Multilevel analysis is an appropriate and powerful tool for analyzing hierarchical structure data widely applied from public health to genomic data. In practice, however, we may lose the information on multiple nesting levels in the multilevel analysis since data may fail to capture all levels of hierarchy, or the top or intermediate levels of hierarchy are ignored in the analysis. In this study, we consider a multilevel linear mixed effect model (LMM) with single imputation that can involve all data hierarchy levels in the presence of missing top or intermediate-level clusters. We evaluate and compare the performance of a multilevel LMM with single imputation with other models ignoring the data hierarchy or missing intermediate-level clusters. To this end, we applied a multilevel LMM with single imputation and other models to hierarchically structured cohort data with some intermediate levels missing and to simulated data with various cluster sizes and missing rates of intermediate-level clusters. A thorough simulation study demonstrated that an LMM with single imputation estimates fixed coefficients and variance components of a multilevel model more accurately than other models ignoring data hierarchy or missing clusters in terms of mean squared error and coverage probability. In particular, when models ignoring data hierarchy or missing clusters were applied, the variance components of random effects were overestimated. We observed similar results from the analysis of hierarchically structured cohort data.

PURPOSE: We evaluated the effect of local recurrence (LR) and regional recurrence (RR) on distant metastasis and survival in patients treated with breast conservation therapy (BCT). METHODS: We analyzed 907 patients who were treated for invasive breast cancer between 1993 and 2006. With 53 months of follow-up, 28 patients (3.1%) developed LR in the breast and 12 patients (1.3%) developed RR before distant metastasis. LR and RR were separated into four patterns to determine the prognostic relevance of recurrence site and time to recurrence: LR within 3 years (early LR), LR after 3 years (late LR), RR within 3 years (early RR), and RR after 3 years (late RR). RESULTS: Early LR (hazard ratio [HR], 4.76; p=0.003) and early RR (HR, 18.16; p<0.001) were independent predictors of distant metastasis. In terms of overall survival, early LR (HR, 5.24; p=0.002), and early RR (HR, 18.80; p<0.001) were significantly related with poor survival. Patients with late LR/RR had a similar favorable prognosis compared with patients who never experienced LR/RR. CONCLUSION: The result suggests that time to LR/RR following BCT is a significant predictor developing a distant metastasis and surviving.
Breast ; Breast Neoplasms ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Prognosis ; Recurrence

PURPOSE: Breast conservation surgery (BCS) has become a standard treatment method for patients with early breast cancer. Endoscopy-assisted BCS (EABCS) can be performed through an inconspicuous periareolar and a small axillary incision for sentinel node biopsy, which may give better cosmetic outcomes than conventional BCS skin incisions. This study was designed to evaluate the feasibility of EABCS for patients with early breast cancer. METHODS: Forty-three patients were candidates for EABCS, and EABCS was performed in 40 patients with breast cancer between January 2008 and July 2010. Their clinicopathological features were retrospectively analyzed. Operative time, margin status, complications, and relapse-free survival were compared with those of patients treated by conventional BCS and who were treated at the same institute during the same period. RESULTS: The most common lesion site of the EABCS and conventional BCS groups was the upper area of the breast. Tumor size in all patients was less than 4 cm (range, 0.4-3.7 cm), and nodal involvement was found in eight (20%) patients in the BCS group. The mean operative time was 110 minutes for the EABCS group and 107 minutes for the conventional BCS group, and those were not significantly different. No significant difference in frozen or final margin status was observed between the EABCS and conventional BCS groups. Relapse-free survival was statistically equivalent between the groups with a median follow-up of 12 months. Postoperative complications occurred in five cases in four patients with EABCS, which was not significantly different from conventional BCS. CONCLUSION: Performing EABCS in patients with early breast cancer seems to be feasible and safe. Further study with a longer-term follow-up may be needed to confirm the clinical value of EABCS.
Biopsy ; Breast ; Breast Neoplasms ; Cosmetics ; Endoscopy ; Follow-Up Studies ; Humans ; Mastectomy, Segmental ; Nitriles ; Operative Time ; Postoperative Complications ; Pyrethrins ; Retrospective Studies ; Skin ; Survival Rate

PURPOSE: The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. METHODS: A total of 954 patients who had T1–2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. RESULTS: Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. CONCLUSION: Preoperative MRI did not influence survival outcomes in T1–2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1–2 breast cancer may not translate into longer RFS and OS.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Estrogens ; Humans ; Magnetic Resonance Imaging* ; Mastectomy, Segmental ; Multivariate Analysis ; Receptors, Progesterone

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.
Breast ; Breast Neoplasms ; Carcinoma, Papillary ; Disease-Free Survival ; Estrogens ; Humans ; Lymph Nodes ; Mastectomy ; Mastectomy, Segmental ; Prognosis ; Rare Diseases ; Receptors, Progesterone ; Retrospective Studies ; Survival Rate

PURPOSE: Estrogen, various polypeptide hormones and growth factors are associated with the development and progression of breast cancer. Coregulatory proteins are also associated with estrogen receptor (ER) transcriptional activity and tamoxifen resistance. Therefore, it is necessary to investigate the change of coregulator mRNAs and various cell proliferation proteins and cell cycle-related proteins after treatment with estrogen or antiestrogen. METHODS: MCF-7 cells were maintained in dextran-coated charcoal stripped 10% Dulbecco's Modified Eagle Medium (DMEM). To measure the change of the coactivators' (src-1, P/CAF, CBP, AIB1) mRNAs and corepressors' (SMRT, N-coR) mRNAs, multiple PCR was carried out using specific primers. In addition, intracellular proteins related to cell proliferation and cell cycle regulation were measured by performing Western blotting after treatment with estrogen or tamoxifen. The change of mitogen activated protein kinases was also measured by performing Western after tamoxifen treatment for 4 weeks. RESULTS: Coactivator mRNAs expression rapidly decreased in 15 min after estrogen treatment but this recovered to the initial level in 3 hr. The pattern was similar for the case of tamoxifen treatment. Corepressor mRNAs expression rapidly decreased in 15 min after estrogen treatment and it remained at a lower level until 24 hr after estrogen treatment. With tamoxifen treatment, the initial response was similar to the cases of estrogen treatment, but the xpression gradually increased 3 hr after tamoxifen treatment. Treatment of estrogen induced intracellular concentrations of c-myc and Ki-67 and it increased nuclear translocation of NF-kappaB and phosphor-ERK and it decreased the intracellular cell cycle suppressor p27/kip1. Tamoxifen treatment increased nuclear p27/kip1 but it decreased c-myc, NF-kappaB and phosphor-ERK. Long-term (4 weeks) treatment of tamoxifen was associated with decrease of activated ERK and p38 but there was no change in phospho-Akt level. CONCLUSION: Estrogen induced cell proliferation and the survival pathway-related factors, but it decreased the cell cycle suppressor p27/kip1. Long-term treatment with antiestrogen tamoxifen might decrease the MAPK activities in ERalpha-expressing tumor cells.
Blotting, Western ; Breast ; Breast Neoplasms ; Cell Cycle ; Cell Line ; Cell Proliferation ; Charcoal ; Eagles ; Estrogen Receptor Modulators ; Estrogens ; Intercellular Signaling Peptides and Proteins ; MCF-7 Cells ; Mitogen-Activated Protein Kinases ; NF-kappa B ; Peptide Hormones ; Phosphotransferases ; Polymerase Chain Reaction ; Proteins ; RNA, Messenger ; Tamoxifen

PURPOSE: The optimum local surgical strategy regarding breast-conserving therapy (BCT) for triple-negative breast cancer (TNBC) is controversial. To investigate whether BCT is appropriate for patients with TNBC, we evaluated the clinical outcomes of BCT in women with TNBC compared to those of women without TNBC, using a large, single-center cohort. MATERIALS AND METHODS: We performed a retrospective analysis of 1533 women (TNBC n=321; non-TNBC n=1212) who underwent BCT for primary breast cancer between 2000 and 2010. Clinicopathological characteristics, locoregional recurrence-free survival (LRFS), and overall survival (OS) were analyzed. RESULTS: Tumors from the TNBC group had a higher T stage (T2 37.4% vs. 21.0%, p<0.001), a lower N stage (N0 86.9% vs. 75.5%, p<0.001), and a higher histologic grade (Grade III 66.8% vs. 15.4%, p<0.001) than the non-TNBC group. There were no differences in 5-year LRFS rates between the TNBC and non-TNBC groups (98.7% vs. 97.8%, p=0.63). The non-TNBC group showed a slightly better 5-year OS than the TNBC group; however, the difference was not significant (96.2% vs. 97.3%, p=0.72). In multivariate analyses, TNBC was not associated with poor clinical outcomes in terms of LRFS and OS [hazard ratio (HR) for LRFS=0.37, 95% confidence interval (CI): 0.10-1.31; HR for OS=1.03, 95% CI: 0.31-3.39]. CONCLUSION: TNBC patients who underwent BCT showed non-inferior locoregional recurrence compared to non-TNBC patients with BCT. Thus, BCT is an acceptable surgical approach in patients with TNBC.
Adult ; Aged ; Breast Neoplasms/mortality/pathology/*surgery ; Disease-Free Survival ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; *Neoplasm Recurrence, Local/mortality/pathology ; Proportional Hazards Models ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/mortality/pathology/*surgery

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.
Adult ; Aged ; Breast Neoplasms/mortality/pathology/therapy ; Breast Neoplasms, Male/mortality/*pathology/therapy ; Carcinoma, Ductal, Breast/mortality/pathology/therapy ; Disease-Free Survival ; Female ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Young Adult

PURPOSE: During a sentinel lymph node biopsy (SLNB) for breast cancer, the appropriate number of sentinel lymph nodes (SLNs) to be removed for accurate axillary staging is still controversial. We hypothesized that there might be an optimal threshold number of SLNs. We investigated how many SLNs should be removed to achieve an acceptable accuracy and ensure minimal morbidity. METHODS: We reviewed data of 328 patients with invasive breast cancer who underwent SLNB followed by complete level I and II axillary dissection between January 2004 and December 2005. The false negative rate (FNR) and accuracy of SLNB according to the number of removed SLNs were evaluated. RESULTS: The mean number of SLNs removed was 3.0 (range, 1-14), and that of total retrieved axillary lymph nodes was 17.5 (range, 10-40). In total, 111 (33.8%) patients had positive nodes on the permanent pathological report. Among them, 12 patients had negative SLNs; thus, the overall FNR of SLNB was 10.8% (12/111) and the accuracy was 96.3% (316/328). The FNR was 26.6% for a single SLN, 8.0% for two, and 11.1% for three. In cases where four or more SLNs were removed, the FNR decreased to 0% and accuracy reached 100%. CONCLUSION: Our data suggest that a SLNB should not only remove one or two of the hottest node(s) when other hot nodes exist. We also suggest that four might be an optimal threshold number of SLNs to be removed and that removal of more than four SLNs does not improve axillary staging accuracy.
Breast ; Breast Neoplasms ; Dietary Sucrose ; Humans ; Lymph Nodes ; Nitriles ; Pyrethrins ; Sentinel Lymph Node Biopsy

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.
Apoptosis ; Breast ; Breast Neoplasms ; Chemotherapy, Adjuvant ; Cytoplasm ; Estrogens ; Humans ; Multivariate Analysis ; Receptors, Progesterone