Long-term risk of congestive heart failure in younger breast cancer survivors: A nationwide study by the SMARTSHIP group.

BACKGROUND: There is a controversy about late-onset congestive heart failure (CHF) among breast cancer survivors. This study investigated the incidence rate and risk factors of late-onset CHF more than 2 years after the breast cancer diagnosis. METHODS: A nationwide, retrospective study was conducted with the National Health Information Database. With 1:3 age- and sex-matched noncancer controls, Cox proportional hazard regression models were used to analyze the incidence and risk factors of late CHF. The cumulative incidence rate of late CHF was evaluated with a Kaplan-Meier analysis and a log-rank test. RESULTS: A total of 91,227 cases (286,480 person-years) and 273,681 controls (884,349 person-years) were evaluated between January 2007 and December 2013. The risks of late CHF were higher in cases than controls (hazard ratio [HR], 1.396; 95% confidence interval [CI], 1.268-1.538). Younger survivors (age ≤ 50 years) showed a higher risk of late CHF than their younger counterparts (HR, 2.903; 95% CI, 2.425-3.474). Although older age was a risk factor for late CHF, older survivors (age ≥ 66 years) showed no difference in the risk of late CHF in comparison with their counterparts (HR, 0.906; 95% CI, 0.757-1.084). Anthracyclines and taxanes were risk factors for late CHF, although trastuzumab, radiation, and endocrine therapy were not. CONCLUSIONS: Young breast cancer survivors have a greater risk of late CHF than the young population without cancer. More attention should be paid to young breast cancer survivors who receive taxane- or anthracycline-based regimens over the long term.

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress.

BACKGROUND: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. METHODS: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. DISCUSSION: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR).

BACKGROUND: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. METHODS/DESIGN: Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. DISCUSSION: This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01589367.

Five-year changes in ovarian function restoration in premenopausal patients with breast cancer taking tamoxifen after chemotherapy: An ASTRRA study report.

BACKGROUND: Adding ovarian function suppression (OFS) after chemotherapy improves survival in young women with moderate- and high-risk breast cancer. Assessment of ovarian function restoration after chemotherapy becomes critical for subsequent endocrine treatment and addressing fertility issues. PATIENTS AND METHODS: In the adding OFS after chemotherapy trial, patients who resumed ovarian function up to 2 years after chemotherapy were randomised to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. Ovarian function was evaluated from enrolment to randomisation, and patients who did not randomise because of amenorrhoea for 2 years received tamoxifen and were followed up for 5 years. Prospectively collected consecutive hormone levels (proportion of patients with premenopausal follicle-stimulating hormone [FSH] levels <30 mIU/mL and oestradiol [E2] levels ≥40 pg/mL) and history of menstruation were available for 1067 patients with breast cancer. RESULTS: Over 5 years of tamoxifen treatment, 69% of patients resumed menstruation and 98% and 74% of patients satisfied predefined ovarian function restoration as per serum FSH and E2 levels, respectively. Menstruation was restored in 91% of patients younger than 35 years at baseline, but in only 33% of 45-year-old patients over 5 years. Among these patients, 41% experienced menstruation restoration within 2 years after chemotherapy and 28% slowly restored menstruation after 2-5 years. Younger age (<35 years) at baseline, anthracycline without taxanes and ≤90 days of chemotherapy were predictors of menstruation restoration. CONCLUSIONS: During 5 years of tamoxifen treatment after chemotherapy, two-thirds of the patients experienced menstruation restoration, especially patients younger than 35 years. Young age, Adriamycin without taxanes and short duration of chemotherapy appeared to have a positive effect on ovarian reserves in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00912548.

Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial.

PURPOSE: The addition of ovarian function suppression (OFS) for 5 years to tamoxifen (TAM) for treatment of premenopausal patients with breast cancer after completion of chemotherapy has beneficial effects on disease-free survival (DFS). This study evaluated the efficacy of adding 2 years of OFS to TAM in patients with hormone receptor-positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy. PATIENTS AND METHODS: We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor-positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. Ovarian function was assessed every 6 months for 2 years since enrollment on the basis of follicular-stimulating hormone levels and vaginal bleeding history. If ovarian function was confirmed to be premenopausal at each visit, the patient was randomly assigned to complete 5 years of TAM alone (TAM-only) group or 5 years of TAM with OFS for 2 years that involved monthly goserelin administration (TAM + OFS) group. DFS was defined from the time of enrollment to the time of the first event. RESULTS: A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis. The estimated 5-year DFS rate was 91.1% in the TAM + OFS group and 87.5% in the TAM-only group (hazard ratio, 0.69; 95% CI, 0.48 to 0.97; P = .033). The estimated 5-year overall survival rate was 99.4% in the TAM + OFS group and 97.8% in the TAM-only group (hazard ratio, 0.31; 95% CI, 0.10 to 0.94; P = .029). CONCLUSION: The addition of 2 years of OFS to TAM significantly improved DFS compared with TAM alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.

The effect of sex hormones on normal breast tissue metabolism: Evaluation by FDG PET/CT.

This study investigated the effect of sex hormones on F-fluorodeoxyglucose (FDG) uptake in normal breast tissue.The retrospective study included 249 premenopausal women (median age, 45 years) who were diagnosed with unilateral breast cancer and underwent FDG positron emission tomography/computed tomography and hormone tests. The volume of interest was within the contralateral normal breast and the standardized uptake values (SUVs) were measured. The correlations of sex hormones (including estrogen, progesterone, testosterone, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) with the SUVs of the normal breast were analyzed.There was a weak negative correlation between age and breast FDG uptake (P = .012, Spearman coefficient = -.16 for the maximum standardized uptake values [SUVmax]), especially in the luteal phase group (P = .005, Spearman coefficient = -.27 for SUVmax). The SUVs of normal breast tissue were increased when progesterone levels were higher (P = .043, Spearman coefficient = .13 for SUVmax). In the irregular menstrual cycle group, FDG uptake in the breast decreased as FSH (P = .027, Spearman coefficient = -.42 for SUVmax) and LH (P = .048, Spearman coefficient = -.44 for SUVmax) increased.Glucose metabolism of normal breast tissue decreases with age, and progesterone weakly affects breast FDG uptake. Gonadotropins may affect breast FDG uptake in premenopausal women with irregular menstrual cycles.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment.

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from -0.39 at baseline to -0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

Clinical Utility of Real-Time MR-Navigated Ultrasound with Supine Breast MRI for Suspicious Enhancing Lesions Not Identified on Second-Look Ultrasound.

This study evaluated the usefulness of magnetic resonance (MR)-navigated ultrasound (US) for evaluation of magnetic resonance imaging (MRI)-detected lesions not visible on second-look US and analyzed differences in lesion-to-nipple distance between supine and prone positions. Of the 831 consecutive patients who were diagnosed with breast cancer and examined with breast MRI from June 2013 to September 2015, 40 lesions in 37 patients who underwent MR-navigated US for MRI-detected lesions that were not visible on second-look US were included. First, MRI was performed in a prone position using a 1.5-T imager, and second, MRI was performed in a supine position for MR-navigated US. Of 40 lesions, 31 (78%) were identified with MR-navigated US, whereas 5 (13%) lesions disappeared on supine MRI and 4 (10%) exhibited no correlation on MR-navigated US. Of 31 lesions with pathologic confirmation, 7 (23%) were malignant, 2 (6%) were high-risk lesions and 22 (71%) were benign lesions. Comparison of the US findings of benign and malignant lesions revealed that orientation of the lesion differed significantly (p = 0.045), whereas lesion shape, margin and echo pattern did not significantly differ between the two groups (p = 0.088, p = 0.094 and p = 0.412, respectively). Median difference in lesion-to-nipple distance on supine and prone MRI was 8 mm (0-34 mm) in the horizontal direction and 5 mm (0-39.5 mm) in the vertical direction. Thirteen lesions exhibited a >1-cm difference in both horizontal and vertical directions. In conclusion, MR-navigated US was useful for the evaluation of MRI-detected lesions that were not visible on second-look US in breast cancer patients.

A Multicenter Phase II Trial of Neoadjuvant Chemotherapy with Docetaxel and Gemcitabine in Locally Advanced Breast Cancer.

PURPOSE: The current multicenter phase II study was conducted to evaluate the efficacy and safety of the combination of docetaxel and gemcitabine as neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. METHODS: A total of 98 patients with stage II-III breast cancer were enrolled. The primary endpoint was pathological complete response (pCR) rate of invasive cancer after the completion of the fourth cycle of NAC. The secondary endpoints included response rate (RR), rate of breast-conserving surgery, toxicity, and disease-free survival (DFS). This study is registered with ClinicalTrials.gov (NCT01352494). RESULTS: pCR in the breast and the axillary lymph node was observed in seven of the 98 enrolled patients (7.1%). The overall clinical RR, including partial responses, was 65.3%. Breast-conserving surgery was performed in 75 of the 98 assessable patients (76.5%). Neutropenia was frequent and was observed in 92 of the 98 patients (93.9%), including grade 3 and 4 in 24 patients (24.5%) and 63 patients (64.3%), respectively. Dose reductions were required for 30 of the 92 patients (32.6%). After a median follow-up of 24 months, the overall DFS of the group was 86.7%. CONCLUSION: The combination of docetaxel and gemcitabine did not improve pCR. However, this regimen has shown potential as a NAC by producing a reasonable rate of breast-conserving surgery and favorable responses in patients with locally advanced breast cancer. The therapeutic efficacy of this regimen will be determined in additional trials to overcome the limitations of the current study.

Metabolic Activity of Normal Glandular Tissue on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Correlation with Menstrual Cycles and Parenchymal Enhancements.

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.

Young Age Is Associated with Increased Locoregional Recurrence in Node-Positive Breast Cancer with Luminal Subtypes.

PURPOSE: The effects of biological subtypes within breast cancer on prognosis are influenced by age at diagnosis. We investigated the association of young age with locoregional recurrence (LRR) between patients with luminal subtypes versus those with nonluminal subtypes. MATERIALS AND METHODS: Medical records of 524 breast cancer patients with positive lymph nodes between 1999 and 2010 were reviewed retrospectively. All patients received curative surgery and adjuvant chemotherapy based on contemporary guidelines. Radiation was delivered for patients who underwent breast conserving surgery or those who had four or more positive lymph nodes after mastectomy. Adjuvant hormone therapy was administered to 413 patients with positive hormone receptors according to their menstrual status. RESULTS: During median follow-up of 84 months, the 10-year locoregional recurrence-free survival rate (LRRFS) was 84.3% for all patients. Patients < 40 years showed significantly worse 10-year LRRFS than those ≥ 40 years (73.2% vs. 89.0%, respectively; p=0.01). The negative effect of young age on LRRFS was only observed in luminal subtypes (69.7% for < 40 years vs. 90.8% for ≥ 40 years; p < 0.01). Multivariate analysis using luminal subtypes ≥ 40 years as a reference revealed luminal subtypes < 40 years were significantly associated with increased risk of LRR (hazard ratio, 2.33; p < 0.01). CONCLUSION: Young breast cancer patients with positive lymph nodes had a higher risk of LRR than those aged ≥ 40 years. This detrimental effect of young age on LRR was confined in luminal subtypes.

Value of volume-based metabolic parameters for predicting survival in breast cancer patients treated with neoadjuvant chemotherapy.

We evaluated the role of metabolic parameters in the prediction of disease recurrence in operable invasive ductal breast cancer patients treated with neoadjuvant chemotherapy (NAC).We retrospectively evaluated 139 female patients (mean age, 46.5 years; range: 27-72 years) with invasive ductal breast cancer, treated with NAC followed by surgery. All patients underwent F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging at baseline and after completion of NAC before surgery. The prognostic significance of clinicopathological and imaging parameters for disease-free survival (DFS) was evaluated.Recurrence of cancer was detected in 31 of 139 patients (22.3%; follow-up period: 6-82 months). Baseline maximum standardized uptake value, metabolic tumor volume (MTV), and reduction rate (RR) of MTV after NAC were significant independent prognostic factors for DFS in a multivariate analysis (all P < 0.05). The survival functions differed significantly between low and high histological grades (P < 0.001). DFS of the patients with high baseline MTV (≥5.23 cm) was significantly poorer than that of low MTV patients (P = 0.019). The survival function of the group with low RR of MTV after NAC (≤90.72%) was poorer than the higher RR of the MTV group (P = 0.008).Our findings suggest that breast cancer patients who have a high histological grade, large baseline MTV, or a small RR of MTV after NAC should receive great attention to check for possible recurrence.

Comparison of Treatment Outcomes between Breast Conserving Surgery Followed by Radiotherapy and Mastectomy Alone in Patients with T1-2 Stage and 1-3 Axillary Lymph Nodes in the Era of Modern Adjuvant Systemic Treatments.

PURPOSE: The role of postmastectomy radiotherapy in the treatment of T1-2 primary tumor with 1-3 positive lymph nodes is controversial. We compared treatment outcomes between breast conserving surgery followed by radiotherapy (BCS+RT) and total mastectomy alone (TM) in the setting of modern adjuvant systemic treatments. METHODS: Patients with T1-2 primary breast cancer and 1-3 positive lymph nodes who were treated between 2001 and 2011 were divided into 2 groups based on the treatment approach: BCS+RT (n = 169) and TM (n = 117). All patients received adjuvant chemotherapy including taxanes. Adjuvant endocrine therapy was administered to patients with positive hormone receptors according to their menstrual status. RESULTS: During a median follow-up of 76.5 months, 21 patients (7.3%) experienced locoregional recurrence as the first event, including 7 patients (4.1%) in the BCS+RT group and 14 patients (12.0%) in the TM group. The 5-year cumulative incidence rate of locoregional recurrence was 2.5% for BCS+RT versus 9.5% for TM (p = 0.016). Competing risk regression analysis revealed that TM was associated with a relative risk for locoregional recurrence of 5.347 (p = 0.003). TM was also associated with a significantly lower 5-year disease-free survival rate compared with BCS+RT (hazard ratio, 2.024; 95% confidence interval, 1.090-3.759; p = 0.026). CONCLUSION: To improve treatment outcomes for TM even after modern systemic treatments, postmastectomy radiotherapy might be required for patients with T1-2 primary breast cancer and 1-3 positive lymph nodes.

c-myc amplification is associated with HER2 amplification and closely linked with cell proliferation in tissue microarray of nonselected breast cancers.

C-myc and HER2 amplification were analyzed on 214 consecutive breast cancers by fluorescence in situ hybridization using tissue microarray technology. The frequencies of amplification were 15.4% (33/214) and 23.3% (49/210), respectively. c- myc amplification was significantly associated with HER2 amplification ( P < .001) and closely linked with cell proliferative activity, measured by Ki67 labeling index ( P = .010). In univariate survival analysis, lymph node status, tumor size, and histological grade were significant prognostic factors, but in multivariate analysis, lymph node status was the only significant factor. Patient survival did not differ according to c- myc amplification status, and c- myc amplification showed no significant correlation with clinicopathologic features of the tumors. A strong correlation between c- myc and HER2 amplification and proliferative activity indicates a biological link between these genes in breast cancer cell.

Tumor metabolism and perfusion ratio assessed by 18F-FDG PET/CT and DCE-MRI in breast cancer patients: Correlation with tumor subtype and histologic prognostic factors.

OBJECTIVE: Our purpose was to evaluate whether breast cancer with high metabolic-perfusion ratio would be associated with poor histopathologic prognostic factors and whether triple negative breast cancer (TNBC) would show high metabolic-perfusion ratio compared to non-triple negative breast cancer (non-TNBC). METHODS: From March 2011 to November 2011, 67 females with invasive ductal carcinoma of breast who underwent both MRI and 18F-FDG PET/CT were included. Perfusion parameters including Ktrans, Kep and Ve were acquired from Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Metabolic parameters including the standardized uptake value (SUV) and volumetric metabolic parameters including metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). RESULTS: In non-TNBC, SUVmax was significantly correlated with Kep (ρ=0.298, p=0.036) and Ve (ρ=-0.286, p=0.044). In TNBC, there was no significant correlation between all perfusion and metabolic parameters. Compared to non-TNBC, higher SUVmax (10.2 vs 5.3, p<0.001), higher SUVmax/Ktrans (56.02 vs 20.3, p<0.001), higher MTV50/Ktrans (7.8 vs 16.54, p<0.001), higher TLG50/Ktrans (36.49 vs 12.3, p<0.001), higher TLG50/Ve (91.34 vs 27.1 p=0.022) were significantly correlated with TNBC. Lower Ktrans (0.17 vs 0.29, p=0.017) and lower Ve (0.29 vs 0.41, p=0.011) were also significantly associated TNBC. CONCLUSION: While several perfusion parameters and metabolic parameters were correlated in non-TNBC, they were not correlated in TNBC. TNBC showed higher metabolic-perfusion ratios compared to non-TNBC.

Histologic Grade and Decrease in Tumor Dimensions Affect Axillary Lymph Node Status after Neoadjuvant Chemotherapy in Breast Cancer Patients.

PURPOSE: The purposes our study was to find out any histologic factors associated with negative conversion of axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC). We also evaluated the association between the decrease in size of primary breast tumor and negative conversion of ALN. METHODS: From January 2012 to November 2014, we included 133 breast cancer patients who underwent NAC and who had ALN metastases which were confirmed on fine-needle aspiration or core needle biopsy at initial diagnosis. All 133 patients underwent initial magnetic resonance imaging (MRI) at the time of diagnosis and preoperative MRI after completion of NAC. We measured the longest dimension of primary breast cancer on MRI. RESULTS: Of 133 patients, 39 patients (29%) showed negative conversion of ALN and of these 39 patients, 25 patients (64%) showed pathologic complete remission of primary breast. On univariate analysis, mean percent decrease in longest dimension, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status and histologic grade were significantly associated with the ALN status after NAC (p<0.001, p=0.001, p< 0.001, p=0.001, p=0.002, respectively). On multivariate logistic regression analysis, percent decrease in longest dimension (odds ratio, 1.026; 95% confidence interval [CI], 1.009-1.044) and histologic grade (odds ratio, 3.964; 95% CI, 1.151-13.657) were identified as being independently associated with the ALN status after NAC. The area under the receiver operating characteristic curve was 0.835 with the best cutoff value of 80% decrease in longest dimension. Combination of high histologic grade and more than 80% decrease in longest dimension showed 64% sensitivity and 92% specificity. CONCLUSION: High histologic grade and more than 80% decrease in primary tumor dimension were associated with negative conversion of ALN after NAC.

Sentinel lymph node biopsy alone after neoadjuvant chemotherapy in patients with initial cytology-proven axillary node metastasis.

PURPOSE: Neoadjuvant chemotherapy (NAC) has been recently used to downstage breast cancer. However, in patients with initial axillary lymph node (ALN) metastasis, ALN dissection regardless of the NAC response remains the standard treatment. The purpose of this study was to identify the feasibility and accuracy of sentinel lymph node biopsy (SLNB) after NAC in patients with ALN metastasis at diagnosis. METHODS: From January 2007 to August 2013, data of patients who were diagnosed with invasive breast cancer and ALN metastasis and treated with NAC followed by definitive surgery in two centers were collected retrospectively. A total of 386 patients were enrolled and classified into five groups according to surgical procedure for the ALNs and pathologic results. RESULTS: At SLNB after NAC, sentinel lymph nodes (SLNs) that stained blue or were hot, including suspicious nodes, were identified; the SLN identification and false-negative rates was 96% and 10%, respectively. There was no difference in the overall survival among the groups. For patients who revealed a pathologic complete node response, there was a significant difference in the disease-free survival rate between the SLNB only and complete ALN dissection groups (p=0.031). However, the rate of axillary recurrence demonstrated no significant differences among the groups (p>0.050). CONCLUSION: SLNB after NAC in breast cancer patients with initial ALN metastasis may help identify downstaging to negative nodal status and thereby reduce the surgical morbidity by avoiding standard ALN dissection.

Cyclin D1 expression and patient outcome after tamoxifen therapy in estrogen receptor positive metastatic breast cancer.

Cyclin D1 expression is closely related with ER status in breast cancer. We executed this study to evaluate whether therapeutic response to tamoxifen varies with levels of cyclin D1 expression in 66 ER positive breast cancer patients having solitary bone metastasis. Treatment response to tamoxifen and correlation between cyclin D1 expression and biologic data of the patients were analyzed. Cyclin D1 expression was detected in 46 patients (69.7%) and significantly reduced in poorly differentiated cancer (p=0.023). Patients with cyclin D1-expressing tumors showed better response to tamoxifen but the difference was not statistically significant. Cyclin D1 expression was associated with differentiation of the breast cancer but not useful in discriminating a good responder to tamoxifen treatment.

Analysis of the potent prognostic factors in luminal-type breast cancer.

PURPOSE: Luminal-type breast cancer has a good prognosis compared to other types, such as human epidermal growth factor receptor 2 and triple negative types. Luminal-type breast cancer is classified into luminal A and B, according to the proliferation index. We investigated the clinicopathological factors that affect the prognosis of the luminal-type subgroups. METHODS: We reviewed the medical records and the pathologic reports of 159 luminal-type breast cancer patients who were treated between February 2005 and November 2007. We divided luminal-type breast cancer into luminal A and B, according to Ki-67 (cutoff value, 14%) and analyzed the clinicopathologic factors, such as age at diagnosis, intensity score of estrogen receptor and progesterone receptor, histologic grade, and Bcl-2. Moreover, we compared the disease-free survival (DFS) of each group. RESULTS: In the univariate analysis, age (p=0.004), tumor size (p=0.010), lymph node metastasis (p=0.001), and Bcl-2 (p=0.002) were statistically significant factors in luminal-type breast cancer. In the multivariate analysis, lymph node (p=0.049) and Bcl-2 (p=0.034) were significant relevant factors in luminal-type breast cancer. In the subgroup analysis, the increased Bcl-2 (cutoff value, 33%) was related with a longer DFS in the luminal B group (p=0.004). CONCLUSION: In our study, luminal A breast cancer showed a longer DFS than luminal B breast cancer, further, Bcl-2 may be a potent prognostic factor in luminal-type breast cancer.

Comparative study of a single-incision laparoscopic and a conventional laparoscopic appendectomy for the treatment of acute appendicitis.

PURPOSE: For the treatment of acute appendicitis, a conventional laparoscopic appendectomy (LA) has been widely performed. Recently, the use of single incision laparoscopic surgery (SILS) is increasing because it is believed to have advantages over conventional laparoscopic surgery. In this study, we compared SILS and a conventional LA. METHODS: We analyzed the 217 patients who received laparoscopy-assisted appendectomies between August 2010 and April 2012 at Inje University Sanggye Paik Hospital. One hundred-twelve patients underwent SILS, and 105 patients underwent LA. For the two groups, we compared the operation times, postoperative laboratory results, postoperative pain, hospital stay, and postoperative complications. RESULTS: The patients' demographics, including body mass index, were not significantly different between the two groups. There were 6 perforated appendicitis cases in the SILS group and 5 cases in the LA group. The mean operative time in the SILS group was 65.88 ± 22.74 minutes whereas that in the LA group was 61.70 ± 22.27 minutes (P = 0.276). There were no significant differences in the mean hospital stays, use of nonsteroidal antiinflammatory drugs, and wound infections between the two groups. CONCLUSION: Postoperative pain, complications and hospital stay showed no statistically significant differences between the SILS and the LA groups. However, our SILS method uses a single trocar and two latex tubes, so cost savings and reduced interference during surgery are expected.