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Introduction: To date, the role of immunotherapy with check point inhibitors and/or vaccines in the treatment of breast cancer (BC) is still debating, and the main focus of immunotherapy in BC is on triple negative subtype as a target population in many ongoing clinical trials. Translational research into identifying predictive and prognostic immune biomarkers is of particular clinical relevance, but, there are currently no definite prognostic and predictive immune biomarkers in BC, especially in triple negative breast cancer(TNBC). We investigated the expression profiles of immune genes in patients with TNBC to identify the prognostic value of immune genes in search of clinical implications. Methods : We investigated expression profiles of 770 pan-cancer immune related genes using the nCounter mRNA expression assay (NanoString®) from paraffin-embedded tumor tissues in 200 patients diagnosed as TNBC who received curative surgery at Samsung Medical Center from 2000 to 2004. We analyzed the relationship between stage adjusted level of gene expressions and patients' survival outcomes using Cox regression model. Results: Of 770 genes, 186 genes were selected from univariate analysis with clinical stage adjustment. In multivariate analysis using Cox regression, expressions of CD1B, CD45, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, SPACA3 and RANKL were associated with distant recurrence free survival (p Table 1ParameterParameter EstimateStandard Errorp-valueHazard Ratio95% Confidence Interval(a) distant recurrence free survival Stage2.487350.680570.000312.0293.169, 45.661CD1B1.141910.2753 Conclusion: High expression of IL1RN, PRKCE were associated with short distant recurrence free survival and overall survival in patients with TNBCs who received curative surgery. In contrast, RANKL expression resulted in prolonged distant recurrence free survival and overall survival. Citation Format: Kim J-Y, Jung HH, Lim JE, Cho EY, Lee SK, Yu JH, Lee JE, Kim SW, Nam SJ, Park YH, Ahn JS, Im Y-H. Prognostication of immune related gene expression in patients with triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-30.

Introduction : Our understanding of biology of breast cancer has led to significant changes in diagnostic and therapeutic approaches for breast cancer, The new eighth edition of the TNM classification of the AJCC for breast cancer (BC) determined by a multidisciplinary team of BC experts incorporate biologic factors, such as tumor grade, estrogen and progesterone receptor (ER and PR) expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels in addition to traditional anatomic factors. In this study, we aimed to evaluate prognostic value of this new staging system compared to previous AJCC 7th staging system using single center, long term followed BC cohort. Methods : We conducted a retrospective analysis of women with stage I, II, or III BC who underwent curative surgery with/without adjuvant systemic therapy at Samsung Medical Center between July 2004 and December 2008 (n=3,029). We excluded patients who received neoadjuvant therapy (n=183), and patients with missing information about immunohistochemistry (n=7), HER2 status (n=82) or histologic grade (n=74). The final sample size was 2,683. Results: Of 2,683 BCs, 1,689 (63%) were hormone receptor (HR)-positive(+), 244(9%) were HR+ andHER2+, 289(11%) were HR-negative(-) andHER2+, 461(17%) were triple negative BCs. According to AJCC 7th pathologic staging system, there were 1,135 of stage IA, 4 of IB, 803 of stage IIA, 368 of stage IIB, 258 of stage IIIA, 11 of stage IIIB and 104 of stage IIIC. In terms of 10 year overall survival (OS) according to AJCC 7th staging system, 95.8% in stage IA, 100% in stage IB, 93.5% in IIA, 86.0% in stage IIB, 85.6% in stage IIIA, 90.9% in stage IIIB and 63.6% in stage IIIC were observed (p Conclusions: AJCC 8th clinical staging system provides a good prognostic value and makes up for the weakness of AJCC 7th anatomical pathologic staging. But this system cannot count whole pathologic stages. Modification of AJCC 8th clinical staging system would be warranted. Citation Format: Kim J-Y, Lim JE, Jung HH, Cho SY, Cho EY, Lee SK, Yu JH, Lee JE, Kim SW, Nam SJ, Park YH, Ahn JS, Im Y-H. Validation of the new AJCC eighth edition of the TNM classification for breast cancer with a single center breast cancer cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-32.

Background: Anthracycline (AC) and/or trastuzumab (T) are the most commonly used for neo-/adjuvant therapy for early breast cancer. However, use of those regimens are limited owing to congestive heart failure (CHF). Although reported incidence from pivotal trials is very low and acceptable, no big data-based population study has not been conducted in Koreans yet. The aim of this study was to analyze the incidence, time to occurrence, and risk factors for CHF in patients with early breast cancer, who were treated with AC and/or T therapy, in Korea. Methods: We used the Health Insurance Review and Assessment Service database and included women with no prior history of CHF who were aged >19 years and diagnosed as having early breast cancer between 2007 and 2016. Only patients who had received breast cancer surgery and AC and/or T therapy were included. Patients with metastatic cancer codes were excluded. Result: In total, 86,086 patients were included for this analysis. The incidence and median time to occurrence of CHF according to chemotherapy type were, 3.27% and 683.5 days in the AC only group, 6.39% and 374 days in the AC followed by T group, and 4.43% and 286 days in the T with or without non-AC group, respectively. The multivariate Cox regression analysis revealed that the adjusted hazard ratio (HR) for CHF was increased with older age; in those aged ≥65 years versus Conclusion: This is the first big data-based population study in Korea on the development of CHF after treatment with AC and/or T. The overall incidence of CHF was 3% to 6%, with a median time to occurrence of 1 to 2 years. Adjusted HR increased with older age, AC followed by T therapy, CCI scores ≥2, and preexisting conditions. Table 1. Incidence and median time to occurrence of congestive heart failure according to chemotherapy typeChemotherapy typeTotalCHF event (%)Median time to occurenceAC only66,6992,182 (3.27%)683.5AC followed by T17,0621,090 (6.39%)374T ± non-AC2,325103 (4.43%)286 Table 2. Cox proportional hazards model for congestive heart failure, adjusted for age, chemotherapy type, and Charlson comorbidity index scoreVariableP-valueHR95% CIAge (ref Citation Format: Choi JY, Cho EY, Lee JW, Kim JW, Choi YJ, You JY, Bae SY, Jung SP, Cho KR, Park KH. Incidence and risk factors for congestive heart failure in early breast cancer received anthracycline and/or trastuzumab; big-data analysis of Korean health insurance review and assessment service database [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-09.

Background: Recently, the information in the IHC score was reported to be similar to that in the 21-gene Genomic Health recurrence score (GHI-RS). The aim of this study is to develop a nomogram based on Ki67 index to predict recurrence and to validate the nomogram by comparison with CS-IHC4 as well as Adjuvant! Online and St. Galen risk stratification. In addition, we validated our nomogram with external cohort. Methods: We retrospectively analyzed the clinicopathologic characteristics and outcomes of 1,070 postoperative HR-positive breast cancer patients between 2004 and 2007 at the Samsung Medical Center to determine recurrence-free survival (RFS). We constructed nomogram using Cox proportional hazard model and validated externally in a cohort of 1,028 at Seoul National University Hospital. A prognostic model that used classical variables, Adjuvant! Online, St. Gallen risk stratification, and the four IHC markers (IHC4 score) were created and assessed in our cohort by LR-χ2 test using the bootstrapping method. Results: Nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.70 (95% CI, 0.62–0.75) in the training set. The validation set showed a good discrimination with an AUC of 0.65 (95% CI, 0.58–0.72). In LR-χ2 test, the nomogram score was found to be more informative than the IHC4 with CS (LR-χ2 4.0539 [df1], 95% CI; 0.1038–8.004 for CS-IHC4 + nomogram score vs. CS-IHC4). Prognostic significance was more prominent in N1 diseases than in the others (LR-χ2 4.199, 95% CI; 1.496–6.902 for CS-IHC4 + nomogram score vs. CS-IHC4). However, Adjuvant! Online and St. Galen risk stratification did not show any definitive additional prognostic value. Conclusions: We developed and validated a nomogram based on Ki67 index in external patients' cohort. It was compared with CS-IHC4 in our patients' cohort in early HR-positive breast cancers. This study implicates the amount of prognostic information contained in the nomogram is superior to that in the CS-IHC4 score. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-20.

Background: Crosstalk between growth factor receptor, especially the EGFR/HER2 pathway, and ER pathways has been associated with endocrine resistance. Thus, combination therapy targeting both ER and EGFR/HER2 signaling to block the crosstalk between these pathways and eliminate escape routes have been proven effective in both preclinical and clinical models. Anti-HER2 directed therapy has been reported to restore hormone sensitivity in HER2−positive breast cancers. Adding trastuzumab to conventional treatment has been a standard treatment of choice in HER2−positive breast cancer irrespective of hormonal receptor (HR) status. The purpose of the study is to evaluate adding effect of 1 year of trastuzumab to conventional adjuvant treatment in patients with HER2−positive breast cancer who received surgery according to HR status. Patients and Methods: We retrospectively analyzed the clinicopathologic characteristics and outcomes of 618 postoperative HER2−positive breast cancer patients between 2001 and 2008 at the Samsung Medical Center. Most of HER2−positive patients in our institute were treated with 1 year of trastuzumab as a part of adjuvant therapy since 2007 (post-trastuzumab era) compared with 2000–2006 (pre-trastuzumab era). Clinical outcomes including recurrence-free survival (RFS) were analyzed between pre-trastuzumab and post-trastuzumab era according to HR status. We performed Cox regression multivariate analysis for relapse using variables from univariate analysis by log-rank test for relapse. Clinical presentations and clinicopathologic characteristics were evaluated at the time of recurrence between both eras. Results: The median age at diagnosis was 46 years (range, 22–79). During the median 60.0 months of follow-up, the 5-year recurrence rate was 20.2%. The 618 patients were divided into two groups (patients who received (n=175) and did not receive (n=443) adjuvant trastuzumab). Recurrence rate was much lower in post-trastuzumab era than in pre-trastuzumab era (13.6% vs. 32.3%, p Conclusion: Cross-talk between ER and EGFR/HER2 pathways may mitigate trastuzumab effect in HER2+ve/ER+ve breast cancers. Further study is warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-15.

Background Hormone receptor (HR) positive breast cancers characterized with ER-associated genes are differentiated luminal B from luminal A tumors mainly by proliferation genes. According to NCCN guideline 2011, node positivity has been a main determinant to decide adjuvant chemotherapy with category 1. However, the experts’ panel at the St. Gallen Consensus in 2009 do not provides definite indications to give or withhold chemotherapy in patient group with intermediate criteria including low numbers (1-3, N1) of involved lymph nodes. Thus, in cases of limited number of nodal metastases, the role of biologic factors including Ki67 index needs to be defined. The aims of this study are to evaluate of Ki67 index as a useful surrogate marker to predict recurrence and to avoid unnecessary adjuvant chemotherapy and to develop nomogram based on Ki67 index to determine adjuvant therapeutic options in HR-positive in N0 and N1 breast cancers. Patients and Methods We retrospectively analyzed the clinicopathologic characteristics and outcomes of 953 postoperative HR-positive N0 and N1 breast cancer patients between 2004 and 2007 at the Samsung Medical Center. We constructed nomogram based on Cox regression model using independent factors demonstrated in multivariate analysis and validated externally in a cohort of 895 patients treated at Seoul National University Hospital. Results: In Cox regression multivariate analysis, ER-ve/PgR+ve and Ki67 index were identified as independent factors. Nomogram base on Cox-regression model showed an AUC of 0.75 (95% CI, 0.72−0.77) in the training set. The validation set showed a good discrimination with an AUC of 0.63 (95% CI, 0.60−0.66). We defined low nomogram score as less than 53, and high nomogram score as 53 or more from the cut-off value of the nomogrma ROC curve. Patients who received anthracycline-containing adjuvant chemotherapy with high nomogram scores showed better RFS with statistical significance than those who did not receive anthracycline-containing adjuvant chemotherapy with high nomogram scores (p Conclusion: Ki67 index is useful as a valuable surrogate marker to predict recurrence and to avoid unnecessary chemotherapy. Nomogram based on Ki67 index is constructed and validated to determine adjuvant therapeutic options in HR-positive N0 and N1 breast cancers. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-19.

Background: Capecitabine, one of the widely used cytotoxic agents for breast cancer, achieved high tumor control rate with low toxicity even in heavily-pretreated patients with metastatic breast cancer (MBC). Capecitabine (Xeloda®) is an oral fluoropyrimidine pro-drug that is transformed to fluorouracil (FU) in several steps, the last of which is conversion of 5'-deoxy-5-fluorouridine to FU by TP. And TS is a target enzyme of 5-FU. The primary purpose of this study was to evaluate the role of TS and TP as biomarkers to predict clinical outcomes of capecitabine monotherapy for MBC. Method: Of Three hundreds fifty-three patients with MBC treated with capecitabine at Samsung Medical Center from 2000 to 2008, ninety patients who were previously treated with anthracycline and taxanes containing regimens and had available tissues for immunohistochemical stainings with estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor-2 (HER2), TS, and TP were included in this analysis. All patients had received capecitabine 2000-2500mg/m2/day for 14days q 3 weeks. Results: The median age of these 90 patients was 49 (26-76) years. The response rate (RR) was 25.6% and the disease control rate (DCR) was 65.6%. The median progression-free survival (PFS) and overall survival (OS) from the 1st day of capecitabine monotherapy were 4.8 (95% C.I.; 3.1-6.5) and 26.7 (95% C.I.; 17.1-36.3) months, respectively. High TS expression (TS score ≥100) was more common in patients with triple negative (TN) subtype than in those with other subtypes (16% for HR+, 22% for HER2+, 44% for TN, p=0.023). Median PFS was significantly lower in high TS expression (6.6 vs. 3.0 months; p=0.017) and low TP expression (TP Conclusion: Our data suggests that high TS score and low TP score correlated with shorter PFS for capecitabine monotherapy of patients with anthracycline and taxane pretreated MBC. Potential role of TS, TP expression as predictive markers of capecitabine monotherapy in patient with MBC should be confirmed by prospective studies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-13-04.

Background: Amplification of the human epidermal growth factor receptor 2 (HER2) gene and concomitant protein overexpression are present in 20-25% of breast cancers. HER2 overexpression and/or gene amplification is associated with a worse clinical outcome and an important predictive marker for sensitivity to anthracycline-based chemotherapy and HER2- targeted therapy. In Korea, the HER2 status has usually been assessed by immunohistochemistry (IHC) in the laboratories. To verify the preanalytic, analytic, and postanalytic factors of IHC in multi-institutions, we assessed the interlaboratory variability of HER2 IHC by comparing the local IHC with the central IHC and SISH results, as a first step toward building a nationwide quality assurance program. Methods: The Breast Pathology Study Group of Korean Society of Pathologists collected 1,198 breast carcinoma samples from 7 university-based hospitals and constructed 56 tissue microarray (TMA) blocks with triplicate of 1 mm cores. Local IHC results for HER2 were obtained from 1,130 patients. We performed IHC (PATHWAY anti-HER2/neu (4B5) rabbit monoclonal antibody, Ventana Medical Systems) and SISH (INFORM HER2 DNA Probe Kit, Ventana Medical Systems) for HER2 on the TMA sections using the automated Benchmark platform (Ventana Medical Systems). We interpreted the results according to the American Society of Clinical Oncology/College of American Pathologists guidelines. Results from local IHC were compared with central IHC and SISH. The concordant rates between central IHC and SISH results were also calculated. Results: The total percentage of cases in each category of local IHC score was: 0/1+, 70.4%; 2+, 8.8% (range among hospitals, 0-36%); and 3+, 20.8% (10.8-28.8%). The percentage of central IHC results (1,110 patients) in each category was: 0/1+, 79.7%; 2+, 3.6% (1.1-8.3%); and 3+, 16.7% (13.1-18.8%). SISH results were obtained from 1,033 patients: negative, 79.5%; equivocal, 0.2% (0-1.6%); and positive, 20.3% (19.2-22.6%). SISH amplifications in each local IHC category were observed as follows: 0/1+, 4.3% (0.6-10%); 2+, 18.8% (5.6-66.7%); and 3+, 71.2% (50-97.3%). When considering the central SISH as gold standard, 3% of cases (30/995) were false negative and 6.3% (63/995) were false positive in local IHC. In central lab, the concordance rates between IHC 3+ and SISH-positive, and IHC 0/1+ and SISH-negative were 95.5% and 98%, respectively. Conclusions: The results of central IHC and SISH markedly decreased the interlaboratory variability of HER2 status. The measurement of HER2 gene amplification by SISH was less affected by the preanalytic factors than the measurement of overexpression of HER2 protein by IHC. Because the rate of false positivity is higher than that of false negativity in the local IHC, the quality assurance program needs to be focused on decreasing not only the false negativity, but also the false positivity of HER2 IHC in local laboratories Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-05.

Purpose Basal-like breast cancer, as defined by gene expression profiling, is associated with aggressive phenotype and poor clinical outcome. Recent immunohistochemical validation suggested that basal-like subtype could be characterized by staining for cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) in triple negative breast cancers (TNBCs). Most of studies evaluated surrogate immunopannel of biomarkers to define basal-like breast cancer subtypes only in the TNBCs, although not all basal-like breast cancers are triple negative breast cancers (TNBCs). The significance of basal marker expression in other than triple negative breast cancer remains to be evaluated. To define prognostic impact of basal marker expression in HER2 positive breast cancer, we investigated cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) expression in patients with HER2 positive early breast cancer. Patients and Methods: Biomarker evaluation was performed using five immunohistochemical surrogate panel of estrogen receptor (ER), progesterone receptor (PR), HER2, CK 5/6 and EGFR in HER2 positive early breast cancers. Amplification of HER2 was confirmed by fluorescent in situ hybridization. HER2-positive breast cancer was classified by expression of basal markers (either EGFR or CK5/6) as “basal HER2- positive” (patients with HER2- positive disease who express basal markers) and “non-basal HER2” (patients with HER2-positive disease who did not express basal markers). We compared the prognostic significance of the basal marker expression between two groups. RESULTS: HER2 overexpression was found in 24.8% of early breast cancers with available tissue specimens from the primary tumor (236 of 952 cases). Basal marker co-expression was identified in 12.7% of HER2 positive early breast cancers. (30 of 236 patients) Basal HER2 positive breast cancer was significantly associated with age greater than 50 years (P=0.012), absence of ER (P < 0.001) and PR (P=0.004). The basal marker co-expression in patients with HER2 amplified early breast cancers demonstrated poorer overall survival (basal positive vs. basal negative, 85.6 months [95% confidence interval (CI), 70.8- 100.3 months] vs. 122.3 [C.I. 133.7-139.9], P=0.001) and disease free survival (DFS) (44.6 months [95% CI, 14.7-74.8] vs 110.7 months [95% CI, 96.4-123.9]; P=. 008) respectively. In lymph node positive group, basal marker expression retained its statistical significance at the multivariate level (P=0.047) HER2 positive breast cancer with lymph node involvement with basal marker expression showed substantially poorer overall survival with 2.1-fold (95% CI, 1.0-4.2) risk for death. CONCLUSION: Considerable number of HER2 positive breast cancer co-expressed basal markers. Our data demonstrated that simultaneous basal marker expression in HER2 positive early breast cancer is associated with poor clinical outcome. The molecular significance of basal marker expression in HER2 positive breast cancer needs to be further investigated. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-03.

Background: Differentiation by multigene signatures with excellent performance of hormone receptor (HR)-positive BC largely related to their proliferation genes. Despite questions about its usefulness, there is increasing evidence that Ki67 is a valuable prognostic marker. Standardization of Ki67 pathological assessment is the main problem to interpret reported trials. The aims of the study are to evaluate the role Ki67 as prognostic marker to predict relapse in HR-positive BC patients (luminal A and B) in adjuvant setting using prospective patients’ cohort. In addition, cut-off value and significant level of Ki67 were investigated comparing with other biomarkers including HER2 in luminal BCs. Method: We retrospectively analyzed the clinicopathologic characteristics of 1,070 postoperative breast cancer patients including Ki67 and clinical outcomes in terms of relapse free survival (RFS) between 2004 and 2007 at the Samsung Medical Center. Ki67 labelling index was measured in quantitative and semiquantitative method, independently. The percentage of positive nuclei stained for Ki67 was calculated each section based on the approximately 1,000 carcinoma cell nuclei. In addition, Ki67 was graded on a scale from 0 to 4, where 0 = staining of 0-4% of tumor cells, 1 = staining of 5-25% of tumor cells, 2 = 26-50% of tumor cells, 3 = staining of 51-75% of tumor cells, and 4 = staining of more than 76% of tumor cells. ROC curve was drawn to evaluate the usefulness of Ki67 index to get AUC then, find out the proper cut-off value of Ki67 to predict relapse. Multivariate analyses with Cox-regression model were performed. Results: Among 1,564 patients who received curative surgery for invasive breast cancer from January 2004 to June 2007, 1,070 patients with HR-positive were included in this analysis excluding 494 with HER2-enriched or triple negative breast cancer patients. Median follow-up duration was 56.9 months (range 36-77 months). Median age was 46 years (range 22-83 years). Ki67 threshold >19.5%, corresponding to a sensitivity 78.3%, a specificity 51.6% was chosen as cut-off value for relapse in adjuvant patients’ cohort. The AUC was 0.689 (P Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-01.

Background It has been widely accepted that small and node-negative breast cancers have an excellent prognosis and do not generally have clinical benefit from adjuvant chemotherapy. Recently, the role of adjuvant chemotherapy for small node negative breast cancers has been justified in some high-risk patients, which include HER2−positive and triple negative breast cancers. However, the question has been raised as to whether there are some patients who might have benefit from adjuvant chemotherapy in small node-negative HR-positive breast cancers. According to the current 2011 NCCN guideline, 21-gene RT-PCR assay can be considered for tumor size of more than 0.5 cm in HR-positive, HER2−negative cancers. In cases of high recurrence score (≥ 31), adjuvant chemotherapy in addition to endocrine therapy is recommended as category 2B. Because gene array cannot routinely be used in clinical practice and has not been validated in prospective randomized trials and the usefulness of it still needs to be defined, it would be better if there were valuable markers to determine risk for relapse in this setting. We hypothesized that there could be a population who might have clinical benefit from adjuvant chemotherapy in this small node-negative HR-positive tumors. Patients and Methods We retrospectively analyzed the clinicopathologic characteristics and outcomes of 538 postoperative HR-positive (ER-positive and/or PgR-positive) T1b-cN0 breast cancer patients between 2004 and 2007 at the Samsung Medical Center. We performed Cox regression multivariate analysis for relapse using variables from univariate analysis by log-rank test for relapse. Results: The median age at diagnosis was 46 years (range, 22–79). During the median 60.5 months of follow-up, the 5-year recurrence rate was 5.2%. Anthracycline-based adjuvant chemotherapy was administered to 44.8% of the patients. Adjuvant endocrine and radiation treatment were administered to 94.6% and 63.7% of the patients. There were significant differences according to histologic grade (HG), Ki67 index, and age of less than 35 years in univariate analyses regarding RFS (p=0.003, p Conclusion: A patients’ population may exist who have clinical benefit from adjuvant chemotherapy in T1b-cN0 HR-positive breast cancer patients. Ki67 index and age are useful as valuable surrogate markers to predict recurrence and to have benefit from adjuvant chemotherapy in this population. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-11.

1097 Background: Breast cancer (BC) is the second most common cause of brain metastases (BM). Various prognostic indexes such as RPA to predict survival in BM patients have been developed in patien...

1089 Background: TNBC, one of the most aggressive breast cancer subtypes, is of pivotal clinical importance given the lack of therapeutic target. Regulatory T cells (Tregs) including FOXP3 are potent mediators of dominant self tolerance for cancer. However, obscurity as to the identity, stability and suppressive function of Tregs has impeded therapeutic use. Some of TNBCs are thought to be related with immune genes. Interestingly, TNBCs were reported to be associated with higher number of FOXP3 (Bohling et al. Mod Pathol 2008). The aim of this study is to investigate the prognostic significance of FOXP3 in TNBC. Methods: We investigated the number of tumor-infiltrating FOXP3(+) Tregs in formalin-fixed TNBC specimens which patients received palliative treatment in Samsung Medical Center between 1999 and 2007. Immunohistochemistry was used to assess the numbers of CD4(+), CD25(+), and FOXP3(+) Tregs in tumors and normal breast tissues from 86 patients. The number of FOXP3(+) Tregs was calculated as the tota...

632 Background: Understanding recent advances of tumor biology allow us to divide breast cancer (BC) into at least five subtypes. Different therapeutic approaches are needed based on these molecula...

e21081 Background: Activation of the EGFR signaling can lead to the activation of MAPK, PI3K/AKT, the STAT pathway resulting in tumor growth, inhibition of apoptosis, cell migration and invasion. Tumor cells that over-express both EGFR and HER2, exhibit aggressive tumor cell growth, owing to the increased potential for EGFR/HER2 heterodimerization and signaling. HER2 overexpression has been found to correlate with a worse prognosis in breast cancer. However, the clinical significance of EGFR status in the HER2 positive early breast cancer remains to be evaluated. Methods: This study aims to evaluate EGFR status and its clinical impact in HER2 positive in early breast cancer. To address this issue, biomarker evaluation was performed using immunohistochemistry to semiquantitate estrogen (ER), progesterone (PR), HER2, and EGFR expression in the large cohort of cases with early breast cancers. Amplification of HER2 was confirmed by fluorescent in situ hybridization. Results: HER2 overexpression was found in 2...

Background: Breast cancer comprises a heterogeneous group of diseases that vary in morphology, biology, behavior and response to therapy. Triple-negative breast cancer (TNBC) is a subtype of tumors (estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor-2 (HER2) receptor negative) with aggressive clinical behavior which currently lacks effective targeted therapies. TNBC exhibits a distinct pattern of recurrence which is characterized by rapidly rising rate in the first 2 years following diagnosis, a peak at 2-3 years followed by a decline in recurrence risk over the next 5 years. However, some of the TNBC patients show indolent clinical behavior associated with good clinical outcome. This reinforces the notion that TNBC is a heterogeneous group comprising subtypes with different features and clinical outcome. The aim of this study is to classify TNBC into two subgroups at least, each of which has different clinical course and long-term outcome.Methods: We retrospectively analyzed the clinicopathologic characteristics and outcomes of patients with recurred or metastatic TNBC who received palliative treatment from 1999 to 2007 at Samsung Medical Center.Results: One hundred and seventy-three patients with recurrent and/or metastatic TNBC, who were available clinical data, were recognized. Of 173 patients, the number of relapsed patients after curative surgery was 154, and remaining were initially metastatic patients. The median relapse-free survival (RFS) of 154 patients was 23.6 months (95% CI, 20.4-26.8) and the median overall survival from metastasis of all 173 patients was 21.2 months (95% CI, 16.4-26.0). We divided the patients into two groups according to RFS of 36 months. TNM staging did not show any relationship with RFS (median RFS 24, 27, and 21 months for each stage, p=0.135). The TNBC patients who had RFS of 36 months or greater showed better disease control rate (DCR), progression-free survival (PFS) to 1st line palliative chemotherapy and overall survival (OS) than those with RFS of less than 3 years (DCR 55% vs 77%, p=0.022; median PFS 3.6 vs 7.7 months, p=0.0001; median OS 17.4 vs 42.0 months, p=0.0003). The incidence of brain metastases at the time of first metastasis was much more common in patients with shorter RFS than in those with longer RFS (16% vs 3%, p=0.047). Cox-regression multivariate analysis for OS revealed presence of brain metastasis, presence of hepatic metastasis, and RFS of less than 3 years were identified as independent risk factors (HR 2.01, p=0.007 for brain metastasis; HR 1.99, p=0.007 for hepatic metastasis; HR 2.45, p=0.001 for RFS of 3 year or greater). The results of immunohistochemical staining for basal-maker were pending.Conclusion:TNBC may be classified into two subgroups by RFS. The patients who have RFS of 3 year or greater showed significantly better DCR, PFS to palliative chemotherapy and OS than those who have RFS of less than 3 years. Different therapeutic strategies should be considered for each subgroup. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6032.

564 Background: With the increasing use of screening mammography, the proportion of ≤ 1 cm invasive breast cancer is increasing. Identification of breast cancer molecular subtypes has resulted in a better appreciation of the biologic heterogeneity, which is not fully explained by clinicopathologic features including staging system. The aims of this study were: 1) to identify the risk factors of systemic metastases in patients with ≤ 1 cm invasive breast cancer and 2) to investigate the patients group at greatest risk of such failure even in these small tumors. Method: Data were collected retrospectively in the breast cancer registry of our institution for patients with invasive breast cancer from October 1994 to December 2004. Results: Of 4,036 patients who received curative breast cancer surgery, 466 patients who had T1a or T1b breast cancer were identified. 39 patients who received neoadjuvant chemotherapy were excluded in this study. Ipsilateral axillary lymph node involvement was found in 13% (57/427) at the time of surgery. Axillary lymph node involvement was much more common in HER-2 positive group (33% vs 11%, p < 0.0001) and triple negative (TN) group (24% vs 11%, p = 0.002) than in hormone receptor positive group. During median 61 months of follow-up, overall 10 year estimated distant relapse-free survival (DRFS) and overall survival (OS) were 95% and 92%, respectively. Multivariate analysis was conducted in 370 (T1aN0, T1bN0) patients, who had no lymph node involvement. In Cox-regression model, HER-2 positivity and triple negativity were identified as independent prognostic factors to predict DRFS [Hazard ratio (HR) 8.8, p = 0.003 for HER-2 positive group; HR 5.1, p = 0.026 for TN group] and OS (HR 5.0, p = 0.067 for HER-2 positive group; HR 11.1, p = 0.017 for TN group) in T1bN0 tumors. Limiting to T1aN0 tumors, statistical significance was not maintained. Conclusions: Even though T1aN0 and T1bN0 tumors have been known to have a relative low risk of systemic failure, anti-HER-2 directed therapy for HER-2 positive group and new innovative adjuvant systemic treatment for TN group in patients with T1bN0 tumor should be considered. Prospective adjuvant trials should be warranted in these subgroups of patients. No significant financial relationships to disclose.

Abstract #4019 Purpose To estimate the usefulness of PET scan to assess the response of neoadjuvant chemotherapy, PET scan results were compared with conventional imaging modalities(US and MRI). Patients and Methods Fourty-one patients undergoing neoadjuvant chemotherapy between December 2004 and March 2008 were included. PET scan was performed before and after chemotherapy. Pathologic results were classified into two groups; pathological complete response(pCR) and non-pCR. Clinical responses were assessed with the results of imaging modalities such as post-chemotherapy size or pSUV(postTx), size difference between treatment(delta) and reduction rate(RR) of size or pSUV, and they are compared with postoperative pathologic results. Results 7 out of 41 patients (17.1%) had pCR. The results of US shows that postTx size (1.7±1.5cm) of pCR was not dfferent from those of non-pCR (3.6±3.0cm), and the delta (3.1±1.9cm) and RR (67.7±29.1%) of pCR were higher than those of non-pCR (1.3±1.3cm, 31.0±25.4%), respectively. As a result of MRI, postTx size, delta, RR of pCR was differ from those of non-pCR (1.0±1.7cm vs 2.8±1.7cm p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4019.