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.

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.

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.

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.

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).

The protective effect of parity in hormone receptor-positive, Ki-67 expressing breast cancer.

BACKGROUND: Epidemiologic studies showed that the experience of pregnancy is associated with a reduced risk of breast cancer. We hypothesized that parity may differentially be associated with the development of invasive breast cancer by each subtype. METHODS: We reviewed the clinical, radiological, and pathological records of women diagnosed with invasive ductal carcinoma of the breast at Samsung Medical Center between 2005 and 2009. Clinicopathologic results were assessed by χ(2) and Fisher's exact tests with a Bonferroni correction for categorical variables, and by the Kruskal-Wallis test for nonparametric continuous variables. A multinomial logistic regression model was used for multivariate analysis. RESULTS: Among a total of 3,095 patients, 283 (9.14 %) patients were nulliparous. Older age, higher pN, and expression of HER2 were associated with parity. In the analysis between parity and molecular subtypes, parity also had a variable influence on breast cancer subtypes (p = 0.032). Intergroup analysis with multiple comparison showed that luminal B subtype was related to nulliparity compared with HER2-positive subtypes (p = 0.03). CONCLUSIONS: The effect of parity on the development of breast cancer differed by hormone receptor and HER2 expression. It seems that parity might have a protective effect against hormone receptor-positive breast cancer, especially cancers expressing HR+ and Ki-67. Further basic research to define and understand this result is ongoing.

Zerumbone suppresses IL-1ß-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells.

Inflammation is a key regulatory process in cancer development. Prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transition, which is the principal mechanism involved in metastasis and tumor invasion. Interleukin (IL)-1ß is a major inflammatory cytokine in a variety of tumors. To date, the regulatory mechanism of IL-1ß-induced cell migration and invasion has not been fully elucidated. Here, we investigated the effect of zerumbone (ZER) on IL-1ß-induced cell migration and invasion in breast cancer cells. The levels of IL-8 and matrix metalloproteinase (MMP)-3 mRNA were analyzed by real-time polymerase chain reaction. The levels of secreted IL-8 and MMP-3 protein were analyzed by enzyme-linked immunosorbent assay and western blot analysis, respectively. Cell invasion and migration was detected by Boyden chamber assay. The levels of IL-8 and MMP-3 expression were significantly increased by IL-1ß treatment in Hs578T and MDA-MB231 cells. On the other hand, IL-1ß-induced IL-8 and MMP-3 expression was decreased by ZER. Finally, IL-1ß-induced cell migration and invasion were decreased by ZER in Hs578T and MDA-MB231 cells. ZER suppresses IL-1ß-induced cell migration and invasion by inhibiting IL-8 expression and MMP-3 expression in TNBC cells. ZER could be a promising therapeutic drug for treatment of triple-negative breast cancer patients.

HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients.

Breast cancer is a highly heterogeneous malignancy. The triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer subtypes are highly aggressive and are associated with a poor prognosis. The therapeutic targets for TNBC remain undefined, and many patients with the HER2 subtype acquire resistance to therapy after prolonged treatment. The objective of this study was to evaluate the prognostic significance of HER3 expression in invasive breast carcinoma. We established matched tissue microarray (TMA) blocks and clinical data from 950 cases of invasive breast carcinoma with long-term clinical follow-up data (median 109.7 months). Using the TMAs, we characterized the expression of ER, PR, HER2, EGFR, and HER3 by immunohistochemistry. Each case was classified as one of four IHC-based subtypes based on the expression of hormonal receptor (HR) and HER2. The clinicopathological characteristics and survival of 950 patients were analyzed by subtype. In the TNBC subtype, the HER3(+) group showed poorer disease-free survival (DFS, P = 0.010) and overall survival (OS, P = 0.015) than the HER3(-) group. In the HER2 subtype, the HER3(+) group also showed poorer DFS (P = 0.022) and OS (P = 0.077) than the HER3(-) group. However, there was no difference in patients with HR-positive breast cancer. HER3 expression was associated with poor DFS in both the TNBC and HER2 subtypes and poor OS in the TNBC subtype. HER3 overexpression is an important prognostic marker in hormone receptor-negative breast cancer, and further study is needed to clarify the role of HER-3 targeted treatment.

Round block technique without cerclage in breast-conserving surgery.

BACKGROUND: Round block technique is a unique breast resection through periareolar doughnut incision. However, it is more technically challenging and time consuming. We simplified the procedure by exclusion of round block cerclage. The purpose of this study was to introduce our round block technique without cerclage and to evaluate the results of oncological and cosmetic outcomes. METHODS: A total of 92 patients with centrally located breast cancer were treated with breast-conserving surgery using round block technique at Samsung Medical Center from July 2009 to May 2012. All patients had a small breast defect with excised breast volume less than 20 % compared to the total breast volume. We minimized the extent of skin removal and used simple interrupted inverted intradermal sutures without cerclage in doughnut closure. Patient's cosmetic satisfaction was assessed by subjective questionnaires at least 6 months after the operation. RESULTS: The median size of tumors was 1.7 cm (range 0.5-5.0 cm). The average distance of the tumors from the nipple was 2.0 cm (range 0.0-4.0 cm) on sonogram and most of the tumors were located upper breast (82.6 %). The median operative time was 101.5 min (range 55-180), including axillary surgeries. Median follow-up was 12.0 months (range 2-36), and none of patients have developed local recurrence. Up to the longest 3 years of follow-up, favorable cosmetic results have been found in patients treated with round block technique. CONCLUSIONS: Round block without cerclage is technically easy and feasible for centrally located breast tumors with favorable cosmetic results.

A new subfascial approach in open thyroidectomy: efficacy for postoperative voice, sensory, and swallowing symptoms. A randomized controlled study.

BACKGROUND: After open thyroidectomy, patients usually complain of voice, sensory, and swallowing symptoms. We approached the thyroid via the subfascial method to reduce these symptoms and compared postthyroidectomy symptoms with the conventional subplatysmal method. METHODS: Eighty-six patients undergoing thyroidectomy were recruited and randomized into either a conventional subplatysmal approach group (subplatysmal, 42 patients) group or a subanterior fascia of strap muscle approach group (subfascial, 44 patients). Voice symptoms were assessed using the Voice Handicap Index questionnaire and acoustic voice analysis. Sensory alterations were evaluated by the light touch and pain touch methods. Swallowing symptoms were assessed using the Swallowing Impairment Score (SIS) questionnaire, barium swallowing time, and hyoid bone movement range. Each variable was measured preoperatively, and at 2 weeks and 3 months after thyroidectomy. RESULTS: In both groups, the subjective symptoms of voice, sensation, and swallowing were significantly worsened at 2 weeks after operation, but improved 3 months after operation. Patients in the subplatysmal group had worse SIS scores than patients in the subfascial group (p = 0.016) and delayed barium swallowing time 2 weeks after operation (p = 0.008 compared to preoperative level). In the cohort over 50 years of age, SIS score did not recover to preoperative levels in the subplatysmal group 3 months after operation (p = 0.005 compared to preoperative level). CONCLUSIONS: The subfascial approach may be an effective method for reducing postthyroidectomy swallowing symptoms based on swallowing impairment score, especially in patients over 50 years of age.

The clinical meaning of intramammary lymph nodes.

OBJECTIVE: The clinical meaning of intramammary lymph nodes (iMLNs) is uncertain. We wanted to describe the clinical characteristics and understand the implications of iMLNs detected by sentinel LN biopsy (SLNB). METHODS: We reviewed the clinical, radiological and pathological records of women diagnosed with invasive carcinoma of the breast at the Samsung Medical Center between January 2001 and January 2011. A total of 69 patients were identified, and SLNB was performed in 31 patients. RESULTS: Of the 69 patients included in the study, 22 (31.9%) had metastases in iMLNs. The presence of lymphovascular invasion and the number of axillary LN metastases were associated with iMLN metastasis. Of the 31 patients who underwent SLNB, there were no cases with axillary LN metastasis when axillary SLNB was negative, even in cases of iMLN-positive patients. Of the 10 patients in whom intramammary SLNs (iMSLNs) were detected during SLNB, 8 patients without iMLN metastases were also negative for axillary LNs. CONCLUSION: Patients with metastatic iMLNs had more aggressive cancers with lymphovascular invasion and increased axillary LN metastases. When iMSLN was detected by SLNB, performing of axillary dissection could be determined by the status of the iMSLN itself.

Analysis of the effect of breast magnetic resonance imaging on the outcome in women undergoing breast conservation surgery with radiation therapy.

BACKGROUND: It remains uncertain whether MRI identification of additional foci of disease leads to improved outcome. We undertook a study to evaluate the influence of breast MRI on early and long-term outcome. METHODS: Among 1,271 patients undergone breast cancer surgery between January 2005 and December 2006, 785 patients were attempted for BCS. Operative approach and radiologic findings were compared according to MRI use. We reselected 615 patients with unilateral early-stage breast cancer treated with BCS including RT. We compared the histopathologic characteristics and outcomes according to MRI use. RESULTS: In patients attempted for BCS (n = 785), re-excision rates were not significantly different according to MRI use (P = 1.000). Conversion to mastectomy or bilateral cancer surgery were higher in MRI group (P = 0.002). The IBTR rate was higher in the non-MRI group (P = 0.020). Difference in contralateral cancer rate and total recurrence rates failed to reach statistical significance (P = 0.168, 0.383, respectively). Multivariate study after adjustment showed no difference in recurrence rates and IBTR rates between the two groups (hazard ratios 1.34, 6.37 Ps = 0.385, 0.076). CONCLUSION: Use of MRI in patients with early-stage breast cancer did not result in improvement of a patient's outcome.

Is surgical excision necessary in benign papillary lesions initially diagnosed at core biopsy?

Debate continues regarding the use of surgical excision in benign papillary lesions initially diagnosed at core biopsy. The objective of this study is to propose management guidelines for benign papillary breast lesions initially diagnosed at core biopsy. Between January 2003 and January 2006, 76 lesions were identified as benign papillary lesions at initial core needle biopsy (n=68) or vacuum biopsy (n=8). After surgical excision, six of the 68 benign papillary lesions initially diagnosed at core needle biopsy were confirmed as malignant papillary neoplasms, giving a false-negative rate of core needle biopsy of 8.8%. Three of the eight atypical papillomas initially diagnosed at core needle biopsy were confirmed as papillary cancer in final pathology, giving a false-negative rate of 37.5%. In the analysis of the difference between benign papillary lesions and atypia or malignant papillary lesions, malignant papillary lesions were located more peripherally (p=0.005) than benign lesions and were larger (>1.5 cm, p=0.017). It is concluded that atypical papillomas at initial core biopsy or large, clinically peripherally located papillomas (>1.5 cm) need additional surgical excision.

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.

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.].

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.

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.

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.