bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-06-21: Endogenous expression of ERβ variants contributes towards chemotherapy-resistance in the triple negative breast cancer cell line HCC-1806
Authors: Faria M , Gustafsson J-A , Strom A 
Published: May 2019

Abstract
Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERβ and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that the variants of ERβ, namely ERβ1, ERβ2, ERβ4, and ERβ5, contributes to aggressiveness of the TNBC cell line HCC1806 by affecting E-Cadherin expression and chemotherapy sensitivity.
We have previously shown that the HCC1806 cell line expresses all the ERβ variants. To investigate their function we used the recently developed dCas9-KRAB system with Guide RNA for both ERβ promoters 0N and 0K, using 3 guide RNA's for each promoter and we found that expression of panERβ decreased from a ct. of 28 to 33 indicating loss of total ERβ. Treatment of HCC1806 cells with chemotherapy in combination with an ERβ agonist, LY500307, is more effective in reducing cancer cell viability. Knockdown of total ERβ in HCC1806 cells using CRISPR-Cas9 technology, decreased the proliferation and increased chemo-sensitivity to docetaxel agent in cells with the 0K promoter knock down, while cells with the 0N promoter knock down were less affected. Furthermore, after ERβ knockdown, the cell morphology of HCC-1806 changed to a more epithelial phenotype and there was increase in the expression of the classical epithelial marker, E-cadherin. N-Cadherin was unchanged in the cells with the 0K promoter knock down, while E-Cadherin was slightly decreased in cells with the 0N promoter knock down. We also found that cells with the 0K promoter knock down migrated less than control cells in a migration assay, while cells with the 0N promoter knock down were less affected. These findings are in agreement with reports showing that the 0K promoter is responsible for expression of the variants ERβ2 and ERβ5, while the 0N promoter expresses more ERβ1. Furthermore, we have earlier shown that ERβ2 and ERβ5 increase aggressiveness of TNBC via several oncogenic signaling pathways.
In conclusion, knockdown of ERβ variants in HCC-1806 indicated that the variants may be responsible for conferring oncogenic properties to TNBC such as EMT, cancer cell proliferation and chemo-resistance. Therefore, treating TNBC patients with combination therapy including ERβ agonists, may prove to be extremely beneficial for securing better treatment responses and future pre-clinical studies should design appropriate experiments to confirm these findings in vivo.
Citation Format: Faria M, Gustafsson J-A, Strom A. Endogenous expression of ERβ variants contributes towards chemotherapy-resistance in the triple negative breast cancer cell line HCC-1806 [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 P2-06-21.
Abstract P2-07-12: A prognostic prediction nomogram (PDIDC) for breast Paget's disease with infiltrating ductal carcinoma patients: A SEER cohort analysis
Authors: Tan L , Chen K , Jiang WG , You N , Wang Y , Sanders A , Liang G , Liu Z , Ling Y , Zhong W , Tian Z , Gong C 
Published: May 2019

Abstract
Purpose
The aim of the study was to develop a specific nomogram for prediction of prognosis for breast Paget's disease with infiltrating ductal carcinoma (PD-IDC) patients.
Patients and Methods
Patients data were obtained by the Surveillance, Epidemiology, and End Results (SEER) program (N=2502). Study outcome was Breast Cancer Specific Survival (BCSS). Cox proportional hazards model was applied to identify risk factors and develop predictive model. For internal validation, discrimination was calculated with the concordance index (C-index) using the bootstrap method and calibration assessed.
Results
NPI classification, skin symptom, tumor site and age showed significant association with BCSS(table.1)and were used to build the PDIDC nomogram and to calculate risk score. PDIDC nomogram's C-index (0.791, 95%CI 0.783-0.818) showed better discrimination power than NPI classification (0.691, 95%CI, 0.650-0.735, P= 0.000) and AJCC staging (0.718, 95%CI, 0.695-0.741, P=0.000). Patients were divided into high-risk (1882/2502, 75.21%) and low-risk (620/2502, 24.78%) subgroups with the optimal cut-off of risk scores (4.28). The total BCSS of low-risk subgroup was 77.8% (95%CI 74.4%-81.4%) vs. 31.1% (95%CI 19.4-49.8) of high-risk group (P=0.000). Bootstrap internal validation demonstrated an average C-index of 0.739 (95% CI, 0.692-0.746). The nomogram calibration was validated to be accurate in predicting 5-year and 10-year survival.
Variable finally selected for risk predicted model.PredictorHazard RatioP Value95% CINPI classification Good1 Moderate2.170.0001.51-3.14Poor7.260.0004.96-10.63Skin symptom Without1 With1.760.0001.34-2.32Tumor site Centrally located1 Non-centrally located1.250.0421.07-1.56Age*1.010.0001.01-1.03* Continuous variable.
Conclusion
Utilizing NPI classification, skin symptom, tumor site and age, we developed the PDIDC nomogram to predict the 5-year and 10-year BCSS of breast PD-IDC patients.
Citation Format: Tan L, Chen K, Jiang WG, You N, Wang Y, Sanders A, Liang G, Liu Z, Ling Y, Zhong W, Tian Z, Gong C. A prognostic prediction nomogram (PDIDC) for breast Paget's disease with infiltrating ductal carcinoma patients: A SEER cohort analysis [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 P2-07-12.
Abstract P2-08-45: Malic enzyme 1 is a potential metastasis-related biomarker of breast cancer
Authors: Liu C , Tao Z , Hu X 
Published: May 2019

Abstract
Background: Malic enzyme 1 (ME1) catalyzes malate to pyruvate and thus promotes glycolysis, playing a part in the Warburg effect. Recently, several researches have revealed its crucial role in cancer metastasis. KM-plotter, an online analysis tool, showed high ME1 mRNA level was related to poorer RFS and OS. Herein, we explore the prognostic effect of ME1 on invasive breast cancer in Chinese patients and its effect on metastasis in vitro.
Methods: 220 patients with early breast cancer were included in this study. ME1 expression was evaluated semi-quantitatively with tissue microarray-based immunohistochemistry. The relationships between ME1 expression level and clinicopathological features were explored. Survival analyses were carried out by Kaplan-Meier test and COX proportional hazard model. MCF-7 and MDA-MB-468 cell lines were then used for in vitro cell migration and invasion assays.
Results: High expression of ME1 was observed in 51.5% patients. The median follow-up period was 28.9 months (range 0.5-34.0). In correlation analyses, compared with ME1-low cases, ME1-high cases were significantly associated with larger tumor size (P=0.036), positive lymph nodes (P&lt;0.001) and positive lymph-vascular invasion (P=0.003), and tended to be HER2 positive (P=0.094). Survival analysis by Kaplan-Meier test showed high ME1 expression was significantly correlated with poorer recurrence free survival (RFS) (P=0.015). Multivariate analysis identified high ME1 expression as an independent prognostic factor for RFS (P=0.035, HR=5.072 [1.121, 22.942]). Stratified analysis revealed high ME1 expression was related to poorer RFS among cases more than 45 years old (P=0.029, HR=9.833 [1.269, 76.164]) and among those with Ki67 index ≥20% (P=0.038, HR=3.805 [1.074, 13.486]). In vitro, HER2 positive cell line (SKBR3) and TNBC cell lines (MDA-MB-231, MDA-MB-468) showed high expression of ME1, while luminal cell line (MCF-7) showed low expression of ME1. Upregulation of ME1 in MCF-7 cell line remarkably enhanced its ability in migration and invasion, while knockdown of ME1 in MDA-MB-468 cell line had a profound inhibitory effect on migration and invasion.
Conclusions: ME1 enhances migration and invasion of breast cancer cell lines and may be involved in early development of breast cancer metastasis. Thus, ME1 is a promising prognostic indicator and a potential therapeutic target.
Citation Format: Liu C, Tao Z, Hu X. Malic enzyme 1 is a potential metastasis-related biomarker of 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 P2-08-45.
Abstract P2-08-50: Elevated levels of serum tumor marker p53 is a prognostic parameter and a monitoring biomarker for patients who had undergone surgical resection in breast cancer
Authors: Arai M , Nagata T , Sekine S , Baba H , Moriyama M , Hashimoto I , Fujii T 
Published: May 2019

Abstract
Background
Elevated levels of serum tumor maker p53 antibody is expected as an indicator of early diagnosis and a parameter of recurrence in breast cancer. P53 mutation accounts for 20% to 35% in all breast cancer patients. Preoperative high level of anti-p53 antibody in breast cancer patients tend to associate with worse prognosis. This study investigated the prognostic value of preoperative serum p53 levels, and the significance as a biomarker to evaluate a recurrence after surgical resections in breast cancer.
Methods
Preoperative serum p53 concentration levels were measured in total of 259 breast cancer patients, who had undergone either a total mastectomy or a partial mastectomy, through 2010 to 2015 in our facility. Patients with elevated levels of p53 (29 patients) and normal levels of p53 (230 patients) were compared to analyze the association of a marker level with the prognosis and the indication to diagnose recurrence in breast cancer.
Results
Elevated serum level of p53 mutation was identified in 29 (11%) patients. The size of tumor, staging, and pathology did not associate with the level of p53. Patients with elevated serum level of p53 correlated to the high score of nuclear grade (NG2 and NG3) and the high percentage of Ki-67 (&gt;14%), which leading to the worse prognosis. Triple negative breast cancer was the major molecular subtype in the group of high level of p53 comparing with the group of low level of p53. Survival analysis using the Kaplan-Meier method were performed to examine DFS and OS of high serum level of p53 patients. Patients with high level of p53 were significantly showed worse DFS than a normal p53 group. Serum level of p53 was also reflected to the recurrence and metastasis of postoperative breast cancer. There were three patients, who had local recurrences and metastasis, in the group of high levels of p53. Their serum levels of p53 were re-elevated as emerging the local recurrence and metastasis once they had gotten the normal serum levels of p53 after surgical resections. It showed that the increasing of the level of p53 was reflected to the recurrence and metastasis of tumors after surgical resections in breast cancer.
Conclusions
This study suggests that preoperative serum level of p53 can be an independent prognostic parameter and a monitoring biomarker for breast cancer.
Citation Format: Arai M, Nagata T, Sekine S, Baba H, Moriyama M, Hashimoto I, Fujii T. Elevated levels of serum tumor marker p53 is a prognostic parameter and a monitoring biomarker for patients who had undergone surgical resection in 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 P2-08-50.
Abstract P2-08-56: Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller breast cancer
Authors: Zhong W , Tan L , You N , Wang Y , Liang G , Liu Z , Ling Y , Tian Z , Gong C 
Published: May 2019

Abstract
Background It is still controversial to consider age as a prognostic factor into the treatment strategy of patients with T1N0M0 breast cancer.
Aim The main purpose of this study was to evaluate the effect of age on recurrence risk in patients diagnosed with T1N0M0 breast cancer as well as compare the prognosis of young aged patients(YA,≤40 years old) to non-young aged patients(non-YA,&gt;40 years old) by using a propensity score matching(PSM) analysis.
Methods 365 patients with T1N0M0 breast cancer diagnosed between 2003 and 2016 who received surgery in Sun Yat-sen Memorial Hospital Breast Cancer Center were included.The recurrence free survival (RFS) and risk factors for recurrence were identified by using Kaplan-Meier method and Cox proportional hazards models. PSM was then used to reduce the confounding effect of known risk factors on prognosis and then to compare 5-year RFS rates in patients between two age groups.
Results After a median follow up of 79 months, 54 patients developed recurrences and 5-year RFS was 87.6%. YA patients had lower RFS estimates (80.6%), compared to patients diagnosed in a later age (89.1% if older than 40-years old; P = 0.049). YA patients tended to have Her-2 positive, TNBC tumors, higher rate of Ki-67 expression and nuclear grade tumor. At multivariate analysis, Her-2 positive (HR 2.115; 95% CI 1.103-4.055, p=0.024) and TNBC (HR 2.963; 95% CI 1.485-5.914, p=0.002) resulted independent prognostic factors of patient with T1N0M0 breast cancer. In the subgroup analysis, we found significant poor RFS for YA patients with Her-2 positive breast cancer compared to the older counterparts(p=0.006) and YA patients were associated with significantly higher rates of the locoregional recurrence rather than metastasis(p=0.004), especially in first 5 years after diagnosis. After PSM, the baseline level and treatment status including tumor size, grade, HR status, Her-2 status, Ki67 expression breast surgery type and systemic adjuvant treatment(AST) of patients in the two age groups tended to be equal. As result, we found significant difference in the 5-year RFS between two age groups(p=0.008).
Conclusion Based on equal treatment condition, young age at presentation conferred a worse prognosis in patients with T1N0M0 breast cancer is independent on other pathological features.
Citation Format: Zhong W, Tan L, You N, Wang Y, Liang G, Liu Z, Ling Y, Tian Z, Gong C. Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller 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 P2-08-56.
Abstract P2-08-60: Withdrawn
Authors: Lee S , Ahn SH , Son BH , Lee JW , Chung IY , Ko BS , Kim HJ , Kim J , Shon G 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Lee S, Ahn SH, Son BH, Lee JW, Chung IY, Ko BS, Kim HJ, Kim J, Shon G. Withdrawn [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 P2-08-60.
Abstract P2-08-62: Not presented
Authors: Osman MH 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Osman MH. Not presented [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 P2-08-62.
Abstract P2-09-16: CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients
Authors: Crosby EJ , Gwin WR , Chang S , Maecker HT , Lubkov V , Snyder JC , Broadwater G , Hyslop T , Osada T , Hobeika AC , Hartman ZC , Morse MA , Lyerly HK 
Published: May 2019

Abstract
Background: Immune-based therapy for metastatic breast cancer has had limited success. Strategies to augment adaptive immunity include vaccines targeting genomic amplifications like Human Epidermal Growth Factor Type 2 (HER2), an established driver of malignancy. Using a novel alphaviral vector, we constructed a vaccine encoding a portion of HER2 (VRP-HER2).
Methods: In preclinical studies, mice were immunized before or after implantation of hHER2+ tumor cells and HER2-specific immune responses and anti-tumor function were assessed. We then translated this vaccine into a phase I clinical trial in which subjects with advanced HER2-overexpressing breast cancers received VRP-HER2 every 2 weeks for a total of three doses (cohort 1). In cohort 2, subjects received the same dose of VRP-HER2 along with a standard HER2 targeted therapy.
Results: VRP-HER2 induced HER2-specific T cell and antibody responses while controlling tumor growth in murine models. Vaccination with VRP-HER2 was well tolerated in both patient cohorts. PFS was modest, while median OS was 50.2 months in cohort 1 and 32.7 months in cohort 2. In cohort 2, there is one partial response and two patients with continued stable disease. Vaccine induced anti-HER2 antibodies and T cells were identified. Increased perforin expression by memory CD8 T cells post vaccination significantly correlated with improved PFS.
Conclusions: VRP-HER2 led to an increase in perforin expressing HER2-specific memory CD8 T cells in preclinical and clinical studies, and had profound antitumor effects in murine models. The generation of HER2-specific memory CD8 T cells was significantly correlated with increased PFS in patients. Subsequent studies will seek to enhance T cell activity by combination with anti-PD-1/PD-L1 antibodies.
Citation Format: Crosby EJ, Gwin WR, Chang S, Maecker HT, Lubkov V, Snyder JC, Broadwater G, Hyslop T, Osada T, Hobeika AC, Hartman ZC, Morse MA, Lyerly HK. CD8 T cells induced by novel alphaviral vector predict improved progression free survival in advanced HER2+ breast cancer patients [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 P2-09-16.
Abstract P2-13-05: Prevalence of trastuzumab-induced cardiotoxicity in a real-world setting
Authors: Calvillo-Argüelles O , Flores-Diaz D , Gonzalez-Serrano J-P , López-Rojas A , Mendoza-Galindo L , Matus-Santos J-A , Reynoso-Noverón N , Cabrera-Galeana P , Bargalló-Rocha E , Arce-Salinas C 
Published: May 2019

Abstract
Background: Trastuzumab treatment plus adjuvant or neoadjuvant chemotherapy is the standard of care for women with HER2 positive breast cancer. Despite relative low rates of cardiotoxicity observed in randomized clinical trials, trastuzumab interruption driven by LVEF reduction is a major concern in current clinical practice.
Patients and methods: We retrospectively identified women with stage I-III HER2 positive breast cancer who received 12 months of trastuzumab treatment after adjuvant or neoadjuvant chemotherapy at Instituto Nacional de Cancerología (INCan, Mexico City), between 2006 and 2018. Patients were eligible if a pre-therapy MUGA scan and ≥2 subsequent follow-up scans were available. Cardiotoxicity was defined as a ≥10% LVEF reduction to a value &lt; 50%, associated with trastuzumab interruption.
Results: 910 patients were included, with a median age at diagnosis of 50 (24-85) years and a median follow up of 7 (2-11 ) years. Among the whole cohort, 10.3% of patients had diabetes, 15.4% had hypertension, 78% were obese/overweight, and 40% had positive estrogen and/or progesterone receptor status. Anthracycline-based therapy was used in 819 (90%) patients, with a median (doxorubicin equivalent) cumulative dose of 200 mg/m2 (IQR 180-240). The median baseline LVEF was 61.8% (50-88.9). In total, 94 (10.3%) patients developed cardiotoxicity, but symptomatic heart failure was observed in only 31 (3.4%) individuals. In univariable analyses, the development of cardiotoxicity was not associated significantly with cardiovascular risk factors.
Conclusions: In this large single-center cohort, cardiotoxicity rates remain high, thus, interventions to minimize the risk of cardiotoxicity and trastuzumab treatment interruption should be considered.
Citation Format: Calvillo-Argüelles O, Flores-Diaz D, Gonzalez-Serrano J-P, López-Rojas A, Mendoza-Galindo L, Matus-Santos J-A, Reynoso-Noverón N, Cabrera-Galeana P, Bargalló-Rocha E, Arce-Salinas C. Prevalence of trastuzumab-induced cardiotoxicity in a real-world setting [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 P2-13-05.
Abstract P2-13-07: Efficacy of short-course adjuvant trastuzumab in early stage breast cancer
Authors: Saifo M , Nikoula M 
Published: May 2019

Abstract
Background: A total of 12 months adjuvant Trastuzumab is still the optimal choice for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Still, the adjuvant short course 9-week trastuzumab may be considered as a cost-effective and safe option in developing countries such as Syria.
Purpose: The primary objective was disease-free survival after short course adjuvant Trastuzumab therapy in early breast cancer at AI-Bairouni university hospital compared with 6 month of adjuvant trastuzumab , the secondary objective was assessing toxicities especially cardiac toxicity.
Patients and methods: Women with histologically confirmed HER2 positive BC with either positive or negative hormone receptor of stages IA,IIA,IIB,IIC,IIIA,IIIB and IIIC were eligible for the study . Patients were assigned to 2 groups . The initial systemic treatment was similar in the 2 groups . Thereafter, no further Trastuzumab or chemotherapy was administered in Arm A; 90 patients (loading dose 4 mg/kg; then 2mg/kg weekly to complete 9 weeks of T), whereas in Arm B that included 157 patients single-agent T was administered to complete 6 months (loading dose 8 mg/kg then 6 mg/kg every 3 weeks) . The LVEF was measured pretreatment, and every 3 months afterword .
Results: After a median follow up of 24 months DFS was 89.06% and 89.81% in groups A and B respectively (P=0.11).No obvious side effects have been noticed during the follow up period in group A. otherwise congestive heart failure was reported in 2.55% of group B patients .
Conclusion: Short course 9 weeks adjuvant Trastuzumab achieved a good 2 years disease-free survival rate (DFS) compared to 6 month of treatment, with acceptable toxicity and good tolerability for treated patients with early-stage invasive breast cancer. Patients are being monitored for a longer follow up period.
Citation Format: Saifo M, Nikoula M. Efficacy of short-course adjuvant trastuzumab in early stage 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 P2-13-07.