chemotherapy. Statistical analyses were performed with chi2-test, Kaplan-Meier, and Cox-regression methods using SPSS. RESULTS: The mean age at diagnosis was 47 years old (range 31~73) and median follow-up period was 61.6 months (range 3~227 months). Among 122 LABC patients, 69 (56.6%) were included in stage IIIA, 37 (30.3%) in stage IIIB, and 16 (13.1%) in IIIC at diagnosis. 10 patients (8.2%) have shown CR, 85 (69.7%) patients PR, and the remaining 27 (22.1%) patients showed NR. The overall response rate to neoadjuvant chemotherapy was 77.5%. However, only 51 (41.8%) were demonstrated to have pathologically down-staged results. There were 32 loco-regional recurrences and 59 distant metastases. All of the initial clinical stage, clinical response to neoadjuvant chemotherapy, and pathologic stage influenced the final outcome of 10 year OS, LRRFS, DRFS. However, in multivariate analysis pathologic stage after neoadjuvant chemotherapy was the most influencing factor on the final outcome. CONCLUSION: Pathologic stage after neoadjuvant chemotherapy could be the most important prognostic factor of the LABC.

Ductal Carcinoma in Situ (DCIS) and Ductal Carcinoma in Situ with Microinvasion (DCIS-MI) of the Breast

PURPOSE: The use of mammographic screening has led to the early detection of breast cancers as well as the increasing incidence of ductal carcinoma in situ (DCIS) and DCIS with microinvasion (MI). The biologic behaviors and management of DCIS and DCIS with MI remain uncertain and controversial. We designed this study to investigate the differences in clinical behavior and association with pathological parameter of both DCIS and DCIS with MI. METHODS: DCIS with MI was defined as DCIS with and invasive area of 1 mm or less in greatest dimension. We analyzed and compared the clinico-pathological features and treatment outcomes of 155 DCIS patients and 73 DCIS with MI patients. Chi-square test, student t-test and Kaplan-Meier method using SPSS 9.0 for MS-windows were used to verify the statistical significance. RESULTS: Both DCIS with MI and DCIS were most prevalent in women in the fifth decade, and the mean ages of the two groups were 45.0 and 46.8 years old, respectively. The primary tumors of DCIS with MI were more palpable (72.6% vs. 56.8%, P=0.032) upon physical examination and larger (3.1+/-0.21 cm vs. 2.6+/-0.12 cm, P=0.037) than those of the DCIS group. The rate of axillary lymph node metastasis was higher in the DCIS with MI group (8.3% vs. 0.7%, P=0.003). The DCIS with MI group was more commonly associated with high nuclear grade (50% vs. 28%, P=0.028). The DCIS with MI group was also linked with comedo type, although not to a statistically significant degree (67.6% vs. 52.6%, P=0.095). In terms of hormone receptor, there was no significant difference between the groups. There were three systemic metastases in DCIS patients and two DCIS with MI patients (P>0.05). There were no local-regional recurrences in either groups. The 8-year disease-free survival rates of the DCIS and DCIS with MI groups were 98.1% and 95.8% respectively (P>0.05). CONCLUSION: DCIS with MI has several clinical-pathological characterisitcs: more palpable on physical examination, larger in size, higher incidence of lesions with comedo necrosis and high nuclear grade. Examination of the axillary lymph node with less invasive techniques may be necessary in cases with suspicious invasion. Since DCIS with MI is thought to be a transitional disease entity between DCIS and invasive ductal carcinoma and has a metastatic potential, a careful histologic evaluation is necessary for the diagnosis of DCIS.

Risk Factors of Local Recurrence in Phyllodes Tumor

PURPOSE: A phyllodes tumor is a rare disease of the breast, which shows various clinicopathological aspects. However, there is some controversy over its clinical behavior, pathologic characteristics, and local recurrence rates. Therefore, the clinicopathological characteristics of phyllodes tumor and the risk factor that influence a local recurrence after surgery were analyzed. METHODS: The medical records of 56 patients with a phyllodes tumor who had undergone surgery at the Department of Surgery, Yonsei University, from 1986 to 1998, were analyzed retrospectively. The median follow up period was 57.2 months (12~245 months). The microscopic slides were re-examined and the pathologic criteria analyzed were cellular atypia, stromal cellularity, pleomorphism, necrosis, differentiation, tumor margin, and number of mitoses. The malignancy was reclassified using the histological criteria reported by Pietruszka et al. (benign was 0~4 mitoses/10 high- power fields, borderline 5~9 mitoses, and malignant more than 10 mitoses). The clinical features evaluated included age, preoperative diagnosis, tumor size, surgical methods, and local recurrence. RESULTS: The mean age was 41 years 14~69 years) and the mean tumor size was 4.5 cm (1~12 cm). Only 9 cases (16.1%) were preoperatively diagnosed as having a phyllodes tumor. The most commonly performed surgical procedures were local or wide excision (46 cases, 82.1%), and a mastectomy in 10 cases (17.9%). Out of 56 cases reviewed, 43 (76.8%) were confirmed as being a benign, 7 (12.5%) as being a borderline, and 5 (1.8%) as being a malignant phyllodes tumor. Cellular atypia was minimal in 40 cases (71.4%) and prominent in 14 cases (25.0%). The stromal cellularity was minimal in 32 cases (57.1%) and prominent in 23 cases (41.1%). Pleomorphism and necrosis were represented in only 1 case (1.8%). The tumor margin was infiltrating in 11 cases (19.6%) and pushing in 43 cases (76.8%). A local recurrence developed in 9 cases (16.1%). There were no dependable histopathological features to predict a local recurrence except for cellular atypia, stromal cellularity, and an infiltrating tumor margin. CONCLUSION: From the above results, the strong prognostic factors that can be used to predict a local recurrence appear to be cellular atypia, stromal cellularity, and an infiltrating tumor margin.

Body Mass Index as a Risk and Prognostic Factor of Breast Cancer

PURPOSE: In order to study the effect of body mass index (BMI) on the risk and the prognosis of breast cancers, we analyzed the BMI and clinico-pathological data of the breast cancer patients. We compared the BMIs of breast cancer patients to those of normal women and investigated the association of the BMI with the clinico-pathological data. Then the overall and disease-free survial probabilities were analyzed according to the BMI groups. METHODS: 1,201 breast cancer patients were available for the analysis of BMI and the BMI of the normal control women was adopted from the report of the National Health, Nutrition Survey of 1998. We classified the BMI groups by he World Health Organization classification as follows; BMI under 18.5 as under-weight group, 18.5-24.9 as the normal weight group, 25-30 as the overweight group, and over 30 as the obesity group. BMI was compared between the patient group and the control group by age, while the correlation between BMI and the clinico-pathological characteristics and the recurrence and survival rates for each BMI group were comparatively analyzed. The statistical analysis were performed using x2 test, one-way ANOVA, independent T-test, and one sample T test, and the survival probabilities were generated by Kaplan-Meier methods. RESULTS: The means of BMI increased by aging in both the patients and the control group. The means of BMI of the 30s and 50s were significantly lower in breast cancer patients than those of normal women (P=0.001, 0.002). However, those of 60s and 70s were higher in breast cancer patients with marginal significance (P=0.159). In the pre- menopausal patient group, BMI was associated with the tumor size (P=0.012) and the tumor stage (P=0.018). In the post-menopausal patients, on the other hand, BMI had positive relationship with well-differentiation of the tumor (P=0.025), and also showed a marginal association with estrogen receptor positivity (P=0.074). BMI did not influence on the outcome of premenopausal breast cancer patients but lower BMI (underweight group) showed poorer outcome in postmenopausal patients in terms of overall survival (P= 0.278), locoregional relapse-free survival (P=0.581), and distant relapse-free survival (P=0.040). CONCLUSIONS: As a breast cancer risk factor, BMI seems to have a different association by the age. Higher BMI for the 60s and 70s but lower BMI for the younger age group seems to be a risk factor for the breast cancer development. In terms of the relationship with the clinico-pathological characteristics, BMI has different association by the menopausal status. BMI did not influence on the outcome of premenopausal breast cancer patients but lower BMI (underweight group) showed significantly poorer outcome in postmenopausal patients.