This article was initially published on the Journal of Breast Cancer with a misspelled the Institutional Review Board (IRB) approval number. The IRB number should be corrected as “NCC2014-0031”.

Ectopic breast tissue and male breast cancer are both very rare diseases with only a few reports in the literature. Here, we present the first case of ectopic male breast cancer in the perineum. The patient was a 70-year-old man with a palpable mass in the perineum. A wide local excision and inguinal lymph node dissection revealed invasive breast carcinoma of no special type involving the skin and subcutis, and inguinal lymph node metastases. Immunohistochemical staining showed that the tumor cells were strongly positive for estrogen and progesterone receptors and negative for human epidermal growth factor receptor 2. Moreover, no p53 overexpression was observed. Herein, the clinical and pathologic features, as well as a review of ectopic male breast cancer are discussed.
Aged ; Breast ; Breast Neoplasms ; Breast Neoplasms, Male* ; Estrogens ; Humans ; Lymph Node Excision ; Lymph Nodes ; Male ; Male* ; Mammary Glands, Human ; Neoplasm Metastasis ; Perineum* ; Rare Diseases ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Skin

Two consecutive surveys for breast surgeons in Korea were conducted to comprehend the practice patterns and perceptions on margin status after breast-conserving surgery. The surveys were conducted online in 2014 (initial) and 2016 (follow-up). A total of 126 and 88 responses were obtained in the initial and follow-up survey, respectively. More than 80% of the respondents replied to routinely apply frozen section biopsy for intraoperative margin assessment in both surveys. Re-excision recommendations of the margin for invasive cancer significantly changed from a close margin to a positive margin over time (p=0.033). Most of the respondents (73.8%) defined a negative margin as “no ink on tumor” in invasive cancer, whereas more diverse responses were observed in ductal carcinoma in situ cases. The influence of guideline establishment for negative margins has been identified. A high uptake rate of intraoperative frozen section biopsy was noted and routine use needs reconsideration.
Biopsy ; Breast ; Carcinoma, Intraductal, Noninfiltrating ; Follow-Up Studies ; Frozen Sections ; Ink ; Korea ; Mastectomy, Segmental* ; Surgeons* ; Surveys and Questionnaires

PURPOSE: Breast cancer has a high prevalence in Korea. To achieve personalized therapy for breast cancer, long-term follow-up specimens are needed for next-generation sequencing (NGS) and multigene analysis. Formalin-fixed paraffin-embedded (FFPE) samples are easier to store than fresh frozen (FF) samples. The objective of this study was to optimize RNA extraction from FFPE blocks for NGS. METHODS: RNA quality from FF and FFPE tissues (n=5), expected RNA amount per unit area, the relationship between archiving time and quantity/quality of FFPE-extracted RNA (n=14), differences in quantitative real-time polymerase chain reaction (qRT-PCR) and NGS results, and comparisons of both techniques with tissue processing at different institutions (n=96) were determined in this study. RESULTS: The quality of RNA did not show any statistically significant difference between paired FF and FFPE specimens (p=0.49). Analysis of tumor cellularity gave an expected RNA amount of 33.25 ng/mm2. Archiving time affected RNA quality, showing a negative correlation with RNA integrity number and a positive correlation with threshold cycle. However, RNA from samples as old as 10 years showed a 100% success rate in qRT-PCR using short primers, showing that the effect of archiving time can be overcome by proper experiment design. NGS showed a higher success rate than qRT-PCR. Specimens from institution B (n=46), which were often stored in a refrigerator for more than 6 hours and fixed without slicing, showed lower success rates and worse results than specimens from the other institutes. CONCLUSION: Archived FFPE tissues can be used to extract RNA for NGS if they are properly processed before fixation. The expected amount of RNA per unit size calculated in this study will be useful for other researchers.
Academies and Institutes ; Breast Neoplasms ; Estrogens ; Follow-Up Studies ; Humans ; Korea ; Prevalence ; Real-Time Polymerase Chain Reaction ; RNA* ; Sequence Analysis

PURPOSE: The aims of our study were to correlate the degree of metabolic activity in normal glandular tissue measured on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) with qualitative background parenchymal enhancement (BPE) grades on magnetic resonance imaging (MRI), and to investigate the change in standardized uptake value (SUV) according to the patients' menstrual cycles. METHODS: From January 2013 to December 2015, 298 consecutive premenopausal patients with breast cancer who underwent both breast MRI and 18F-FDG PET/CT were identified. BPE was evaluated in the contralateral breast of cancer patients and categorized as minimal, mild, moderate, or marked based on Breast Imaging Reporting and Data System criteria. We analyzed the correlation between BPE and maximum SUV (SUVmax) and mean SUV (SUVmean) values. We also analyzed the metabolic activity of normal glandular tissue according to the patients' menstrual cycles. RESULTS: The mean SUVmax and SUVmean values differed significantly according to BPE grade (p < 0001), with the lowest values occurring in the minimal group and the highest values occurring in the marked group. Spearman's correlation coefficients revealed moderate correlations between BPE grade and SUVmax (r=0.472, p < 0.001) and BPE and SUVmean (r=0.498, p < 0.001). The mean SUVmax and SUVmean values differed significantly according to the patients' menstrual cycles, with the highest values in the 3rd week and the lowest value in the 2nd week. Of 29 patients with low metabolic parenchyma (high BPE but low SUVmean values), 17 (58.6%) were in the 4th week of their menstrual cycle. CONCLUSION: The metabolic activity of normal breast parenchyma, which is highest in the 3rd week and lowest in the 2nd week of the menstrual cycle, correlates moderately with BPE on MRI. Metabolic activity tends to be lower than blood flow and vessel permeability in the 4th week of the menstrual cycle.
Breast ; Breast Neoplasms ; Electrons* ; Female ; Fluorodeoxyglucose F18 ; Humans ; Information Systems ; Magnetic Resonance Imaging ; Menstrual Cycle* ; Metabolism ; Permeability ; Positron-Emission Tomography and Computed Tomography

PURPOSE: Pathological complete response (pCR) of axillary lymph node (LN) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC). Treatment of the axilla after NAC is not well established and the value of sentinel LN biopsy following NAC remains unclear. This study investigated the predictive value of axillary response following NAC and evaluated the predictive value of a model based on axillary response. METHODS: Data prospectively collected on 201 patients with clinically node-positive breast cancer who were treated with NAC and underwent axillary LN dissection (ALND) were retrieved. A model predictive of axillary pCR was developed based on clinicopathologic variables. The overall predictive ability between models was compared by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 201 patients who underwent ALND after NAC, 68 (33.8%) achieved axillary pCR. Multivariate analysis using axillary LN pCR after NAC as the dependent variable showed that higher histologic grade (p=0.031; odds ratio [OR], 2.537; 95% confidence interval [CI], 1.087–5.925) and tumor response rate ≥47.1% (p=0.001; OR, 3.212; 95% CI, 1.584–6.515) were significantly associated with an increased probability of achieving axillary pCR. The area under the ROC curve for estimating axillary pCR was significantly higher in the model that included tumor response rate than in the model that excluded this rate (0.732 vs. 0.649, p=0.022). CONCLUSION: Tumor response rate was the most significant independent predictor of axillary pCR in response to NAC. The model that included tumor response rate was a significantly better predictor of axillary pCR than the model that excluded tumor response rate.
Axilla ; Biopsy ; Breast Neoplasms* ; Breast* ; Drug Therapy* ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neoadjuvant Therapy ; Odds Ratio ; Polymerase Chain Reaction ; Prospective Studies ; ROC Curve

PURPOSE: Currently, there is little information regarding optimal treatment for metastatic breast cancer (MBC) in elderly patients. In this retrospective study, we examined a cohort of elderly patients with MBC receiving a range of treatments, in terms of demographic and clinicopathologic characteristics, treatment patterns, and outcomes. METHODS: Patients aged 65 years and older, and diagnosed with MBC between 2003 and 2015, were identified from the databases of three academic hospitals in South Korea. A total of 161 cases were eligible for inclusion. We assessed clinicopathologic features, treatment patterns, and outcomes, using the available electronic medical records. Based on age at MBC diagnosis, patients were divided into three groups: 65 to 69, 70 to 74, and ≥75 years. RESULTS: Most patients had received active treatment according to biologic subtype as in younger patients, although frequent dose modifications were observed during chemotherapy. The median overall survival (OS) for all patients was 30.3 months; age (≥70 years), Eastern Cooperative Oncology Group (ECOG) performance status (PS) (≥2), triple-negative cancer, and number of metastatic sites (≥2) were significant poor prognostic factors for OS in multivariate analyses. All types of systemic treatments according to biologic subtype conferred more prolonged OS in patients receiving treatment. Patients aged ≥75 years were more likely to have a poor ECOG PS and advanced comorbidity, and tended to receive less intensive treatments compared to the other age groups. CONCLUSION: Elderly patients with MBC should not be excluded from receiving standard treatments prescribed for younger patients. Future research plans for elderly patients, especially aged ≥75 years with breast cancer, should include a geriatric assessment for identifying individuals at risk for treatment-related toxicity. Overall, this analysis will provide a better understanding of this population and help guide clinical care in real-world practice.
Aged* ; Breast Neoplasms* ; Breast* ; Cohort Studies ; Comorbidity ; Diagnosis ; Drug Therapy ; Electronic Health Records ; Geriatric Assessment ; Humans ; Korea ; Multivariate Analysis ; Retrospective Studies*

PURPOSE: Wnt7a is a glycoprotein involved in embryonic development and the progression of different types of malignant tumors. This study aimed to detect the level of Wnt7a expression in breast cancer and explore its role in the disease progression and prognosis. METHODS: A total of 258 patients diagnosed with invasive ductal carcinoma of the breast were included in this study. Using tissue microarray and immunohistochemical staining, we evaluated the association between Wnt7a expression and clinicopathological parameters, and the prognostic value of Wnt7a. RESULTS: Wnt7a expression was significantly correlated with estrogen receptor (ER) expression (odds ratio, 3.95; 95% confidence interval [CI], 1.99–7.80; p < 0.001). On univariate and multivariate analyses, loss of Wnt7a expression was associated with poor disease-free survival (DFS) (multivariate hazard ratio [HR], 9.12; 95% CI, 1.80–46.09; p=0.008), but not with poor overall survival (OS). In the ER-positive group (n=114), loss of Wnt7a expression was an independent prognostic factor for shorter DFS (multivariate HR, 13.54; 95% CI, 1.11–165.73; p=0.042) and OS (multivariate HR, 4.76; 95% CI, 1.29–17.61; p=0.019) on univariate and multivariate analyses. However, in the ER-negative group, there was no significant difference in DFS and OS according to Wnt7a expression. CONCLUSION: The loss of Wnt7a expression might be a meaningful factor in assessing DFS and OS, especially in ER-positive breast cancer.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Disease Progression ; Disease-Free Survival ; Embryonic Development ; Estrogens* ; Female ; Glycoproteins ; Humans ; Multivariate Analysis ; Pregnancy ; Prognosis ; Receptors, Estrogen ; Wnt Proteins

PURPOSE: Whether tamoxifen affects the risk of neurodegenerative disease is controversial. This nationwide population-based study investigated the risk of Parkinson's disease (PD) associated with tamoxifen treatment in female patients with breast cancer using Taiwan's National Health Insurance Research Database. METHODS: A total of 5,185 and 5,592 female patients with breast cancer who did and did not, respectively, receive tamoxifen treatment between 2000 and 2009 were included in the study. Patients who subsequently developed PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the aforementioned groups. RESULTS: Tamoxifen did not significantly increase the crude rate of developing PD in female patients with breast cancer (tamoxifen group, 16/5,169; non-tamoxifen group, 11/5,581; p=0.246). Tamoxifen did not significantly increase the adjusted hazard ratio (aHR) for subsequently developing PD (aHR, 1.310; 95% confidence interval [CI], 0.605–2.837; p=0.494). However, tamoxifen significantly increased the risk of PD among patients followed up for more than 6 years (aHR, 2.435; 95% CI, 1.008–5.882; p=0.048). CONCLUSION: Tamoxifen treatment may increase the risk of PD in Taiwanese female patients with breast cancer more than 6 years after the initiation of treatment.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; Female* ; Humans ; National Health Programs ; Neurodegenerative Diseases ; Parkinson Disease* ; Proportional Hazards Models ; Tamoxifen*

PURPOSE: This study aimed to evaluate the efficacy and safety of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy beyond standard treatment for anthracycline- and taxane-pretreated metastatic breast cancer (MBC). METHODS: We consecutively enrolled 158 MBC patients who underwent CMF chemotherapy in a palliative setting at two academic hospitals in Korea between 2002 and 2016. RESULTS: The median age of the 158 enrolled patients was 51 years (range, 30–77 years). The enrolled patients were treated with a median of 5 lines of systemic treatment (range, 2–11) before CMF therapy, and the median time from diagnosis of MBC to CMF administration was 36.0 months (range, 7.1–146.7 months). The median number of cycles of CMF treatment was 3 (range, 1–19), and the relative dose intensity was 90.4%. The toxicity profile was mild, with an observed 3.1% of grade 2 and 5.0% of grade 3/4 neutropenia. Among 147 patients (93.0%) whose response to CMF was evaluated, the response rate was 10.9% (16/147), with complete response (CR) in one and partial response (PR) in 15. In addition, the disease control rate (calculated as CR+PR+stable disease) was 44.2% (65/147). The median progression-free survival and overall survival were 3.1 months (95% confidence interval [CI], 2.7–3.6) and 9.4 months (95% CI, 7.1–11.6), respectively. CONCLUSION: CMF therapy is effective and tolerable as salvage treatment for heavily pretreated MBC.
Breast Neoplasms* ; Breast* ; Cyclophosphamide* ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Fluorouracil* ; Humans ; Korea ; Methotrexate* ; Neutropenia ; Palliative Care* ; Retrospective Studies* ; Salvage Therapy