bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-06-17: A novel interaction of AURKA with MAPK pathway in breast cancer cells as a potential therapeutic target
Authors: Gandhi S , Gil M , Khoury T , Takabe K , Puzanov I , Gelman I , D'Assoro A , Opyrchal M 
Published: May 2019

Abstract
Background: Aurora A (AURKA) is a mitotic kinase responsible for centrosome segregation and mitotic spindle formation. In normal cells, expression of AURKA is highly regulated and is predominantly restricted to G2/M phases of the cell cycle. Unlike healthy cells, cancer cells overexpress AURKA through all phases of the cell cycle resulting in the acquisition of alternate non-mitotic functions. Little is known about cellular functions regulated by AURKA and its interaction with other signaling molecules. Here, we report a novel interaction between AURKA and the mitogen-activated protein kinase (MAPK) pathway at the level of MEK1 in breast cancer cells. This interaction may serve as a novel target as well as demonstrate by an additive cytotoxic effect of AURKA- and MEK1/2-specific inhibitors against estrogen positive (ER+) and triple negative breast cancer (TNBC) cells.
Results: We show that treatment of ER+ HER2- MCF-7, ER- HER2+ SKBR3 and ER- HER2- BT549 cells with AURKA specific inhibitors alisertib, MK8745 and Aurora A Inhibitor I resulted in over 2-fold increase in relative levels of poMEK1/2 and poERK1/2 compared to untreated controls. The activation of the MAPK pathway was rapid with changes seen within 5 min after treatment with AURKA inhibitors and was sustained for at least 48 hours. Treatment with the pan RAF inhibitor TAK-632 did not diminish alisertib-induced poERK and poMEK1/2. Alternatively, treatment with the MEK1/2 specific inhibitor PD0325901 completely abrogated alisertib-induced phosphorylation of MEK1/2 and ERK1/2. In situ proximity ligation and pull down assays demonstrated AURKA and MEK1/2 direct interaction. In vitro kinase assay showed direct phosphorylation of MEK1 by AURKA. Combined treatment of alisertib and PD0325901 in vitro revealed significant additive cytotoxic effect in MCF-7 and BT549 cells when compared to either agent used alone (p&lt; 0.008 and p&lt;0.011; p &lt;0.04 and p&lt;0.028) with early trend toward significance in survival in a BT549 xenograft breast cancer in vivo model.
Conclusions: Our data shows a novel AURKA-MEK1 interaction in breast cancer cells. In depth in vivo analysis is ongoing. The results reveal a promising new strategy for the treatment TNBC patients using a combination of AURKA and MEK1/2 inhibitors.
Citation Format: Gandhi S, Gil M, Khoury T, Takabe K, Puzanov I, Gelman I, D'Assoro A, Opyrchal M. A novel interaction of AURKA with MAPK pathway in breast cancer cells as a potential therapeutic target [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 P2-06-17.
Abstract P2-06-18: Withdrawn
Authors: Kunder R , Fernandez Dunne S , Clutter M , Cristofanilli M , Mendillo M , Vasilopoulos A , Horiuchi D 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Kunder R, Fernandez Dunne S, Clutter M, Cristofanilli M, Mendillo M, Vasilopoulos A, Horiuchi D. 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 P2-06-18.
Abstract P2-06-20: CDC20 is a novel therapeutic target in triple negative breast cancer
Authors: Sharma J , Raicu I , Nguyen J , Udden N , Wang Q , Alluri P 
Published: May 2019

Abstract
Background: Approximately 15% of breast cancers lack expression of Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER-2), and are referred to as Triple Negative Breast Cancer (TNBC). Clinical outcomes in patients with TNBC continue to be poor due to inherently aggressive biology of the disease and paucity of targeted therapies. In this study, we identified Cell Division Cycle protein 20 (CDC20), a key regulatory protein that mediates sister chromatid separation in mitosis, as a novel therapeutic target in TNBC.
Methods: To uncover new drivers of TNBC, we nominated genes that are significantly overexpressed in patients with TNBC, compared to non-TNBCs. After identifying CDC20 as a top hit in this analysis, we used expression microarrays, RNA-seq analyses and Western blotting to assess CDC20 expression levels in breast cancer patients and cell lines. Kaplan-Meier analyses were performed to study the correlation between CDC20 expression levels and clinical outcomes, including recurrence-free survival, metastasis-free survival and overall survival. shRNA-mediated knockdown of CDC20 in TNBC cell lines was employed to study the role of CDC20 in TNBC proliferation, invasion, migration and xenograft growth in mice.
Results: CDC20 was significantly overexpressed in TNBCs (compared to non-TNBCs) in The Cancer Genome Atlas (TCGA) breast dataset, and in several other independent breast cancer datasets, including Curtis, Stickeler and Kao. CDC20 expression was also significantly higher in TNBC cell lines compared to non-TNBC cell lines. Furthermore, expression levels of CDC20 were highly significantly correlated with clinical outcomes, including recurrence-free survival, metastasis-free survival and overall survival. shRNA-mediated knockdown of CDC20 expression in TNBC cell lines, MDA-MB-231 and MDA-MB-468, resulted in decreased proliferation, invasion and migration. Our preliminary findings suggest that CDC20 knockdown also results in inhibition of cell line-derived xenograft growth in mice.
Conclusion: We identified CDC20 is a novel therapeutic target in TNBC. Our findings support development of pharmacologic strategies to inhibit CDC20 function as a potential targeted therapy against TNBC.
Citation Format: Sharma J, Raicu I, Nguyen J, Udden N, Wang Q, Alluri P. CDC20 is a novel therapeutic target in 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 P2-06-20.
Abstract P2-07-11: Prediction of the Oncotype Dx recurrence score (RS) from clinicopathologic factors
Authors: Voutsadakis IA , Thibodeau S , Reed M 
Published: May 2019

Abstract
Background: The Oncotype Dx assay is currently used as an aid to therapeutic decisions for the adjuvant treatment of women with ER-positive, Her2-negative, lymph node-negative or -micrometastatic breast cancer. The recently reported TAILORx study showed that no or minimal benefit is derived from adjuvant chemotherapy in patients with an Oncotype Dx Recurrence Score (RS) of 25 or less.
Methods: Charts of breast cancer patients that had the Oncotype Dx test in our cancer center in a nine-year period were reviewed. Data on demographic, and cancer-specific characteristics of the included patients were extracted. Predicted disease recurrence from the Oncotype Dx test was recorded and correlated with select clinicopathologic characteristics.
Results: Two hundred and thirty patients with ER-positive, Her2-negative, lymph node-negative or micrometastatic breast cancer were included. Mean age was 65 years-old (SD 9.9). Two hundred and three patients (88.3%) were post-menopausal and one hundred and thirty-three patients (57.8%) were 65 years-old or older. Two hundred and nine patients (90.9%) had lymph node-negative disease. Oncotype Dx recurrence score was low (&lt;11) in sixty-four patients (27.8%), intermediate (11-25) in one hundred and forty patients (60.9%) and high (&gt;25) in twenty-six patients (11.3%). High tumor grade and low progesterone receptor (PR) staining by IHC were the two clinicopathologic factors most associated with a high Oncotype Dx RS (x2 test p &lt;0.00001 and Fisher's exact test p &lt;0.0001). A predictive index (PI) was constructed, assigning one point each for grade 3 and PR staining in 20% or less of tumor cells. A PI of 0 was observed in one hundred and thirty-eight patients (60%), a PI of 1 was observed in seventy-one patients (30.9%), and a PI of 2 was observed in twenty-one patients (9.1%). One hundred and thirty-four patients (97.1%) with a PI of 0 had a RS of 25 or less. Patients with a PI of 1 and 2 had a RS of &gt;25 in 12.7% and 61.9% of cases, respectively.
Conclusion: The PI based on tumor grade and PR we propose is a simple predictor of Oncotype Dx RS. 97.1% of patients with a grade 1 or 2 tumor and PR positivity in &gt;20% of tumor cells had a RS of 25 or less. The Oncotype Dx test and its associated cost can therefore be avoided in these patients, especially in low-resource settings.
Citation Format: Voutsadakis IA, Thibodeau S, Reed M. Prediction of the Oncotype Dx recurrence score (RS) from clinicopathologic factors [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 P2-07-11.
Abstract P2-08-05: Withdrawn
Authors: Jaraj D , Ahlgren J , Arnesson L-G , Einbeigi Z , Höijer J , Klintman M , Malmström P , Vikhe Patil E , Sund M , Fredriksson I , Bergh J , Pettersson A 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Jaraj D, Ahlgren J, Arnesson L-G, Einbeigi Z, Höijer J, Klintman M, Malmström P, Vikhe Patil E, Sund M, Fredriksson I, Bergh J, Pettersson A. 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 P2-08-05.
Abstract P2-08-27: Not presented
Authors: Rayen JM , Poole GH , Rhodes C 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Rayen JM, Poole GH, Rhodes C. 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 P2-08-27.
Abstract P2-08-28: Relationship between FDG uptake and neutrophil/lymphocyte ratio in patients with breast invasive ductal cancer
Authors: Fujii T , Yanai K , Tokuda S , Nakazawa Y , Kurozumi S , Obayashi S , Yajima R , Hirakata T 
Published: May 2019

Abstract
Background: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is used to evaluate the glucose metabolic rates of cancers. Several studies have reported that high FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. FDG uptake is influenced by many factors, including inflammation. In this study, we investigated the relationship between FDG uptake and neutrophil/lymphocyte ratio (NLR), which is an indicator of systemic inflammation. Patients and Methods: We retrospectively investigated the cases of 143 consecutive invasive ductal carcinoma patients who had undergone surgery and FDG-PET preoperatively.PET was evaluated using standardized uptake value max (SUVmax). The median SUVmax was 2.5 (range 0-10.5). Thus, we divided the cases into two groups based on the value of SUVmax; low (&lt;2.5) and high (≥2.5). The relationships between SUVmax and clinicopathological features, including NLR, were investigated. Results: Among the143 patients, 73 (51.0%) had high SUVmax in the primary tumor. The analysis revealed that large tumor size (p&lt;0.001), high nuclear grade (p&lt;0.001), the presence of lymphovascular invasion (p&lt;0.001), CRP (p=0.046) and high NLR (p&lt;0.001) were significantly associated with high SUVmax in the primary tumor. There were associations between SUVmax and NLR (r=0.323, p&lt;0.001). Among the 70 cases with low SUVmax, there was no recurrent disease, while 6 cases among the 73 cases with high SUVmax had disease recurrence. It is interesting to note that the group with high SUVmax and low NLR had no recurrent disease. Conclusions: To the best of our knowledge, this is the first report to describe the relationship between FDG uptake and NLR in breast cancer. The present study demonstrated that the finding of preoperative high FDG uptake in breast cancer may be reflective of poor prognosis and that high NLR may be predictive of aggressive features among patients with breast cancer. On the other hand, among breast cancer patients with high SUVmax in the primary tumor, it will be useful to identify the subset of patients with low NLR in order to improve prognostic accuracy.
Citation Format: Fujii T, Yanai K, Tokuda S, Nakazawa Y, Kurozumi S, Obayashi S, Yajima R, Hirakata T. Relationship between FDG uptake and neutrophil/lymphocyte ratio in patients with breast invasive ductal 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 P2-08-28.
Abstract P2-08-29: The impact of time interval between diagnosis and surgery in each type and stage of breast cancer
Authors: Kim J-M , Choi HJ , Kim I , Ryu JM , Yu J , Lee JE , Kim SW , Nam SJ , Lee SK 
Published: May 2019

Abstract
Background: There are many factors that might contribute to the delay of surgery in patients with breast cancer. Previous studies investigate the influence of delay of surgery, but they reported inconsistent results. The purpose of this study was to evaluate the impact of time of surgery on prognosis of breast cancer.
Methods: We performed a retrospective review of the patients with breast cancer, who received surgery between 1992 and 2009, by using data from Korea Breast Cancer Society Registry. Kaplan-Meier survival analysis and Cox regression model were used to evaluate the impact of time to surgery in breast cancer and subgroup analyses were performed for each disease stage and molecular subtype.
Result: A total 14727 patients were included for analysis. Delay of surgery more than 31 days was associated with worse survival for breast cancer [hazard ratio (HR) = 2.16; 95% confidence interval (CI), 1.936-2.408, p&lt;0.001]. Subgroup analyses revealed that over 31 days of surgical delay were significantly associated with worse survival in hormone receptor positive and HER-2 negative (p&lt;0.001), hormone receptor positive and HER-2 positive (p&lt;0.001), hormone receptor negative and HER-2 positive (p&lt;0.001), triple negative (p&lt;0.001) and stage II, III breast cancer patients (p&lt;0.001).
Conclusion: Surgical delay of more than 31 days were independent risk factors for worse outcome of breast cancer in each molecular subtype and breast cancer group except stage 0 and I. Although preoperative evaluation is required, surgical delay should be shortened to enhance survival of breast cancer, especially in patients with tumor size more than 2cm or presence of lymph node metastasis.
Citation Format: Kim J-M, Choi HJ, Kim I, Ryu JM, Yu J, Lee JE, Kim SW, Nam SJ, Lee SK. The impact of time interval between diagnosis and surgery in each type and stage 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 P2-08-29.
Abstract P2-08-35: A significance of SUVmax levels on FDG-PET as a prognostic factor may be mediated by local immune environment of breast cancer
Authors: Fujimoto Y , Higuchi T , Watanabe T , Hida AI , Imamura M , Kitajima K , Miyoshi Y 
Published: May 2019

Abstract
(Background) SUVmax levels (maximum radioactivity concentration per a pixel) on FDG-PET reflect glucose uptake and it is clinically useful as a prognostic factor. It is reported that breast cancer with high levels of SUVmax causes insufficient glucose concentration in stromal tissue, which results in suppressed cytotoxic T-lymphocytes function. These data may indicate that the prognostic significance of SUVmax levels is influenced by local immune environment of breast cancer. The aim of this study is to investigate whether local immune responses of breast cancer affect correlation of SUVmax levels and prognosis.
(Method) The 278 invasive breast cancer patients were recruited who underwent surgery at Hyogo College of Medicine Hospital and whose SUVmax levels in the breast were examined before surgery or neo-adjuvant therapy. The cutoff value of SUVmax levels was set at 3.585. Tumor infiltrate lymphocytes (TILs) were evaluated as a local immune response and the distributions of TILs were divided into three groups, inflamed (intra-tumoral lymphocytes, Inf), immune excluded (peri-tumoral lymphocytes, IE) and immune desert (very few lymphocytes, ID). During follow-up period (median 39 months), 21 patients relapsed.
(Results) Relapse free survival (RFS) in the SUVmax-high group was significantly worse than in the SUVmax–low group (p=0.0026). There was no correlation between TILs distribution patterns and RFS. In the IE+ID group (175 patients) SUVmax levels were not correlated with prognosis, but in the Inf group (103 patients) RFS of SUVmax-high was significantly worse than of SUVmax-low (p=0.0051). In the multivariate analysis including nodal status and nuclear grade, SUVmax levels of the Inf group was an independent prognostic factor.
(Discussion and conclusion) SUVmax levels in primary lesions were correlated with prognosis only in the Inf group and were not in the IE+ID group. A significance of SUVmax levels as a prognostic factor may be diverse depending on the local immune environment of breast cancer. A novel therapeutic strategy such as inducing suppression of glucose uptake in cancer cells is suggested for breast cancer with immune inflamed.
Citation Format: Fujimoto Y, Higuchi T, Watanabe T, Hida AI, Imamura M, Kitajima K, Miyoshi Y. A significance of SUVmax levels on FDG-PET as a prognostic factor may be mediated by local immune environment 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 P2-08-35.
Abstract P2-08-37: The prognostic impact of synaptojanin 2 expression in estrogen receptor α-positive breast cancer patients
Authors: Nishikawa S , Kondo N , Wanifuchi-Endo Y , Hisada T , Uemoto Y , Katagiri Y , Dong Y , Kato H , Takahashi S , Toyama T 
Published: May 2019

Abstract
Background: Synaptojanin 2 (SYNJ2) was reported to be a druggable mediator of metastasis. It is overexpressed and amplified in breast cancer, particularly estrogen receptor α (ERα)-positive breast cancer. SYNJ2 was also shown to promote cell migration and invasion in breast cancer xenograft cultures and lung metastasis in mice. Here, we investigated SYNJ2 mRNA expression in breast cancer patients during long-term follow-up.
Materials and methods: A total of 434 invasive breast cancer tissues were analyzed for SYNJ2mRNA expression using TaqMan PCR, and the correlation of this expression with patient clinicopathological factors was determined. We also examined the expression of markers associated with tumor-initiating capacity, such as SNAI1, SNAI2, and VIM. Survival curves were analyzed using the Kaplan–Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values.
Results: The median follow-up period was 10.7 years. We found positive correlations between high expression of SYNJ2 mRNA and shorter disease-free survival in breast cancer patients (P=0.049), which was limited to ERα-positive patients (P=0.020) and not seen in ERα-negative patients (P=0.863). High SYNJ2 mRNA levels were positively correlated with high tumor grade, ERα negativity, and node positivity. Multivariate analysis indicated that high SYNJ2 mRNA expression was an independent factor for poor disease-free survival in breast cancer patients.
Multivariate analysis of poor disease-free survival DFS Mutivariate All patientsp valueHR (95%CI)Tumor size2cm and fewer1540.43151 (Reference) more than 2cm280 1.19 (0.78-1.85)Lymph node metastasisNegative2190.0001 and fewer1 (Reference) Positive184 5.61 (3.59-9.05) Unknown31 2.40 (0.89-5.48)Grade1,22330.38471 (Reference) 3195 1.20 (0.79-1.81) Unknown6 0.17 (1.78-3.49)ER statusPositive3370.02621 (Reference) Negative97 2.06 (1.87-4.07)PgR statusPositive2930.39511 (Reference) Negative141 1.30 (0.70-2.28)SYNJ2 mRNA expressionlow2170.02251 (Reference) high217 1.57 (1.07-2.34)
Conclusion:High SYNJ2 expression was shown to be an independent predictive factor of poor prognosis in ERα-positive breast cancer patients. SYNJ2 could therefore be used as a candidate biomarker and therapeutic target in breast cancer.
Citation Format: Nishikawa S, Kondo N, Wanifuchi-Endo Y, Hisada T, Uemoto Y, Katagiri Y, Dong Y, Kato H, Takahashi S, Toyama T. The prognostic impact of synaptojanin 2 expression in estrogen receptor α-positive 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 P2-08-37.
Abstract P2-08-44: Not presented
Authors: Allemand C , Calvo MF , Valerio AC , Riggi MC , Corrao F , Orti R , Wernicke A , Zamora L , Paez MC , Lorusso C 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Allemand C, Calvo MF, Valerio AC, Riggi MC, Corrao F, Orti R, Wernicke A, Zamora L, Paez MC, Lorusso C. 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 P2-08-44.
Abstract P2-14-05: Can an internal surgical adhesive facilitate drain-free mastectomy and reduce overall invasiveness?-A prospective, randomized, controlled, multicenter non-inferiority trial
Authors: Eichler C , Paepke S , Ohlinger R , Mathias W , Scheffen I , Lux M , Hadad S , Kiernan T , Whisker L , Kaushik M , King P 
Published: May 2019

Abstract
Introduction: Mastectomy closure without drains has many potential advantages. Flap fixation techniques have shown to be an effective alternative to drains. This study tested the non-inferiority of a surgical adhesive in overall invasiveness compared to standard wound closure with drains. Methods: This trial (ClinicalTrials.gov Identifier: NCT02958449) recruited seventy-seven patients undergoing eighty-four mastectomies +/- SLNB (n=84) at eleven international centers. Procedures were prospectively randomized to standard wound closure with drains (SWC; n=41) or wound closure without drains using a high strength lysine-based adhesive named TissuGlu® (TG; n= 43). The primary outcome measured assessed overall invasiveness using the number of post-operative clinical interventions, including drain removals and needle aspirations. Secondary endpoints included total wound drainage, cumulative days of treatment, days to drain removal and wound healing related complications. A patient questionnaire evaluating quality of life measures was also administered. Results: Subjects in the TissuGlu® group required significantly fewer post-operative clinical interventions (1.25 ± 1.39 TG vs. 2.03 ± 1.45 SWC, p = &lt;.0001) compared to the Control group and had fewer cumulative days of treatment (defined as days of drains being in place and / or days on which an aspiration occurred; 2.14 ± 4.15 TG vs. 5.76 ± 4.02 SWC, p = &lt;0.0001). Presence of a drain was associated with significantly higher pain and lower mobility scores. Conclusion: The study demonstrates that flap fixation with this adhesive can permit drain-free mastectomy closure, reducing overall invasiveness and patient morbidity.
Citation Format: Eichler C, Paepke S, Ohlinger R, Mathias W, Scheffen I, Lux M, Hadad S, Kiernan T, Whisker L, Kaushik M, King P. Can an internal surgical adhesive facilitate drain-free mastectomy and reduce overall invasiveness?-A prospective, randomized, controlled, multicenter non-inferiority trial [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 P2-14-05.