PURPOSE: This study aimed to evaluate the usefulness of the axillary lymph node to primary breast tumor maximum standardized uptake value (SUVmax) ratio in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for predicting the presence of metastasis in axillary lymph nodes. METHODS: Herein, 196 consecutive patients with breast cancer who underwent PET/CT before surgery from January 2009 to January 2013 were included. We calculated the axillary lymph node to primary breast tumor SUVmax ratio using PET/CT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ratio were compared with those of nodal SUVmax and axillary ultrasonography. Axillary node metastasis was confirmed with sentinel node biopsy or axillary dissection. RESULTS: The SUVmax ratio (cutoff, 0.14; area under the curve, 0.741) had 55.4% sensitivity, 91.6% specificity, 76.6% PPV, and 80.5% NPV for predicting axillary node metastasis. No significant difference was observed in terms of predicting axillary node metastasis among the SUVmax ratio, nodal SUVmax, and ultrasonography. In the multivariate analysis, primary tumor size (p=0.014), SUVmax of the primary tumor (p=0.011), axillary ultrasonography findings, nodal SUVmax, and SUVmax ratio were significantly associated with lymph node metastasis (p<0.001). CONCLUSION: The axillary lymph node to primary breast tumor SUVmax ratio predicted axillary lymph node metastasis, although no significant difference in diagnostic performance was observed between PET/CT and ultrasonography. The axillary lymph node to primary breast tumor SUVmax ratio may be considered an additional method for the preoperative evaluation of axillary lymph node status.

PURPOSE: The purpose of this study was to determine whether magnetic resonance imaging (MRI) could assess the size of ductal carcinoma in situ (DCIS) more accurately compared to mammography and ultrasonography using the histopathological dimension of the surgical specimen as the reference measurement. METHODS: This was a retrospective review study using data from our institution database of breast cancer. Preoperative contrast-enhanced MRI, mammography and ultrasonography were performed to detect and assess the size of DCIS in 131 patients. The greatest dimensions of DCIS determined by the imaging modalities were compared with the histopathological dimensions of the surgical specimens. Intraclass coefficients were calculated to examine the agreement among the MRI, mammography and ultrasonography measurements. The Wilcoxon signed-rank test was used to evaluate the statistical significance of the differences in size among MRI, mammography or ultrasonography and histopathology findings. RESULTS: Of the 131 DCIS lesions, 126 (96.2%) were detected by MRI, 103 (78.6%) were detected by mammography, and 121 (92.4%) were detected by ultrasonography. The mean lesion size was 38.8 mm on histopathology, 36.0 mm on MRI, 28.8 mm on mammography, and 23.3 mm on ultrasonography, and there were no significant differences between sizes determined by histopathology and MRI, while there were significant differences between histopathology and the other modalities. The correlation coefficient between histopathological measurement and MRI was 0.837, versus 0.461 between histopathology and mammography and 0.284 between histopathology and ultrasonography. The lesion size was correctly estimated (±5 mm), under-estimated (<5 mm), or over-estimated (>5 mm), respectively, by MRI in 52.7%, 30.5%, and 16.8% of cases; by mammography in 32.0%, 51.2%, and 16.8% of cases, respectively; and by ultrasonography in 24.4%, 62.6%, and 13.0% of cases, respectively. CONCLUSION: In our study, MRI was more accurate for detection and assessment the size of DCIS compared to mammography and ultrasonography.

PURPOSE: Obesity in women has been shown to have correlation with breast cancer incidence. The proportion of Korean women who are obese has increased recently. However, there is no large-scale study evaluating the relationship between obesity and breast cancer incidence in Korea. In this study, we tried to identify the relationship between obesity and breast cancer incidence in Korean women by using body mass index (BMI). METHODS: A retrospective analysis was performed using single-center data of 28,631 patients screened with breast ultrasonography or mammography between January 2009 to December 2013 in Seoul National University Hospital Healthcare System Gangnam Center. Their clinical characteristics were evaluated. The correlations between breast cancer incidence with BMI and other factors were analyzed using univariate and multivariate logistic regression models. RESULTS: A total of 28,631 patients were enrolled; 67 patients were diagnosed with breast cancer. Among patients without breast cancer, the proportion of patients with BMI under 23 was 68.1%, whereas it was 56.7% among patients with breast cancer (p=0.036). In univariate analysis, patients with a BMI over 25 had an odds ratio of 2.09 for breast cancer compared with those with a BMI under 23 (p=0.012). In addition, patients with a waist circumference over 85 cm had an odds ratio of 1.69 for breast cancer compared with the others (p=0.042). In multivariate analysis, BMI also had significant correlation with breast cancer incidence (odds ratio=1.87, p=0.035). CONCLUSION: An increase in BMI has positive correlation with breast cancer incidence in Korean women. However, a multi-centered prospective study is needed for further evaluation.

PURPOSE: Few studies have reported postdiagnosis differences in distress and quality of life (QOL) for breast cancer (BC) survivors. Here we investigated the differences in distress and QOL for BC survivors in Korea, during follow-up. METHODS: Completed questionnaires were collected from 179 BC survivors in 2013. Functional Assessment of Cancer Therapy-Breast was administered to measure the distress and Distress Thermometer and Problem List was administered to measure the QOL. RESULTS: The mean QOL score was 96.69 (standard deviation, ±20.33). Seventy-nine patients (44.1%) with distress-test scores >4 were assigned to the severe distress group. The patient group with higher family income had high QOL score (p=0.008). In addition, QOL scores were significantly higher in patients who lived longer after diagnosis (p=0.016). Patients at high TNM stage had low QOL scores (p=0.006). Furthermore, older patients tended to have high distress scores (p=0.028). Based on duration of the postdiagnosis period, we divided the patients into two groups. Seventy patients had a postdiagnosis period <2 years; 109 patients, postdiagnosis period ≥2 years. Distress score of the under-2-year group (4.26±2.73) was significantly higher (p=0.044) than that of the longer-than-2-year group (3.47±2.42). CONCLUSION: BC survivors showed improvement in physical well-being, emotional well-being, and functional well-being domain of QOL over time. However, social well-being and BC subscale score were only slightly improved over time. It is possible that cancer patients' supporting programs are focused on the recently diagnosed patients or those currently undergoing treatment. Therefore, more support should be made available to long-term BC survivors.

PURPOSE: The molecular subtype of breast cancer is an important predictive factor. Therefore, we investigated the effects of concurrent or serial radiotherapy and systemic therapy on metastatic brain lesions according to the molecular subtype of breast cancer. METHODS: The present retrospective study examined data from 66 patients with breast cancer and metastatic brain lesions, who were treated using radiotherapy between January 1990 and July 2014. Patients were classified into the following three subtypes based on their hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status: HR+/HER2− (luminal A, 13 patients), HR+/HER2+ (luminal B, 21 patients), HR−/HER2+ (HER2, 22 patients), or HR−/HER2− (triple negative, 10 patients). The brain lesions and their responses to treatment were evaluated using brain computed tomography or magnetic resonance imaging. Progression of brain disease was defined by a ≥20% increase in the sum of the lesion's diameters or the development of a new brain lesion. Progression-free survival was calculated from the initiation of radiotherapy to the first instance of brain disease progression or last follow-up. RESULTS: Patients in the HER2 group who had received concur-rent radiotherapy and systemic therapy (mainly HER2-targeted therapy) exhibited significantly better progression-free survival than did patients who had received radiotherapy followed by systemic therapy (p=0.037). However, concurrent radiotherapy and systemic therapy did not significantly improve progression-free survival in the luminal A (p=0.527), luminal B (p=0.462), or triple negative (p=0.558) groups. CONCLUSION: Concurrent radiotherapy and mainly HER2-targeted systemic therapy significantly prolonged progression-free survival in the HER2 group.

PURPOSE: The preoperative determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and Ki-67 expression status is crucial because these factors influence the therapeutic response to endocrine therapy, chemotherapy, and HER2-targeted therapy and help in the selection of adjuvant or neoadjuvant treatment. To evaluate the accuracy of core needle biopsy (CNB) in determining ER, PR, and HER2 status, and Ki-67 level status, we compared the results of CNB with those of surgical specimens. METHODS: We retrospectively reviewed data from 191 patients with breast cancer whose ER, PR, and HER2 status, and Ki-67 level status was analyzed using both CNB and surgical specimens between 2013 and 2015. Patients who received neoadjuvant chemotherapy were excluded from this study. ER, PR, and Ki-67 were detected using immunohistochemistry (IHC) and reported as the percentage of positively stained cells. The cutoff point was 1% for ER and PR, and 14% for Ki-67. HER2 was determined by IHC and/or fluorescence in situ hybridization (FISH). HER2 positivity was defined as IHC 3+ or FISH (+). RESULTS: In correlation analysis, Pearson correlation coefficients were 0.950 for ER expression, 0.813 for PR expression, 0.847 for HER2 grade, and 0.817 for Ki-67 expression level (p<0.0001). According to criteria for ER, PR, HER2, and Ki-67, the sensitivities of ER, PR, HER2, and Ki-67 assessment in CNB were 92.6%, 88.8%, 100%, and 80.6%, respectively. The specificities of ER, PR, HER2, and Ki-67 assessments in CNB were 90.7%, 86.0%, 99.1%, and 88.7%, respectively. CONCLUSION: The ER, PR, HER2, and Ki-67 status in CNB specimens correlated well with their status in surgical specimens. The HER2 status was the most accurately assessed factor in CNB specimens when compared to its assessment in surgical specimens. However, Ki-67 levels in CNB specimens were lower than those in surgical specimens.

PURPOSE: Larger tumor size and more extensive lymph node (LN) involvement have been considered independent factors for poor prognosis of breast cancer. We evaluated whether smaller tumor size may be a factor of worse prognosis compared with larger tumor size in small-sized breast cancer with LN involvement. METHODS: A retrospective analysis was conducted at a single center for 1,400 patients with small-sized (≤2 cm) and LN involved (N1–N3) breast cancer who underwent radical surgery, had no distant metastases, and were diagnosed between 2004 and 2014. We subdivided their tumor size into four subgroups (T1mi, T1a, T1b, T1c) graded using the 7th American Joint Committee on Cancer staging and two subgroups (T1ab [≤1 cm] and T1c [>1 cm]) divided by tumor size. The relationship between tumor size, prognosis and specific features were analyzed using the Chi-square test, Kaplan-Meier method, and Cox regression analysis. RESULTS: There were significant differences in estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2) and HER2 amplified type among the four subgroups in all patients. Especially, HER2-amplified type also appeared in distribution significantly between the two subgroups in all patients (T1ab [13.0%] vs. T1c [8.0%], p=0.008). The overall survival of the T1N1 staged patients in the smaller-sized tumor group (T1ab) was lower than that of those in the larger-sized group (T1c) (p=0.005). In the multivariate Cox regression analysis of all patients, the T1ab group showed a higher mortality risk compared with the T1c group (adjusted hazard ratio, 2.540; 95% confidence interval, 1.195–5.397; p=0.015). CONCLUSION: Smaller-sized tumors with LN involvement indicated worse prognosis compared with larger-sized tumors.

PURPOSE: Sentinel lymph node biopsy (SLNB) has been a reliable technique in breast cancer staging. However, some authors reported that SLNB after neoadjuvant chemotherapy (NAC) could lead to low identification rates and high false-negative rates. Hence, whether only SLNB can be applied after NAC is controversial. The aim of this study was to identify predictive factors of residual metastatic axillary lymph nodes after NAC. METHODS: In this study, 71 breast cancer patients with clinically positive lymph nodes (cN1), who received axillary lymph node dissection (ALND) after NAC between July 2012 and September 2014, were enrolled. The patients were divided into N1 and N0 groups according to the presence of residual axillary metastatic lymph nodes after ALND. We compared the clinical, radiological, and immunohistological factors between two groups. RESULTS: In the 71 patients with cN1who received NAC, N1 and N0 status were confirmed after surgery in 43 and 28 patients, respectively. The clinical stage at diagnosis was IIA in one patient, IIB in 15 patients, IIIA in 35 patients, IIIB in two patients, IIIC in 10 patients, and IV in eight patients. Most of the patients (n=57) received eight cycles (four cycles of anthracycline and four of taxane) of chemotherapy. Our study showed that the primary tumor was downstaged in 58 of the 71 patients (81.7%). Sixteen patients (22.5%) had pathological complete response (pCR) and 42 (59.2%) had pathological partial response. In a multivariate analysis, tumor response and human epidermal growth factor receptor 2 (HER2) were identified as significant factors. However, no significant differences were observed in the results of postchemotherapy ultrasonography, and pre- or post-positron emission tomography computed tomography (maximum standardized uptake value reduction). CONCLUSION: In the NAC setting, SLNB before ALND is feasible for tumors predicted to have a pCR or if target therapy had been administered for HER2-positive breast cancer.

PURPOSE: Breast cancer is the most common invasive cancer and the second common cause of death among women worldwide. Many researchers have focused on the effective treatment of advanced breast cancer using new drugs. Herein, we analyzed whether PLX4032, a B-RAF V600E inhibitor, could be used as a novel treatment for advanced breast cancer. METHODS: Two breast cancer cell lines, MCF7 and MDA-MB-231, were treated with the selective B-Raf inhibitor PLX4032 under adherent culture conditions and the effects of PLX4032 on cell growth, cell cycle duration, apoptosis and cell cycle related genes expression were evaluated. RESULTS: We found that PLX4032 dose-dependently inhibited cell growth in both cell lines through cell cycle arrest at phase G0/G1. However, PLX4032 treatment did not have a significant effect on cell apoptosis. In addition, CCNA2 gene expression was significantly decreased in the MCF7 cells in a dose-dependent manner. CONCLUSION: Our data demonstrated that treatment of breast cancer with PLX4032 could inhibit proliferation through cell cycle arrest. Therefore, PLX4032 might be a novel anticancer drug that can be used in the treatment of advanced breast cancer.

Cowden syndrome (CS), also known as multiple hamartomas syndrome, is a rare hereditary autosomal dominant disorder caused by a germline mutation in the phosphatase and tensin homolog (PTEN) gene mapped on chromosome 10. The clinical features of CS are variable, primarily presenting as mucocutaneous lesions (99%). A mucocutaneous lesion, such as trichilemmoma of the face or keratosis of the extremities, is an important diagnostic marker for CS. CS has been reported to increase the incidence of benign and malignant neoplasms in the breast, thyroid, and gastrointestinal tract. The risk of developing malignancy in individuals with CS is up to 10 times higher than general population throughout an entire life time.
Breast Neoplasms* ; Breast* ; Chromosomes, Human, Pair 10 ; Extremities ; Gastrointestinal Tract ; Germ-Line Mutation ; Hamartoma ; Hamartoma Syndrome, Multiple* ; Humans ; Incidence ; Keratosis ; Thyroid Gland