Erratum: Validation of a Web-Based Tool to Predict the Ipsilateral Breast Tumor Recurrence (IBTR! 2.0) after Breast-Conserving Therapy for Korean Patients.

[This corrects the article on p. 97 in vol. 16, PMID: 23593089.].

Limited Supraclavicular Radiation Field in Breast Cancer With ≥ 10 Positive Axillary Lymph Nodes.

PURPOSE: The present study was conducted to evaluate the patterns of recurrence and factors related to axillary or supraclavicular recurrence (ASR) and to suggest the probable indications of supraclavicular radiotherapy (SCRT) field modification for breast cancer patients with ≥ 10 axillary lymph node (LN) metastases who had received the current standard systemic management and limited-field SCRT. MATERIALS AND METHODS: We performed a retrospective study of patients with breast cancer with ≥ 10 axillary LN metastases who had received standard surgery with postoperative RT, including limited SCRT (level III and supraclavicular area) and taxane-based adjuvant chemotherapy (except for neoadjuvant chemotherapy), from January 2000 to June 2012. ASR was defined as recurrence to levels I to III of the axillary or supraclavicular area. RESULTS: The present study included 301 patients with breast cancer with ≥ 10 axillary LN metastases. The median follow-up period was 59.1 months (range, 7.4-167.9 months). Overall, 32 cases (10.6%) of locoregional recurrence were observed, and 27 patients (9.0%) exhibited ASR. Additionally, 16 patients (5.3%) developed recurrence in levels I or II of the axillary area, which are not included in the SCRT field. ASR-free survival was significantly related to the LN ratio (LNR) in both univariate and multivariate analysis. CONCLUSION: ASR was the most prevalent locoregional recurrence pattern in patients with breast cancer with ≥ 10 axillary LN metastases, and LNR was a significant prognostic factor for the development of ASR. Modification of the SCRT field, including the full axilla, should be considered in patients with a greater LNR.

Comparison of Clinicopathological Features and Treatment Results between Invasive Lobular Carcinoma and Ductal Carcinoma of the Breast.

PURPOSE: The purpose of this study was to assess the incidence of invasive lobular carcinoma (ILC) and to compare the clinicopathological features and treatment results after breast conserving surgery (BCS) followed by radiotherapy between ILC and invasive ductal carcinoma (IDC). METHODS: A total of 1,071 patients who underwent BCS followed by radiotherapy were included in the study. Medical records and pathological reports were retrospectively reviewed. RESULTS: The incidence of ILC was 5.2% (n=56). Bilateral breast cancer, lower nuclear grade, and hormone receptor-positive breast cancer were more frequent in patients with ILC than in those with IDC. There were no cases of lymphovascular invasion or the basal-like subtype in patients with ILC. There were no statistically significant differences in patterns of failure or treatment outcomes between patients with ILC and those with IDC. The development of metachronous contralateral breast cancer was more frequent in patients with IDC (n=27). Only one patient with ILC developed contralateral breast cancer, with a case of ductal carcinoma in situ. CONCLUSION: The incidence of ILC was slightly higher in our study than in previous Korean studies, but was lower than the incidences reported in Western studies. The differences we observed in clinico pathological features between ILC and IDC were similar to those described elsewhere in the literature. Although there were no statistically significant differences, there was a trend toward better disease-specific survival and disease-free survival rates in patients with ILC than in those with IDC.

Distinguishing Low-Risk Luminal A Breast Cancer Subtypes with Ki-67 and p53 Is More Predictive of Long-Term Survival.

Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.

Clinical Outcomes and Prognostic Factors of Pathologic N3 Breast Cancer Treated With Modern Standard Treatments.

BACKGROUND: The aim of the present study was to investigate clinical outcomes and identify prognostic factors in pathologic N3 (pN3) breast cancer patients who received the current standard management. PATIENTS AND METHODS: We performed a retrospective study with 333 pN3 breast cancer patients who received curative surgery with postoperative radiation therapy and taxane-based adjuvant chemotherapy from January 2000 to June 2012. The median follow-up period was 58.3 months (range, 7.4-167.9 months). All of the 243 patients who were hormone receptor-positive received endocrine therapy, and trastuzumab therapy was used in 63 of 88 (71.6%) HER2-positive patients. RESULTS: Overall, 112 disease recurrences (33.6%) were documented during the follow-up. The first site of recurrence was locoregional in 21 patients (6.3%), distant metastases in 72 patients (21.6%), and both in 19 patients (5.7%). The disease-free survival (DFS) and overall survival were 63.3% and 86.9% at 5 years, respectively. DFS was significantly related to age (> 40 years; P = .008; hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.40-0.87), nuclear grade (I or II; P = .02; HR, 0.64; 95% CI, 0.44-0.93), and positive lymph node ratio (≤ 60%; P = .004; HR, 0.56; 95% CI, 0.38-0.83) in multivariate analysis. HER2-positive patients who were treated with trastuzumab showed more favorable DFS than HER2-negative patients. CONCLUSION: More than 60% of the pN3 breast cancer patients treated with the current standard management lived without disease longer than 5 years. Age, nuclear grade, and lymph node ratio were significant prognostic factors in pN3 breast cancer patients.

Prognostic Modeling in Pathologic N1 Breast Cancer Without Elective Nodal Irradiation After Current Standard Systemic Management.

OBJECTIVE: This study was conducted to establish a prognostic model in patients with pathologic N1 (pN1) breast cancer who have not undergone elective nodal irradiation (ENI) under the current standard management and to suggest possible indications for ENI. METHODS: We performed a retrospective study with patients with pN1 breast cancer who received the standard local and preferred adjuvant chemotherapy treatment without neoadjuvant chemotherapy and ENI from January 2005 to June 2011. Most of the indicated patients received endocrine and trastuzumab therapy. RESULTS: In 735 enrolled patients, the median follow-up period was 58.4 months (range, 7.2-111.3 months). Overall, 55 recurrences (7.4%) developed, and locoregional recurrence was present in 27 patients (3.8%). Recurrence-free survival was significantly related to lymphovascular invasion (P = .04, hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.03-2.88), histologic grade (P = .03, HR, 2.57; 95% CI, 1.05-6.26), and nonluminal A subtype (P = .02, HR, 3.04; 95% CI, 1.23-7.49) in multivariate analysis. The prognostic model was established by these 3 prognostic factors. Recurrence-free survival was less than 90% at 5 years in cases with 2 or 3 factors. CONCLUSIONS: The prognostic model has stratified risk groups in pN1 breast cancer without ENI. Patients with 2 or more factors should be considered for ENI.

Molecular characterization of patients with pathologic complete response or early failure after neoadjuvant chemotherapy for locally advanced breast cancer using next generation sequencing and nCounter assay.

Neoadjuvant chemotherapy (NAC) has the added advantage of increasing breast conservation rates with equivalent survival outcomes compared with adjuvant chemotherapy. A subset of breast cancer patients who received NAC experienced early failure (EF) during the course of therapy or within a short period after curative breast surgery. In contrast, patients with pathological complete response (pCR) were reported to have markedly favorable outcomes. This study was performed to identify actionable mutation(s) and to explain refractoriness and responsiveness to NAC. Included in this analysis were 76 patients among 397 with locally advanced breast cancer for whom a preoperative fresh-frozen paraffin-embedded tumor block was available for next-generation sequencing using AmpliSeq. The incidence of missense mutations in KRAS was much higher in patients with EF than in other groups (p < 0.01). In contrast, polymorphisms of the cMET gene were found in patients with pCR exclusively (p < 0.01).

Surgery of primary tumour has survival benefit in metastatic breast cancer with single-organ metastasis, especially bone.

BACKGROUND: Surgery for the primary breast tumour is usually not recommended in metastatic breast cancer (MBC); however, some reports have suggested a benefit of locoregional treatment. We designed this study to evaluate the efficacy of locoregional surgery in MBC. METHODS: Data for patients diagnosed with MBC at Samsung Medical Center between 1995 and 2011 were retrospectively collected. We compared the survival benefit of all treatment modalities using Cox regression analysis. Subgroup analyses based on number of metastases were performed to delineate the indication for each treatment. RESULTS: Among 262 patients, 40 (15.3%) underwent surgery. Other treatments included chemotherapy (n = 213, 81.3%), radiotherapy (n = 138, 52.7%), hormone therapy (n = 118, 45.0%) and HER2/neu receptor (HER2)-targeted therapy (n = 37, 14.1%). Cox regression analysis showed that surgery (hazard ratios (HR) = 0.51, P < 0.01), hormone therapy (HR = 0.31, P < 0.01) and HER2-targeted therapy (HR = 0.33, P < 0.01) were associated with improved survival, whereas presence of three or more metastatic organs (HR = 1.62, P = 0.03) was associated with poor survival. In patients with metastasis to a single organ, surgery (HR = 0.43, P < 0.01), chemotherapy (HR = 0.62, P = 0.05), hormone therapy (HR = 0.39, P < 0.01) and HER2-targeted therapy (HR = 0.39, P = 0.02) had a survival benefit. Furthermore, for patients with bone-only metastasis, surgery (HR = 0.37, P = 0.02), chemotherapy (HR = 0.42, P < 0.01), hormone therapy (HR = 0.22, P < 0.01) and HER2-targeted therapy (HR = 0.09, P = 0.02) showed a survival benefit. However, only hormone therapy and HER2-targeted therapy had a survival benefit in MBC with metastasis to multiple organs. CONCLUSION: Surgical control of the primary breast tumour should be considered as a locoregional therapy in combination with systemic therapy in MBC with metastasis to a single organ, especially bone-only metastasis.

Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer.

BACKGROUND: Response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PR) status. Generally, hormone receptor-positive (HR+) breast cancers have favorable prognosis. In order to understand the exact clinical characteristics and prognosis of single HR-positive breast cancer (ER + PR- tumors and ER-PR+ tumors), we compared these tumors to double HR+ tumors as well as HR- negative tumors (ER-PR-). METHODS: We examined the clinical and biological features of 6,980 women with invasive ductal carcinoma, and these patients were stratified according to ER and PR expression as double HR+ (ER + PR+), single HR+ (ER + PR- and ER-PR+) and double HR-negative (HR-, ER-PR-) tumors. RESULTS: In this study, 571 (8.2%) cases were single HR+ tumors, of which 90 (1.3%) were ER-PR+ tumors and 481 (6.9%) were ER + PR- tumors. Our multivariate analysis showed that in patients without HER2 overexpression ER + PR- tumors were associated with an increased risk of recurrence and death compared with ER + PR+ tumors, with a hazard ratio of 2.12 for disease-free survival (DFS) and 4.79 for overall survival (OS). In patients without HER2 overexpression ER-PR+ tumors had increased risk of recurrence and death compared with ER + PR+ tumor, with a hazard ratio of 4.19 for DFS and 7.22 for OS. In contrast, in patients with HER2 overexpression, the difference in survival between single HR+ tumors and double HR+ HR- tumors was not statistically significant. In patients without HER2 overexpression the DFS and OS of ER + PR- and ER-PR+ tumors were not significantly different from those of ER-PR- tumors. CONCLUSION: We have identified clinically and biologically distinct features of single HR+ tumors (ER-PR+ and ER + PR-) through comparison with both ER + PR+ and ER-PR- tumors. These differences were only significant in HER2- tumors, not in HER2+ tumors. Single HR+ tumors without HER2 overexpression (ER + PR-HER2- or ER-PR + HER2-) were associated with poorer survival than ER + PR + HER2- tumors, and had comparable poor survival to ER-PR-HER2- tumors (triple-negative breast cancer).

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.

Proportion and clinical outcomes of postoperative radiotherapy omission after breast-conserving surgery in women with breast cancer.

PURPOSE: The present study was conducted to investigate the proportion and clinical outcomes of breast cancer patients who did not receive postoperative radiotherapy (PORT) after breast-conserving surgery (BCS). METHODS: This retrospective study included all breast cancer patients received curative BCS without PORT between 2003 and 2013. In the PORT omission group, characteristics and local recurrence differences were compared between the recommended group and the refused group. To compare the local recurrence-free survival (LRFS) of the PORT omission group and the control group who received PORT, subjects were selected by using the pooled data of patients treated between 1994 and 2007. RESULTS: During the study period, 96 patients did not receive PORT among a total of 6,680 patients who underwent BCS. Therefore, the overall rate of PORT omission was 1.4%. Among the 96 patients, 20 were recommended for PORT omission (recommended group) and 76 refused PORT (refused group). The median follow-up period of all study participants was 19.3 months (range, 0.3-115.1 months). Patients in the recommended group were older (p=0.004), were more likely to be postmenopausal (p=0.013), and had more number of positive prognostic factors compared with the refused group. Overall, 12 cases of disease recurrence, including 11 cases of local recurrence, developed in the PORT-refused group. The LRFS of the PORT-omission group was significantly inferior to that of patients who received PORT after BCS (p<0.001). In the PORT-omission group, significant favorable prognostic factors for LRFS were having histologic grade 1 or 2 disease (p=0.023), having no axillary lymph node metastasis (p=0.039), receiving adjuvant endocrine therapy (p=0.046), and being in the recommended group (p=0.026). CONCLUSION: The rate of PORT omission in the present study is very low among women who underwent surgery compared to that of other studies worldwide. PORT omission is significantly related to a high local recurrence rate.

Retraction note to: "Clinical Significance of the Axillary Arch in Sentinel Lymph Node Biopsy".

[This retracts the article on p. 244 in vol. 17, PMID: 25320622.].

Prevalence and clinical outcomes of young breast cancer (YBC) patients according to intrinsic breast cancer subtypes: Single institutional experience in Korea.

The purpose of our study was to investigate and identify comprehensively the clinicopathological features and long-term outcome of young breast cancer (YBC) according to intrinsic subtype. We analyzed clinical and pathological characteristics of 2844 women who were diagnosed with invasive breast cancer from 2000 to 2007 and the treatment outcomes by age at diagnosis. The median age of the patients was 46 years (range, 21-83 years), and we divided them into three age group: ≤35 years (Group 1), 36-50 years (Group 2), and >50 years (Group 3). During a median follow-up of 100 months, the 5-year recurrence-free survival rate (RFSR) and overall survival rate (OSR) were 90.8% and 94.6%, respectively. The 10-year estimated RFSR and OSR were 81.9% and 86.9%, respectively. The prognosis of TN subtype appeared not to be worse than that of other subtypes in Group 1. In Group 1 alone (≤35 years), subtype was not identified as an independent risk factor for distant recurrence-free survival (DRFS) in a Cox-regression multivariate model (hazard ratio, 0.85; 95% CI, 0.68-1.06; p = 0.148). This analysis revealed a very high prevalence of YBC in this cohort. The poor outcomes of YBC patients might result from an increased frequency of triple negative (TN)/HER2 subtypes and the more aggressive clinical behavior of ER-positive tumors compared with older patients. Further research to elucidate the biologic difference of the ER+ tumors of YBC patients is warranted.

Immediate postoperative inflammation is an important prognostic factor in breast cancer.

OBJECTIVE: Inflammation is associated with worse outcomes in cancer. Operations induce an acute inflammatory response and could impact the clinical outcomes in breast cancer. The neutrophil-lymphocyte ratio (NLR) is a well-known indicator of inflammation. We investigated the prognostic significance of perioperative inflammation with the NLR in breast cancer. METHODS: We reviewed the clinical and pathological records of women diagnosed with invasive breast carcinoma at the Samsung Medical Center between 2000 and 2010. The NLR levels in the immediate preoperative period and the postoperative periods (1 week and 1 month) were assessed. RESULTS: The NLRs of a total of 3,116 breast cancer patients were examined. In the univariate analysis, the NLR in postoperative week 1, total mastectomy, the presence of lymphovascular invasion, a higher nuclear grade and pathologic TNM stage, and negative hormone receptor and subtypes were factors associated with poor disease-specific survival. The NLR in postoperative week 1 remained a significant prognostic factor in the multivariate analysis. A cutoff level of 5.2, determined by the minimum p value approach, was found to be a significant level for discriminating the impact on breast cancer-specific mortality (p = 0.0116 adjusted by the Bonferroni correction). CONCLUSIONS: Immediate postoperative inflammation is an important prognostic marker in breast cancer patients.

Lateral neck sentinel lymph node biopsy in papillary thyroid carcinoma, is it really necessary? A randomized, controlled study.

BACKGROUND: Although occult metastasis to lymph node in the lateral neck compartment is common in papillary thyroid carcinoma (PTC), the clinical impact of these metastasis is unknown. We hypothesized that sentinel lymph node biopsy (SLNB) of the lateral neck compartment with radioisotopes may detect occult metastasis, which could prevent recurrence. METHODS: This randomized, controlled study was conducted from June 2009 to January 2011 and included 283 patients with PTC who were receiving treatment at the Samsung Medical Center. RESULTS: Of the 283 patients enrolled in the study, 141 were randomized to a lateral SLNB (LSLNB) group and 142 patients were to the control group. Lateral sentinel lymph nodes (LSLNs) were identified in 80 of the 127 patients (63.0%) for whom stimulated thyroglobulin (sTg) levels were available. Among the 80 patients with LSLNs, 24 (30.0%) had metastases and underwent an ipsilateral modified radical neck dissection. Among the 191 patients for whom repeated sTg test results were available, the first median level of sTg in the LSLNB study group was less compared with the control group (P = .012, adjusted for duration). However, the second sTg level (after the first radioactive iodine ablation) was not different between the 2 groups. Moreover, the sTg levels were not significantly different between the LSLN-positive (n = 23) and other patients (n = 168) after the first and second ablations. During patient follow-up (median, 39 months; range, 7-55), 3 cases of recurrence were observed in the control group and 1 case in the study group (a LSLN had not been detected in this case). CONCLUSION: Although LSLNB was able to remove occult metastasis in PTC, this procedure had no effect on either sTg levels or on recurrence rates at a mean follow-up of 39 months. Additional long-term studies are needed to explore fully the clinical usefulness of LSLNB in the prevention of PTC recurrence.

Prognostic relevance of biological subtype overrides that of TNM staging in breast cancer: discordance between stage and biology.

Recently, we faced difficult treatment decisions regarding appropriate adjuvant systemic treatment, especially for patients who show discordance between stage and tumor biology. The aim of this study was to compare the prognostic relevance of the TNM staging system with that of intrinsic subtype in breast cancer. We retrospectively identified women patients who received curative surgery for stage I-III breast cancer with available data on immunohistochemistry profiles including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, and Ki 67 staining at the Samsung Medical Center from January 2004 to September 2008. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). A total of 1145 patients were diagnosed with breast cancer and received curative surgery. Of these, 463 (40.4%) patients were stage I, and 682 (59.6%) were stage II or III. In addition, 701 (61.2%) patients were HR positive, 239 (20.9%) were HER2 positive, and 205 (20.9%) had triple-negative breast cancer. The 5-year RFS for the patients who were HR positive and HER2 negative with a low Ki 67 staining score (0-25%) was 99%. The 5-year RFS for patients who were HER2-positive or had triple-negative breast cancer were 89 and 83%, respectively (P value = <0.001). In multivariate analysis, advanced stage (II/III) and unfavorable biology (HER2 positive or triple negative) retained their statistical significance as predictors of decreased RFS and OS. Patients with advanced-stage disease (II or III) but favorable tumor biology (HR positive and HER2 negative and low Ki 67) had better clinical outcomes than those with stage I disease and unfavorable tumor biology in terms of RFS (99 versus 92%, P value = 0.011) and OS (99 versus 96%, P value = 0.03) at 5 years. The current results showed that intrinsic subtype has a greater prognostic impact in predicting clinical outcomes in subpopulations of patients with stage I-III breast cancer who show discordance between stage and biologic subtypes.

Volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence in breast cancer.

PURPOSE: To evaluate the prognostic value of a volume-based metabolic tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIALS AND METHODS: This study was approved by the institutional review board, with waivers of informed consent. One hundred sixty-seven patients (mean age, 44 years; range, 22-68 years) with clinical stage II or III breast cancer who underwent fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography scans at baseline and after completion of neoadjuvant chemotherapy between July 2006 and June 2013 were selected. The association between the metabolic response parameters and the disease-free survival was assessed by using a Cox proportional hazards regression model and time-dependent receiver operating characteristic curve analysis. Metabolic response parameters included the maximum standardized uptake value (SUVmax), the total metabolic tumor volume (MTVtotal), and the relative decrease in SUVmax and MTVtotal. RESULTS: In the Cox model, posttreatment SUVmax (P = .029) and MTVtotal (P = .028) and relative decreases in SUVmax (P = .032) and MTVtotal (P = .005) after neoadjuvant chemotherapy were significantly associated with disease-free survival after adjusting for pretreatment clinical stage, yp stage, and tumor subtype. In the time-dependent receiver operating characteristic curve analysis, MTVtotal after neoadjuvant chemotherapy had the highest association with outcome compared with the other parameters (P < .001). MTVtotal of up to 0.2 cm(3) after neoadjuvant chemotherapy was significantly associated with a favorable outcome in patients who did not achieve pathologic complete response after neoadjuvant chemotherapy. CONCLUSION: The volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence, regardless of tumor subtype and pathologic tumor response.

A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers who receive adjuvant chemotherapy following surgery.

The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate triple negative breast cancers (TNBCs) among patients, who received adjuvant chemotherapy after curative surgery. We tested whether the results of a NanoString expression assay that targeted 250 prospectively selected genes and used mRNA extracted from formalin-fixed, paraffin-embedded would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high). NanoString expression profiles were obtained for 203 tumor tissue blocks. Increased expressions of the five genes (SMAD2, HRAS, KRT6A, TP63 and ETV6) and decreased expression of the two genes (NFKB1 and MDM4) were associated favorable prognosis and were validated with cross-validation. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low- and high-risk groups according to gene expression signature were 62% [95% confidence interval (CI), 48.6-78.9%] and 85% (95% CI, 79.2-90.7%), respectively. When adjusting for TNM stage, the distant recurrence-free survival (DRFS)s in the low-risk group was significantly longer than that in the high-risk group (p <0.001) for early stage (I and II) and advanced stage (III) tumors. In a multivariate Cox regression model, the gene expression signature provided significant predictive power jointly with the TNM staging system. A seven-gene signature could be used as a prognostic model to predict DRFS in patients with TNBC who received curative surgery followed by adjuvant chemotherapy.

Incidental Findings on Simulation CT Images for Adjuvant Radiotherapy in Breast Cancer Patients.

We designed this study to evaluate the incidence of incidental findings on computed tomography (CT) scan implemented as simulation for adjuvant radiotherapy in breast cancer patients and to emphasize the need for careful review of simulation CT images before planning radiotherapy. A Resident and attending radiation oncologists retrospectively reviewed the medical records and simulation CT images of 776 patients treated with adjuvant radiotherapy at Samsung Medical Center during 2008. Previously undetected abnormal findings on simulation CT images were defined as incidental findings and interpreted by diagnostic radiologist. If the incidental findings required further evaluation or follow-up, they were defined as indeterminate findings. If subsequent cancers were diagnosed according incidental findings, they were defined as malignancy-related findings. There were 81 indeterminate findings (10.8%) including thyroid nodule, solitary pulmonary nodule, mediastinal lymph node, supraclavicular or axillary lymph node. Among them, there were nine malignancy-related findings (1.3%), including four thyroid cancers, three lung metastases, one primary lung cancer, and one axillary lymph node recurrence. The incidence of incidental findings in this study was low, but some of the findings were related to malignancy. Radiation oncologists should be alert to incidental findings on simulation CT, and incidental findings should be evaluated by diagnostic radiologists.

Anticancer effect of silibinin on the xenograft model using MDA-MB-468 breast cancer cells.

PURPOSE: The aim of this study is to know whether silibinin has an anticancer effect on triple negative breast cancer xenograft model using MDA-MB-468 cells. METHODS: To establish the xenograft model, we injected the MDA-MB-468 cells into female Balb/c-nude mice. After establishing a xenograft model, oral silibinin was administered to the tested mice in the way of 200 mg/kg for 45 days. The difference of mean tumor volume between silibinin fed mice and control mice was analyzed. The epidermal growth factor receptor (EGFR) phosphorylation in MDA-MB-468 cells was analyzed by Western blotting. The expression of VEGF, COX-2, and MMP-9 genes in tumor tissue was analyzed by real-time polymerase chain reaction (PCR). RESULTS: In the xenograft model using MDA-MB-468 cells, we found that oral administration of silibinin significantly suppressed the tumor volume (silibinin treated mice vs. control mice; 230.3 ± 61.6 mm(3) vs. 435.7 ± 93.5 mm(3), P < 0.001). The phosphorylation of EGFR in MDA-MB-468 cells was inhibited by treatment with 50 µg/mL of silibinin. In real time-PCR analysis of tumor tissue obtained from sacrificed mice, the gene expression of MMP-9, VEGF, and COX-2 was 51.8%-80% smaller in silibinin group than that of control group and we can also verify the similar result using Western blotting analysis. CONCLUSION: We verified that silibinin had anticancer effect on xenograft model of MDA-MB-468 cells in the way of preventing the phosphorylation of EGFR and eventually suppressed the production of COX-2, VEGF, and MMP-9 expression. Finally, the tumor volume of xenograft models was decreased after administration of Silibinin.