PURPOSE: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. METHODS: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled. The core needle biopsy specimens acquired before NAC were used to analyze the clinicopathologic variables and overall performance of the predictive model for therapeutic response. RESULTS: Independent predictors of pathologic complete response after NAC were found to be higher number of tumor infiltrating lymphocytes (p=0.007), absence of clear cytoplasm (p=0.008), low necrosis (p=0.018), and high histologic grade (p=0.039). In the receiver operating characteristics curve analysis, the area under curve for the combination of these four variables was 0.777. CONCLUSION: The present study demonstrated that a predictive model using the above four variables can predict therapeutic response to single-regimen NAC with the combination of doxorubicin, cyclophosphamide, and docetaxel in TNBC. Therefore, adding these morphologic variables to clinical and genomic signatures might enhance the ability to predict the therapeutic response to NAC in TNBC.
Area Under Curve ; Biopsy, Large-Core Needle ; Chemotherapy, Adjuvant ; Cyclophosphamide ; Cytoplasm ; Doxorubicin ; Drug Therapy* ; Humans ; Lymphocytes, Tumor-Infiltrating ; Necrosis ; Neoadjuvant Therapy ; ROC Curve ; Treatment Outcome ; Triple Negative Breast Neoplasms*

Mammary carcinoma arising in microglandular adenosis (MGA) is extremely rare, and MGA is regarded as a non-obligate precursor of triple-negative breast cancer. We report five cases of carcinoma arising in MGA of the breast. All cases showed a spectrum of proliferative lesions ranging from MGA to atypical MGA, ductal carcinoma in situ or invasive carcinoma. Immunohistochemically, all cases were triple-negative and expression of S-100 protein gradually decreased as the lesions progressed from MGA to atypical MGA and carcinoma. Three cases showed acinic cell differentiation with reactivity to α1-antitrypsin, and one case was metaplastic carcinoma. During clinical follow-up, one patient developed local recurrence. Carcinoma arising in MGA is a rare but distinct subset of triple-negative breast cancer with characteristic histologic and immunohistochemical findings.
Acinar Cells ; Breast ; Carcinoma, Intraductal, Noninfiltrating ; Fibrocystic Breast Disease* ; Follow-Up Studies ; Humans ; Recurrence ; S100 Proteins ; Triple Negative Breast Neoplasms

PURPOSE: The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-α, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, N-cadherin, and E-cadherin) was evaluated using immunohistochemistry. RESULTS: High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR-222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. CONCLUSION: This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer.
Actins ; Breast Neoplasms* ; Breast* ; Cadherins ; Down-Regulation ; Epithelial-Mesenchymal Transition ; Estrogens ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; Multigene Family ; Muscle, Smooth ; Osteonectin ; Phenobarbital ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; Tamoxifen

BACKGROUND: As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. METHODS: Thirty observers from thirty different institutions reviewed Ki-67-stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. RESULTS: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. CONCLUSIONS: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.
Breast Neoplasms* ; Breast* ; Observer Variation* ; Online Systems

BACKGROUND: This study was performed to analyze cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and its impact on the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). METHODS: Five thousand five hundred and forty-nine cases of thyroid fine-needle aspiration cytology (FNAC) diagnosed between 2012 and 2014 were included in this study. Diagnostic categories based on TBSRTC were compared with final surgical diagnoses, and the ROM in each category was calculated both when NIFTP was included in malignant lesions and when excluded from malignant lesions. RESULTS: Of the 5,549 thyroid FNAC cases, 1,891 cases underwent surgical resection. In final diagnosis, 1,700 cases were revealed as papillary thyroid carcinoma (PTC), and 25 cases were reclassified as NIFTP. The cytologic diagnoses of NIFTP were non-diagnostic in one, benign in five, atypia of undetermined significance (AUS) in 14, follicular neoplasm in two, and suspicious for malignancy in three cases. Collectively, NIFTP/encapsulated follicular variant of PTC (EFVPTC) were more frequently classified as benign, AUS, or follicular neoplasm and less frequently categorized as malignant compared to conventional PTCs. Exclusion of NIFTP from malignant diagnoses resulted in a slight decrease in malignancy rates in non-diagnostic, benign, AUS, follicular neoplasm, and suspicious for malignancy categories without any statistical significance. CONCLUSIONS: The decrease in the ROM was not significant when NIFTP was excluded from malignant lesions. In thyroid FNACs, NIFTP/EFVPTCs were mostly classified into indeterminate categories. Therefore, it might be feasible to separate NIFTP/EFVPTC from conventional PTC on FNAC to guide clinicians to conservative management for patients with NIFTP/EFVPTC.
Biopsy, Fine-Needle ; Diagnosis ; Humans ; Thyroid Gland ; Thyroid Neoplasms

PURPOSE: There is cumulative evidence that changes in biomarker status occur frequently during the metastatic progression of breast cancer and affect treatment response. The purpose of this study was to evaluate the frequency of biomarker changes in metastatic breast cancer (MBC) and its impact on prognosis. METHODS: A total of 152 patients diagnosed with MBC at the time of initial diagnosis or during post-surgical follow-up were included. Changes in biomarker status in MBCs, their frequency according to various metastatic sites, tumor characteristics, and their association with patient survival were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status changed in 9 (6.0%), 40 (26.3%), 12 (7.9%), and 29 (19.1%) patients, respectively. ER, PR, and HER2 mainly showed positive to negative conversion, whereas Ki-67 changed mostly from a low to high index. There were no differences in the frequencies of biomarker changes according to the metastatic sites. As for ER and HER2, cases with negative conversion showed low expression levels in the primary tumor. Survival analyses indicated that a positive to negative conversion of ER was an independent poor prognostic factor in patients with primary ER-positive breast cancer. CONCLUSION: Changes in biomarker status are not rare, and usually occur in an unfavorable direction in breast cancer metastases. Negative conversion of ER status is a predictor of poor prognosis. Thus, it is beneficial to evaluate changes in biomarker status in MBC not only for the purpose of determining treatment options but also for prognostication of patients.
Biomarkers ; Breast Neoplasms ; Breast ; Diagnosis ; Estrogens ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone

PURPOSE: The management of benign intraductal papilloma (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial. This study was performed to evaluate the rate of upgrading to malignancy or high-risk lesions after excision and to identify factors associated with upgrading using a large series of benign IDP cases without atypia. METHODS: We included patients who were diagnosed as having benign IDP without atypia on CNB and underwent surgical or vacuum-assisted excision between 2010 and 2015. We analyzed the clinical, radiologic, and histopathologic features of IDPs that were upgraded to malignancy or high-risk lesions after excision. RESULTS: A total of 511 benign IDPs without atypia diagnosed via CNB were identified, of which 398 cases were treated with excision. After reviewing these cases, four cases of high-risk lesions in adjacent tissue on CNB, two cases which were revealed as papilloma with atypia, and nine cases of malignancy in the same breast were excluded. In the remaining 383 cases, the rate of upgrading to malignancy and high-risk lesions after excision was 0.8% and 4.4%, respectively. The presence of concurrent contralateral breast cancer, the presence of symptoms, and multifocality were factors significantly associated with upgrading to malignancy on subsequent excision. Surgical excision rather than vacuum-assisted excision was significantly associated with upgrading to high-risk lesions or malignancy. CONCLUSION: The rate of upgrading to malignancy for benign IDP without atypia was very low, suggesting that close clinical and radiologic observation may be sufficient for patients with benign IDP without atypia on CNB under proper settings.
Biopsy, Large-Core Needle* ; Breast ; Breast Neoplasms ; Humans ; Papilloma ; Papilloma, Intraductal*

Fibrosing mediastinitis is a rare disease that is characterized by the proliferation of dense fibrous tissue of the mediastinum. The pathogenesis of fibrosing mediastinitis is unknown in most cases. However, histoplasmosis, tuberculosis, autoimmune disease, radiation therapy, and other idiopathic fibroinflammatory diseases have been implicated in some cases. Most clinical features are related to an obstruction or compression of the mediastinal structure. Fibrosing mediastinitis is often progressive and occurs diffusely throughout the mediastinum. We encountered a case of fibrosing mediastinitis of a very focal lesion without evidence of mediastinal involvement. The condition was confirmed by biopsy and graft bypass surgery was performed because of SVC syndrome.
Autoimmune Diseases ; Biopsy ; Histoplasmosis ; Mediastinitis* ; Mediastinum ; Rare Diseases ; Transplants ; Tuberculosis

OBJECTIVE: This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab or thrombolytics (urokinase or t-PA) during the procedures. MATERIALS AND METHODS: From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1,180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-SealTM; the suture-mediated closure device was The Closer STM) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n = 94), thrombolytics only (n = 10), heparin and thrombolytics (n = 3), or abciximab and thrombolytics (n = 1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two groups. RESULTS: The immediate hemostasis rates were 92.9% (1,456/1,568) in the no-drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups (p = 0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture-mediated devices was also not statistically significant (92.9% vs. 84.8%, respectively; p = 0.21). CONCLUSION: Arterial closure of the femoral access site with using vascular closure devices is both safe and effective, even in the patients who received heparin, abciximab or thrombolytics.
Sutures ; Prospective Studies ; Postoperative Complications ; Middle Aged ; Male ; Immunoglobulin Fab Fragments/pharmacology/*therapeutic use ; Humans ; Hemostatic Techniques/*instrumentation ; Hemostasis/*drug effects ; Fibrinolytic Agents/pharmacology/*therapeutic use ; Femoral Artery/*surgery ; Female ; Collagen ; Anticoagulants/pharmacology/*therapeutic use ; Antibodies, Monoclonal/pharmacology/*therapeutic use

PURPOSE: Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST. MATERIALS AND METHODS: The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup. CONCLUSION: ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.
Biomarkers ; Biopsy ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Estrogens ; Humans ; Multivariate Analysis ; Neoadjuvant Therapy ; Progesterone* ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone*