Immunohistochemical Survey of Invasive Ductal Carcinoma of the Breast, using ER, PR, HER2 and KI-67 biomarkers, in Uyo, Nigeria

Background: Breast's Invasive Ductal Carcinoma (IDC), which is the commonest type of malignancy in females worldwide, can be characterized using immunohistochemistry in view of personalized cancer therapy. In this study, we aimed to determine the pattern of immunohistochemical profiles of IDC using oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 receptor (HER2) and proliferative index (Ki-67) biomarkers in our tertiary healthcare facility in Uyo, Akwa Ibom State, Nigeria given the dearth of its data in our environment. Materials and methods: We carried out a retrospective hospital-based immunohistochemical study of archival IDC tissue blocks over a four- and half-year period. Using systematic random sampling method, 64 formalin fixed paraffin embedded (FFPE) IDC tissue blocks were selected for this study. We carried out immunohistochemical evaluation using ER, PR, HER2 and Ki-67 biomarkers. Subsequently, we presented the results and classification schemes as text, tables, graphs, and photomicrographs. Results: We found that the proportion of expressions were ER-negative (88.7%), PR-negative (87.3%), HER2-negative (68.3%) and Ki-67 (<20%) being 83.6% respectively. The immunohistochemical-based classification which was done using combined immunohistochemical profiles of ER/PR/HER2 and ER/PR/HER2/Ki-67 biomarkers respectively, revealed five immunohistochemical-based subtypes. These subtypes were ER-positive luminal A (ER+/±PR+/HER2-) [5.56%], ER-positive luminal B (ER+/±PR+/HER2+) [5.56%], HER2-overexpression (ER-/±PR+/HER2+) [16.66%], Triple negative (ER-/PR-/HER2-) [66.67%] and Unclassified subtypes (ER-/PR+/HER2-) [5.56%]. Furthermore, these five subtypes were further subcategorized into low (Ki-67 <20%) and high (Ki-67 ≥20%) proliferation subtypes accordingly. Conclusion: The commonest pattern of immunohistochemical profile expression of IDC in Uyo was found to be the Triple negative subtype.

Carcinoma del conducto salival: estudio clínico/patológico e inmunohistoquímico de 5 casos / Salivary duct carcinoma: a clinicopathologic and inmunohistochemical study of 5 cases

El carcinoma del conducto salival es un tumor epitelial maligno agresivo, que involucra principalmente a la glándula parótida, con características histológicas semejantes al carcinoma ductal de glándula mamaria. El propósito de este trabajo fue presentar los resultados clínico-patológicos de cinco casos de carcinoma del conducto salival primario de glándula parótida y evaluar la expresión de Ki67. Histológicamente, el carcinoma del conducto salival presentó nidos epiteliales con patrones papilar, sólido y cribiforme, comedonecrosis tanto en la lesión primaria como en los nodos linfoides metastásicos y, además, invasión perineural. Se demostró con Ki 67 una alta proliferación celular en cuatro (80 %) de los cinco casos estudiados. Se concluyó que: el carcinoma del conducto salival es una lesión maligna de mal pronóstico, raramente informado en la literatura odontológica, con características histológicas semejantes a las del carcinoma ductal de alto grado de la mama; la comedonecrosis es un signo específico de esta enfermedad; puede desarrollarse "de novo" o en un adenoma pleomórfico preexistente; su diagnóstico diferencial histopatológico es fundamental para planificar su tratamiento y determinar su pronóstico, a pesar de su tratamiento quirúrgico y radioterapia postoperatoria es un tumor agresivo con alta proliferación celular, infiltración perineural, recurrencias y metástasis.

Salivary duct carcinoma is an aggressive malignant epithelial tumor, primarily involving the parotid gland, with histologic features similar to ductal carcinoma of the breast. The purpose of this work was to report the clinicopathological results of five cases of primary salivary duct carcinoma of the parotid gland and evaluate the expression of Ki67. Histologically, salivary duct carcinoma presented epithelial nests with papillary, solid, and cribriform patterns, with comedonecrosis in both the primary lesion and the metastatic limph nodes, and perineural invasion. A high cell proliferation was demonstrated with Ki67 in four (80 %) of the five cases studied. We concluded that: salivary duct carcinoma is a malignant lesion with a poor prognosis, rarely reported in the dental literature, with histological characteristics similar to those of high-grade ductal carcinoma of the breast; comedonecrosis is a specific sign of this disease; may develop "de novo" or in a pre-existing pleomorphic adenoma; its differential histopathological diagnosis is essential to plan its treatment and determine its prognosis; despite its surgical treatment and postoperative radiotherapy, it is an aggressive tumor with high cell proliferation, perineural infiltration, recurrences and metastasis.

Análisis comparativo del Carcinoma Lobulillar Invasor versus Carcinoma Ductal Invasor: ¿entidades clínica o biológicamente diferentes? / Comparative analysis of Invasive Lobular Carcinoma versus Invasive Ductal Carcinoma: clinically or biologically different entities?

Introducción El Carcinoma Lobulillar Invasor (cli) es el tipo histológico especial más común del cáncer de mama. Presenta características histopatológicas asociadas a buen pronóstico, pero algunos estudios sugieren que los resultados a largo plazo pueden ser peores que los del Carcinoma Ductal Invasor (cdi). Objetivo Los objetivos principales del estudio fueron evaluar las características clínico-patológicas del cli y establecer el valor pronóstico. Material y método Se seleccionaron 244 pacientes con cli y se utilizó como grupo control a 524 pacientes con cdi, comparándolas con relación 2 a 1. Resultados No se observaron diferencias en edad, estado menopáusico, motivo de consulta e invasión linfovascular. Fueron más frecuentemente multifocales, multicéntricos, de mayor tamaño, bajo grado histológico y her2 negativo. La cirugía conservadora se realizó con menos frecuencia. No hubo diferencias significativas en recaída a distancia, cáncer de mama contralateral, sobrevida libre de enfermedad y global. Conclusiones Las pacientes con cli no tuvieron mejores resultados a pesar de un fenotipo biológico más favorable. La histología ductal o lobulillar no debería ser un factor en el manejo de la patología, y no debería considerarse un factor pronóstico o predictivo determinante al momento del diagnóstico

Introduction Invasive Lobular Carcinoma (ilc) is the second most common histologic type of breast cancer. Typically, displays features associated with a good prognosis, but some studies suggest that outcomes of ilc may be worse than for Invasive Ductal Carcinoma (idc). Objective The main purpose of this study was to evaluate the clinical-pathological characteristics of Lobular Breast Carcinoma and establish his prognostic value. Materials and method We selected a group of 244 patients with ilc and compared with 524 patients whit idc in relation 2:1. Results There were no differences in age, menopausal status, symptoms at time of diagnosis, and lymph vascular invasion. ilc were larger, low histological grade and her2 negative, more often mulfifocal and multicentric. Breast-preservation therapy was less frequent for Invasive Lobular Carcinoma. Distant relapse, contralateral cancer, overall survival, disease-free survival, did not differ between idc and ilc. Conclusions Women with ilc do not have better clinical outcomes than patients with idc, despite the fact that the biologic phenotype of ilc is quite favorable. The ductal or lobular histology should not be a factor in the therapeutic decision-making process, and should not be considered an important prognostic or predictive factor at diagnosis

Downregulation of N-myc and STAT Interactor Protein Predicts Aggressive Tumor Behavior and Poor Prognosis in Invasive Ductal Carcinoma / 한국유방암학회지

PURPOSE: We investigated the expression of the N-myc and STAT interactor (NMI) protein in invasive ductal carcinoma tissue and estimated its clinicopathologic significance as a prognostic factor. The expression levels and prognostic significance of NMI were also analyzed according to the molecular subgroup of breast cancers.METHODS: Human NMI detection by immunohistochemistry was performed using tissue microarrays of 382 invasive ductal carcinomas. The correlation of NMI expression with patient clinicopathological parameters and prognostic significance was analyzed and further assessed according to the molecular subgroup of breast cancers. Moreover, in vitro experiments with 13 breast cancer cell lines were carried out. We also validated NMI expression significance in The Cancer Genome Atlas cohort using the Human Protein Atlas (HPA) database.RESULTS: Low NMI expression was observed in 190 cases (49.7%). Low NMI expression was significantly associated with the “triple-negative” molecular subtype (p < 0.001), high nuclear grade (p < 0.001), high histologic grade (p < 0.001), and advanced anatomic stage (p = 0.041). Patients with low NMI expression had poorer progression-free survival (p = 0.038) than patients with high NMI expression. Low NMI expression was not significantly associated with patient prognosis in the molecular subgroup analysis. In vitro, a reduction of NMI expression was observed in 8 breast cancer cell lines, especially in the estrogen receptor-positive and basal B type of triple-negative breast cancer molecular subgroups. The HPA database showed that low NMI expression levels were associated with a lower survival probability compared with that associated with high NMI expression (p = 0.053).CONCLUSION: NMI expression could be a useful prognostic biomarker and a potential novel therapeutic target in invasive ductal carcinoma.

Caracterización histopatológica del cáncer de mama infiltrante HER2 positivo en el Hospital Hermanos Ameijeiras / Histopathological description of HER2 Positive Infiltrating Breast Cancer at Hermanos Ameijeiras Hospital

RESUMEN Introducción: La sobreexpresión del HER2 en el carcinoma de mama está asociada a un curso clínico adverso y menor sobrevida por lo que resulta necesario determinar las características histopatológicas presentes en el carcinoma de mama infiltrante en las pacientes que lo padecen, con el fin de establecer una terapéutica correcta e individualizada. Objetivos: Determinar las características histopatológicas más frecuentes presentes en el carcinoma de mama con sobreexpresión del gen HER2. Métodos: Estudio observacional, transversal en el período de enero 2010 a diciembre 2012. Se incluyeron 93 pacientes. Se exploraron variables sociodemográficas, clínicas e hstopatológicas. En el análisis estadístico se utlizaron frecuenicas absolutas y relativas. Resultados: La media de edad fue de 55,1 años y el 68,8 por ciento era de piel blanca. La mama más afectada fue la derecha con el 45,2 por ciento y la localización más frecuente el cuadrante supero-externo con el 26,9 por ciento. El carcinoma ductal invasivo representó el 71 por ciento del total. El grado nuclear 3 se encontró en 81,7 por ciento casos y la necrosis tumoral 88,2 por ciento. Los receptores estrogénicos fueron positivos en 50,5 por ciento y los receptores de progesterona fueron negativos en 59,1 por ciento. El análisis histológico del cáncer de mama será de utilidad para individualizar la terapia de cada una de las pacientes. Conclusiones: Es importante continuar la investigación con la incorporación de otras variables de interés, tales como, respuesta al tratamiento y supervivencia, además de la prueba de hibridización in situ detectada por fluorescencia en las pacientes del universo en las que se constató HER2 2+ para definir su estatus y orientar mejor su tratamiento(AU)

ABSTRACT Introduction: HER2 overexpression in breast carcinoma is associated with the adverse clinical course and shorter survival, so it is necessary to determine the histopathological characteristics present in infiltrating breast carcinoma in patients with it, in order to establish correct and individualized therapy. Objectives: To determine the histopathological characteristics that are most frequently present in breast carcinoma with overexpression of HER2 gene in the studied patients. Methods: Observational, cross-sectional study from January 2010 to December 2012. Nine three patients were included. Sociodemographic, clinical, and pathological variables were explored. Absolute and relative frequencies were used in the statistical analysis. Results: The mean age was 55.1 years; 68.8 percent were white skinned. The most affected breast was the right one in 45.2 percent and the most frequent location was the upper-external quadrant in 26.9 percent. Invasive ductal carcinoma represented 71 percent of the total. Nuclear grade 3 was found in 81.7 percent cases and tumor necrosis 88.2 percent. Estrogen receptors were positive in 50.5 percent and progesterone receptors were negative in 59.1 percent. Histological analysis of breast cancer will be useful to individualize the therapy of each patient. Conclusions: It is important to continue the investigation with the incorporation of other variables of interest, such as response to treatment and survival, in addition to the in situ hybridization test detected by fluorescence in the patients of the universe in which HER2 2+ was found to define the status and better guide the treatment(AU)

Adenopatía axilar metastásica a causa de cáncer primario oculto de mama / Axillary metastatic adenopathy due to hidden breast primary cancer

Se describe el caso clínico de una paciente de 56 años que acudió a la consulta de Oncología del Hospital Gubernamental de Mbabane, en Swazilandia, por padecer una adenopatía en la axila izquierda de varios meses de evolución, confirmada por ecografía. Se realizó una biopsia por aspiración con aguja fina, cuyo resultado reveló la metástasis de un carcinoma ductal. Se completaron los estudios preoperatorios, se determinó el estadio de la entidad clínica (IIA) y se remitió a la paciente a la consulta de Cirugía para realizar una disección axilar y luego aplicar radioterapia en la axila y la mama

The clinical report of a 56 year-old patient who went to the Oncology Service of the Government Hospital from Mbabane, in Swaziland, for suffering an adenopathy in the left armpit with a clinical course of several months, confirmed by echography is described. An aspiration biopsy with fine needle was carried out whose result revealed the metastasis of a ductal carcinoma. The preoperative studies were completed, the stage of the clinical entity was determined (IIA) and the patient was referred to the Surgery service to carry out an axillary dissection and then to apply radiotherapy in the armpit and breast

Reverse Warburg Effect-Related Mitochondrial Activity and ¹⁸F-FDG Uptake in Invasive Ductal Carcinoma / 대한핵의학회잡지

PURPOSE: We evaluated the relationship between fluorine-18 fluoro-2-deoxy-glucose (¹⁸F-FDG) uptake and mitochondrial activity in cancer cells and investigated the prognostic implications of this relationship in patients with invasive ductal carcinoma of the breast (IDCB).METHODS: One hundred forty-six patients with primary IDCB who underwent preoperative ¹⁸F-FDG PET/CT followed by curative surgical resection were enrolled in the current study. Mitochondrial activity of cancer cells was assessed based on translocase of outer mitochondrial membrane 20 (TOMM20) expression and cytochrome C oxidase (COX) activity. A Pearson's correlation analysis was used to assess the relationship between the maximum standardized uptake value of the primary tumour (pSUVmax) and mitochondrial activity. Clinicopathological factors, including pSUVmax, histological grade, oestrogen receptor (ER), progesterone receptor (PR), and TOMM20 expression; and COX activity, were assessed for the prediction of disease-free survival (DFS) using the Kaplan–Meier method and Cox proportional hazards model.RESULTS: Fourteen of the 146 subjects (9.6%) showed tumour recurrence. There was a significant positive correlation between ¹⁸F-FDG uptake and the mitochondrial activity of cancer cells in patients with IDCB, and increased ¹⁸F-FDG uptake and mitochondrial activity were significantly associated with a shorter DFS. Additionally, results from the receiver-operating curve analysis demonstrated that the cut-off values of pSUVmax, TOMM20 expression, and COX activity for the prediction of DFS were 7.76, 4, and 5, respectively. Further, results from the univariate analysis revealed that pSUVmax, TOMM20 expression, PR status, and histologic grade were significantly associated with DFS; however, the multivariate analysis revealed that only pSUVmax was associated with DFS (HR, 6.51; 95% CI, 1.91, 22.20; P = 0.003).CONCLUSIONS: The assessment of preoperative ¹⁸F-FDG uptake and post-surgical mitochondrial activity may be used for the prediction of DFS in patients with IDCB.

Generalized Cutaneous Metastasis of Breast Ductal Carcinoma / 대한피부과학회지

No abstract available.

Human Epidermal Growth Factor Receptor 2-Subtype Invasive Ductal Carcinoma Recurring as Basal-Human Epidermal Growth Factor Receptor 2-Subtype Squamous Cell Carcinoma / 한국유방암학회지

Squamous cell carcinoma of the breast and its subtype, basal-human epidermal growth factor receptor 2 (HER2) phenotype, are very rare. Herein, we report a patient who developed recurrence of squamous cell carcinoma of the breast with basal-HER2 subtype 6 years after the initial diagnosis of invasive ductal carcinoma of the HER2 subtype. To the best of our knowledge, recurrence of invasive ductal carcinoma in the form of metaplastic squamous cell carcinoma of basal-HER2 subtype has not been reported previously. We present a pathological perspective of our experience.

The Correlation between IL-1β-C31T Gene Polymorphism and Susceptibility to Breast Cancer / 한국유방암학회지

PURPOSE: Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, has been shown to influence breast cancer susceptibility. The relationship between its risk of breast cancer and IL-1β-C31T polymorphism has been demonstrated, but the results remain controversial. Therefore, our study aimed to investigate the correlation between the IL-1β-C31T gene polymorphism and susceptibility to breast cancer. METHODS: The genotype frequencies of IL-1β-C31T polymorphism were compared between 204 breast cancer cases and 210 controls using polymerase chain reaction and restriction fragment length polymorphism techinques. Further multivariate binary logistic regression analyses were used to assess the association between IL-1β-C31T polymorphism and breast cancer risk. RESULTS: The frequency of the T allele of IL-1β-C31T polymorphism in breast cancer cases was significantly higher than that in the controls (56.1% vs. 47.9%). The frequencies of genotypes CC, CT, and TT in the cases were 22.1%, 43.6%, and 34.3%, respectively, while in the control group they were 24.3%, 55.7%, and 20.0%, respectively. There was a significant difference between the prevalence of TT genotype in the 2 groups (adjusted odds ratio [OR], 2.06; 95% confidence interval [CI], 1.16–3.66; p  =  0.014). Breast cancer risk increased in women with TT genotype, body mass index (BMI) ≥ 25 kg/m2 (OR, 2.19; 95% CI, 1.09–4.36), late age at first birth (OR, 2.43; 95% CI, 1.29–4.56), postmenopausal status (OR, 3.15; 95% CI, 1.39–7.16), and negative smoking history (OR, 2.52; 95% CI, 1.32–4.82). Furthermore, increase in breast cancer risk among women diagnosed with invasive ductal carcinoma was associated with CT/TT genotypes (OR, 2.82; 95% CI, 1.38–5.76). CONCLUSION: The IL-1β-C31T polymorphism affects breast cancer susceptibility, especially in women with late age at first birth, high BMI, postmenopausal status, negative smoking history, and invasive ductal carcinoma. Our study adds to the evidence about the importance of IL-1β-C31T polymorphism in breast cancer susceptibility.

Comparative Analysis of Outcomes and Clinicopathological Characteristics of Synchronous and Metachronous Contralateral Breast Cancer: A Study of the SEER Database / 한국유방암학회지

PURPOSE: Numerous previous studies have reported inconsistent results about the differences between synchronous contralateral breast cancer (sCBC) and metachronous contralateral breast cancer (mCBC). This study aimed to compare the clinical characteristics and outcomes between sCBC and mCBC and determine predictive factors for the survival of sCBC and mCBC patients. METHODS: Using the Surveillance, Epidemiology, and End Results Program database, we identified sCBC or mCBC patients from 2000 to 2010. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to analyze overall survival and breast cancer-specific survival (BCSS) rates of sCBCs and mCBCs, respectively. RESULTS: Overall, 14,057 sCBC (n = 8,139, 57.9%) and mCBC (n = 5,918, 42.1%) patients were included. The first tumors of sCBC were more likely to have higher stage and more lymph and distant metastases, whereas those of mCBC were more often infiltrating ductal carcinoma (IDC), had localized stage, were estrogen receptor (ER) and progesterone receptor (PR) negative, and had less axillary nodal involvement. The second tumors of mCBC tended to be IDC and have higher grade, adverse stage, ER and PR-negativity; and more axillary nodal involvement, compared to the second tumors of sCBC. mCBC patients had significantly favorable 5-year BCSS but worse long-term BCSS compared with sCBC patients. Moreover, subgroup analysis revealed no significant difference of BCSS between sCBC and mCBC among patients aged 18–60 years. Multivariate analysis indicated that age, grade, and stage of 2 tumors; surgery for second tumor; and ER status of the second tumor were independent prognostic factors for BCSS of contralateral breast cancer (CBC). CONCLUSION: The characteristics and outcomes of sCBCs and mCBCs were substantially different. sCBC and mCBC patients may have different prognosis, and the prognosis of CBC depends on the first and second tumors.

Prediction of Axillary Lymph Node Metastasis in Early Breast Cancer Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Diffusion-Weighted Imaging

PURPOSE: The purpose of this study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) variables, for axillary lymph node (ALN) metastasis in the early stage of breast cancer. MATERIALS AND METHODS: January 2011–April 2015, 787 patients with early stage of breast cancer were retrospectively reviewed. Only cases of invasive ductal carcinoma, were included in the patient population. Among them, 240 patients who underwent 3.0-T DCE-MRI, including DWI with b value 0 and 800 s/mm² were enrolled. MRI variables (adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, quantitative kinetic parameters, signal enhancement ratio (SER), tumor apparent diffusion coefficient (ADC), peritumoral ADC, and peritumor-tumor ADC ratio) clinico-pathologic variables (age, T stage, multifocality, extensive intraductal carcinoma component (EIC), estrogen receptor, progesterone receptor, HER-2 status, Ki-67, molecular subtype, histologic grade, and nuclear grade) were compared between patients with axillary lymph node metastasis and those with no lymph node metastasis. Multivariate regression analysis was performed, to determine independent variables associated with ALN metastasis, and the area under the receiver operating characteristic curve (AUC), for predicting ALN metastasis was analyzed, for those variables. RESULTS: On breast MRI, moderate or prominent ipsilateral whole-breast vascularity (moderate, odds ratio [OR] 3.45, 95% confidence interval [CI] 1.28–9.51 vs. prominent, OR = 15.59, 95% CI 2.52–96.46), SER (OR = 1.68, 95% CI 1.09–2.59), and peritumor-tumor ADC ratio (OR = 6.77, 95% CI 2.41–18.99), were independently associated with ALN metastasis. Among clinico-pathologic variables, HER-2 positivity was independently associated, with ALN metastasis (OR = 23.71, 95% CI 10.50–53.54). The AUC for combining selected MRI variables and clinico-pathologic variables, was higher than that of clinico-pathologic variables (P < 0.05). CONCLUSION: SER, moderate or prominent increased whole breast vascularity, and peritumor-tumor ADC ratio on breast MRI, are valuable in predicting ALN metastasis, in patients with early stage of breast cancer.

An Updated Nomogram for Predicting Invasiveness in Preoperative Ductal Carcinoma In Situ of the Breast

PURPOSE: To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. MATERIALS AND METHODS: Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer—Lemeshow goodness of fit test. RESULTS: The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. CONCLUSION: The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.

Feasibility of ultrasound-guided absorbable retaining thread needle localization for nonpalpable breast lesions

PURPOSE: Absorbable retaining thread (ART) needle localization utilizes a guiding needle with a thread; this technique was invented to reduce patient discomfort and wire migration. We investigated the feasibility of ultrasound (US)-guided ART needle localization for nonpalpable breast lesions. METHODS: ART needle localization was performed for 26 nonpalpable breast lesions in 26 patients who were scheduled to undergo surgical excision the day after localization. Seventeen breast lesions were initially diagnosed as invasive ductal carcinoma, six as ductal carcinomas in situ, and one as fibrocystic change. The other two cases without an initial pathologic diagnosis had suspicious US features, and excision was planned concomitantly with contralateral breast cancer surgery. The primary outcome was the technical success rate of ART needle localization confirmed by US immediately after the procedure, and the secondary outcomes were the percentage of clear margins on pathology and the complication rate of ART needle localization. RESULTS: The technical success rate of ART needle localization was 96.2% (25 of 26 patients), and the ART was located 1 cm away from the mass in one patient (3.8%). The lesions were successfully removed with clear margins in all 26 patients. No significant complications related to ART needle localization were observed. CONCLUSION: ART needle localization can be an alternative to wire needle localization for nonpalpable breast lesions.

Early experiences with robot-assisted prosthetic breast reconstruction

Robotic surgery facilitates surgical procedures by employing flexible arms with multiple degrees of freedom and providing high-quality 3-dimensional imaging. Robot-assisted nipplesparing mastectomy with immediate reconstruction is currently performed to avoid breast scars. Four patients with invasive ductal carcinoma underwent robot-assisted nipple-sparing mastectomy and immediate robot-assisted expander insertion. Through a 6-cm incision along the anterior axillary line, sentinel lymph node biopsy and nipple-sparing mastectomy were performed by oncologic surgeons. The pectoralis major muscle was elevated, an acellular dermal matrix (ADM) sling was created with robotic assistance, and an expander was inserted into the subpectoral, sub-ADM pocket. No patients had major complications such as hematoma, seroma, infection, capsular contracture, or nipple-areolar necrosis. The mean operation time for expander insertion was 1 hour and 20 minutes, and it became shorter with more experience. The first patient completed 2-stage prosthetic reconstruction and was highly satisfied with the unnoticeable scar and symmetric reconstruction. We describe several cases of immediate robot-assisted prosthetic breast reconstruction. This procedure is a feasible surgical option for patients who want to conceal surgical scars.

Omission of Chemotherapy for the Treatment of Mucinous Breast Cancer: A Nationwide Study from the Korean Breast Cancer Society / 한국유방암학회지

Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). MATERIALS AND METHODS: Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed. RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs. CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer / 한국유방암학회지

PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological para-meters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. METHODS: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. RESULTS: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases ( 51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p < 0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p < 0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p < 0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296–0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314–0.3912; p=0.0006). CONCLUSION: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

Tamoxifen-Induced Non-alcoholic Steatohepatitis Cirrhosis

Non-alcoholic fatty liver disease has been observed in over 30% of patients who have received tamoxifen therapy. However, tamoxifen-induced non-alcoholic steatohepatitis (NASH) cirrhosis has never been reported in Korea. A 41-year-old woman was diagnosed with invasive ductal carcinoma in the left breast. She had well-controlled type 2 diabetes mellitus, hypertension, and chronic hepatitis B. Ultrasonography showed mild fatty liver. Chronic hepatitis B had been treated with clevudine one month before the diagnosis of breast cancer. The patient was diagnosed with NASH cirrhosis 39 months after tamoxifen treatment. Careful observation for the development of NASH cirrhosis is warranted during tamoxifen therapy.