bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-09-31: Crowdsourcing the collateral damage from breast cancer treatment
Authors: Love Susan M , Obidegwu Amaka , Fischetti Christine A 
Published: May 2015

Abstract
INTRODUCTION: Although survivorship research focuses on quality of life after breast cancer treatments, it is usually initiated by providers and focused on previously reported side effects and consequences of treatment. Patients are often reluctant to report side effects they may experience during and after cancer treatment and providers are often reticent to ask. In an effort to explore the patient perspective, the Dr. Susan Love Research Foundation convened a collaboration of advocacy groups to "crowdsource" women’s questions regarding collateral damage from treatment. These concerns will then be incorporated into the Health of Women [HOW] Study, an ongoing, online cohort study of breast cancer open to anyone aged 18 or older.
METHODS: Emails to current HOW participants were sent out July 2013 to solicit questions about collateral damage. In October 2013, we undertook the design of a new website landing page for the submission of questions, partnered with other breast cancer advocacy organizations, and began collecting responses. Responses were then categorized to guide questionnaire development.
RESULTS: Sixteen breast cancer and other advocacy organizations came together to support this project. Emails to current HOW participants resulted in 1191 responses. The website landing page resulted in an additional 3000 responses. Overall, 16.8% of respondents complained of fatigue, 16.3% of memory problems, 15.7% of anxiety and/or depression, and 14.0% of numbness/neuropathy. Other less frequently reported problems included problems with nail growth, vision, hearing, urinary tract infections, and allergy-like symptoms.
CONCLUSION: Through this approach, we received an overwhelming number of responses about collateral damage from treatment. Many of the issues are known side effects, while others are less commonly reported, but debilitating nonetheless. We will next compare responses to previously validated questionnaires, develop a comprehensive collateral damage questionnaire for inclusion in the HOW Study, and generate a report for publication to be distributed to the participants.
Citation Format: Susan M Love, Amaka Obidegwu, Christine A Fischetti. Crowdsourcing the collateral damage from breast cancer treatment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-31.
Abstract P1-15-16: The utilization of hypofractionated breast radiotherapy in the United States between 2003 and 2011
Authors: Huo Dezheng , Hasan Yasmin , Yao Katharine 
Published: May 2015

Abstract
Background: Recently, several randomized trials have found that accelerated hypofractionated whole breast irradiation (HF-WBI) had equivalent local recurrence rates and disease-free survival, compared to conventional fractionated whole breast irradiation (CF-WBI). It is unknown if the pattern of care regarding HF-WBI has changed in the United States after the publication of these trials, given its administrative advantage.
Methods: Using data from the National Cancer Database, this study included 559,362 non-metastasic female breast cancer patients who received post-lumpectomy external beam radiotherapy to their breast or regional nodes. We examined the trend of HF-WBI use in the U.S. and factors related to its use using logistic regression models.
Results: Of patients receiving external beam radiotherapy, about 5% underwent HF-WBI. The most common HF-WBI dose schedule is 42.4-42.6 Gy in 16 fractions without or with boost radiation. There was a 20-fold increased trend in the use of HF-WBI, increasing from about 0.6% in 2003 to 13% in 2011 (p&lt;0.0001). Among patients with pT1-2N0-1 disease, a subgroup for whom previous clinical trials of HF-WBI are mainly applicable, HF-WBI use increased from 0.6% in 2003 to 14% in 2011. Although not included in previous clinical trials, patients with ductal carcinoma in situ also experienced an increased use of HF-WBI, from 0.5% in 2003 to 12% in 2011. We found age was strongly correlated with HF-WBI use; the older a patient, the more likely she received HF-WBI. African Americans were less likely to use HF-WBI. Patients with low grade were more likely to receive HF-WBI than those with high grade and patients with negative nodes are more likely to received HF-WBI. Large volume, academic cancer centers are more likely to adopt HF-WBI than community cancer programs. Interestingly, patients who live at least 50 miles away from a cancer center are about 58% more likely to receive HF-WBI than patients living within 50 miles of a cancer center.
Conclusions: The utilization of hypofractionated radiotherapy significantly increased from 2003 to 2011 in the United States, which is presumably influenced by publication of several randomized trials. In 2011, HF-WBI accounted for more than 10% of all external beam radiotherapy for early breast cancer patients. Patient and facility factors impacted the patterns of HF-WBI use.
Citation Format: Dezheng Huo, Yasmin Hasan, Katharine Yao. The utilization of hypofractionated breast radiotherapy in the United States between 2003 and 2011 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-16.
Abstract P2-05-09: Functional mapping of the oncogenic kinome activity of triple-negative breast cancer cells
Authors: Pan Bo , Mori Miki , Lee Pei Rong Evelyn , Hartog Marij , Sun Qiang , van 't Veer Laura , Coppe Jean-Philippe 
Published: May 2015

Abstract
Background: Triple-negative breast cancer (TNBC) accounts for approximately 10 to 15% of all breast cancer cases. The management of TNBC cases will significantly improve once molecular mechanisms specific to TNBC cells will be identified and treated accordingly. Evidence suggests that TNBC cells display deregulated kinase-dependent signaling cascades that differ from non-triple-negative breast cancer cells. We hypothesized that uniquely divergent phospho-circuits could be distinguished between TNBC and non-TNBC cell lines. By revealing such unique, dysfunctional phospho-signaling network, our long-term objective is to identify kinases that underpin triple-negative breast cancer development, and can be inhibited using targeted therapy.
Methods: The kinome activity of TNBC and non-TNBC cell lines was identified (HCC70, MDA-MB-231, MDA-MB-436 compared to AU565, MCF-7, T47D). The functional phospho-signature of each breast cancer cell was analyzed using a high throughput experimental platform that monitors the level of activity of myriad kinases at once. This technique uses 242 phospho-sensing probes and 78 controls in an aqueous-based assay to simultaneously and directly measure the phospho-catalytic activity of phosphorylating enzymes in cell lysates. We mapped the most significantly deranged phospho-signaling cascades and the related kinases.
Results: Using 6 cell lines tested under various conditions, we generated 72 phospho-signatures, out of a total of 23,040 data points. After validating the repeatability and robustness of the assay, the kinase activity signature of each breast cancer cell line was analyzed and compared to each other using unsupervised hierarchical clustering. The phospho-sensing assay revealed the heterogeneity of kinase activity networks among breast cancer cells. These data also established that phospho-signaling cascades related to AKT, ERK, and SRC kinases were differentially altered in TNBC and non-TNBC cell lines.
Conclusions: We successfully identified unique phospho-circuits of TNBC and non-TNBC cell lines. Our goal is now to test whether specific kinase inhibitors can efficiently kill or prevent the growth of TNBC cell lines in culture and animal models. We will expand our approach into a high-content, functional kinome-screening platform to characterize the phospho-fingerprint of breast cancer cells and tissues, and explore the druggable, kinase-dependent mechanisms critical to triple-negative breast tumors.
Citation Format: Bo Pan, Miki Mori, Pei Rong Evelyn Lee, Marij Hartog, Qiang Sun, Laura van 't Veer, Jean-Philippe Coppe. Functional mapping of the oncogenic kinome activity of triple-negative breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-09.
Abstract P2-06-03: Prostaglandin E receptor EP4 is a therapeutic target in breast cancer stem cells
Authors: Fulton Amy , Kundu Namita , Kochel Tyler , Ma Xinrong , Reader Jocelyn 
Published: May 2015

Abstract
There is an urgent need to identify mechanisms underlying the survival of cells expressing cancer stem cell or tumor-initiating properties. The cyclooxygenase-2 (COX-2) pathway is highly expressed in many breast tumors and contributes to poor outcomes. The COX-2 product prostaglandin E2 (PGE2) promotes tumor growth and metastasis by acting on the G-protein-coupled receptor EP4. We compared the expression and function of COX-2 and EP4 in mammosphere-forming and bulk populations derived from a panel of human and murine luminal and basal type tumor cells with different metastatic capacities. Expression of both EP4 and COX-2 were markedly increased in mammosphere-forming cells derived from basal and/or metastatic cells relative to the bulk population, but neither COX-2 or EP4 levels were elevated in mammospheres derived from luminal or non-metastatic cells. Breast cancer stem cells, expressing elevated EP4 are correspondingly more sensitive to inhibition with EP4 antagonists both in vitro and in limiting-dilution assays in vivo. Somewhat to our surprise, cancer stem cells remain relatively sensitive to lysis by Natural Killer cells. We have also shown that EP4 blockade protects NK cells from tumor-induced immune suppression. These studies identify EP4 as a potential therapeutic target in the general tumor cell population and show that EP4 targeting may selectively inhibit cells with tumor-initiating or stem cell properties. EP4 antagonists can directly inhibit cancer stem cells and tumor metastasis and indirectly support NK-mediated mechanisms of tumor control. We are delineating the mechanisms by which EP4 and COX-2 are upregulated in cells with stem-like properties. In addition to EP4 and COX-2, STAT3 is upregulated in stem cells. Inhibition of STAT3 reduces mammosphere-forming capacity. Our studies support a mechanism whereby COX-2/EP4 signaling induces STAT3 to support breast cancer stem cell survival by a feed-forward mechanism.
Citation Format: Amy Fulton, Namita Kundu, Tyler Kochel, Xinrong Ma, Jocelyn Reader. Prostaglandin E receptor EP4 is a therapeutic target in breast cancer stem cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-03.
Abstract P2-06-06: Mammospheres derived from circulating epithelial tumor cells are an indicator for presence of metastasis in patient with breast cancer
Authors: Pizon Monika , Zimon Dorothea , Pachmann Ulrich , Pachmann Katharina 
Published: May 2015

Abstract
Background:
A major obstacle in the successful treatment of cancer is the occurrence of metastasis. The presence of CETCs is closely related to tumor recurrence, but the mechanisms through which CETCs promote metastasis are still unclear. The aim of this study was to determine the proliferative capacity of CETCs by analyzing the frequency of mammosphere formation with subsequent phenotypic characterization of the spheres arising in breast cancer patients.
Methods:
CETCs were cultured under condition favoring growth of mammospheres from 38 patients with breast cancer, including a subpopulation of 13 patients with metastatic disease. Cell viability, stem cell marker expression and ALDH 1 activity was evaluated by fluorescence scanning microscope (Olympus Scan®R).
Results:
Sphere formation was observed in 74 % of patients with breast cancer. Patients with distant metastasis had higher numbers of mammospheres (median 13,0 vs 1,0; p≤0,001) compared to patients without metastasis. In multivariate analysis, a high number of mammospheres was associated with the presence of metastasis. The mammospheres area under the ROC curve was 0,99. Six or more spheres classified metastatic disease with a sensitivity and specificity of 96 % and 100 %, respectively. These results suggest that above cut-off six in the number of mammospheres is statistically highly indicator for disease progression. Analysis of surface marker expression profile of mammospheres showed that spheres cultured from CETCs had typical phenotype of cancer stem cells with a high enzymatic activity for ALDH 1 with the ALDEFLUOR assay. There was no sphere formation in a control group with 50 healthy donors.
Conclusion
This study demonstrates that a small fraction of CETCs has proliferative activity.
Identifying the CETC subset with cancer stem cells properties may provide more clinically useful prognostic information and may be a new indicator for the presence of metastases.
Citation Format: Monika Pizon, Dorothea Zimon, Ulrich Pachmann, Katharina Pachmann. Mammospheres derived from circulating epithelial tumor cells are an indicator for presence of metastasis in patient with breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-06.
Abstract P2-07-02: IGF1R/FAK crosstalk is essential for epithelial-to-mesenchymal transition (EMT), migration, and invasion of TNBC cells
Authors: Taliaferro-Smith LaTonia D , Oberlick Elaine , Liu Tongrui , McGlothen Tanisha Z , O'Regan Ruth 
Published: May 2015

Abstract
Triple negative breast cancers (TNBCs) are highly metastatic and deadly tumors that currently lack effective prevention and treatment options. Insulin-like growth factor 1 receptor (IGF1R) and focal adhesion kinase (FAK) both play a role in several developmental processes, and both IGF1R and FAK signaling pathways have been linked to a number of common pathological diseases, including breast cancers. In particular, overexpression of IGF1R and FAK are closely associated with metastatic breast tumors. However, the relationship between the IGF1R and FAK signaling cascades in metastatic TNBCs remain largely unknown. The present study aimed to investigate the interrelationship between IGF1R and FAK crosstalk in regulating the malignant properties of TNBC cells. Using stable small hairpin RNA (shRNA)-mediated IGF1R silencing and stable full-length IGF1R plasmid over-expression methods, we demonstrated that IGF1R was essential for maintaining mesenchymal morphologies of TNBC and regulating the expression of EMT markers, including vimentin, ZEB-1, Snail-1, E-cadherin, ZO-1, and claudin-1. Using colony formation, spheroid migration, and Matrigel invasion assays, we further showed that IGF1R promoted migratory and invasive TNBC phenotypes, including increased colony formation, cell migration, and invasion. Most importantly, IGF1R-mediated migration and invasion required FAK activation and could be augmented using pharmacological inhibitors of FAK. Our findings in TNBC cells demonstrate a novel role of the IGF1R/FAK signaling pathway in regulating critical processes involved in the metastatic cascade. These results may improve the current understanding of the basic molecular mechanisms of TNBC metastasis and provide a strong rationale for co-targeting of IGF1R and FAK as therapy for mesenchymal TNBCs.
Citation Format: LaTonia D Taliaferro-Smith, Elaine Oberlick, Tongrui Liu, Tanisha Z McGlothen, Ruth O'Regan. IGF1R/FAK crosstalk is essential for epithelial-to-mesenchymal transition (EMT), migration, and invasion of TNBC cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-07-02.
Abstract P2-07-06: Niclosamid overcomes epithelial-mesenchymal transition of lapatinib resistance through inhibiting Src activation in HER2 positive breast cancer
Authors: Liu Junjun , Chen Xiaosong , Mao Yan , Shen Kunwei 
Published: May 2015

Abstract
Background: The Src pathway is known to regulate tumor matastasis and plays a role in epithelial-mesenchymal transition(EMT). Lapatinib, although, has improved clinical outcome for HER2 positive breast cancer patients, acquired resistance to lapatinib remains an important reason influencing its clinical efficacy. Our previous research shows lapatinib acquired resistance HER2 positive breast cancer cell lines, SKBR3-R and BT474-R have EMT phenomenon and multiple pathway activated. Niclosamide is an FDA-approved antihelminthic agent, which is found has cytotoxicity effect on tumor stem cells recently. We wished to determine the effect of niclosamide on EMT and lapatinib resistance cells and investigate niclosamide as a potential therapeutic agent for HER2 positive breast cancer.
Methods: SKBR3 and BT474, two HER2 positive breast cancer cell lines, were continuously exposed to increasing doses of lapatinib to establish two stable cell lines resistant to lapatinib, SKBR3-R and BT474-R. Cell proliferation was determined by CCK8 assay. Protein expression was determined by western-blotting. Invasion ability was analyzed by transwell assay. FITC staining flow cytometry (FCM) was conducted to observe the percentage of apoptosis.
Results: Both two HER2 positive lapatinib resistant cell lines, SKBR3-R and BT474-R had EMT phenomenon. Niclosamide had a stronger inhibition effect on lapatinib resistant cell lines than parental cell lines, and induced more apoptosis by FCM. Western-blot showed niclosamide could reverse the EMT phenomenon of SKBR3-R and BT474-R with E-cadherin up-regulated and snail,vimentin down-regulated at the concentration of 0.5-1μM. A significant reduction of Src signaling was also confirmed, as well as the downstream Akt and Erk pathway. After adding niclosimide for 48 hours, SKBR3-R and BT474-R’s capability of invasion were inhibited.
Conclusion: Our results suggested that niclosamide had a strong cytotoxic effect on HER2 positive lapatinib resistant breast cancer cell lines. The EMT induced by lapatinib resistance could be reversed by niclosamide, associated with the inhibition of Src pathway activation, as well as the downstream pathways. Niclosamide treatment produced reduced levels of invasion, serving as a novel therapeutic way for lapatinib-resistant breast cancer patients.
Citation Format: Junjun Liu, Xiaosong Chen, Yan Mao, Kunwei Shen. Niclosamid overcomes epithelial-mesenchymal transition of lapatinib resistance through inhibiting Src activation in HER2 positive breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-07-06.
Abstract P2-13-13: Predictors of bilateral mastectomy in breast cancer patients
Authors: Fu Yun , Zhuang Zhigang , Dewing Michelle , Sophia Apple , Helena Chang R 
Published: May 2015

Abstract
Background: Breast cancer surgery has experienced an evolutional change from radical mastectomy to conservative techniques due to the migration of stage of disease at diagnosis and adjuvant use of multimodality treatment. While breast conservation is preferred by most, the trend of bilateral mastectomy has been on the rise in the United States. The aim of this study is to determine factors that may affect patients’ choice of bilateral mastectomy.
Methods: This is a retrospective study of 376 patients diagnosed with primary invasive breast cancer who were treated by bilateral or unilateral mastectomy (BM or UM) at the Revlon/UCLA Breast Center between Jan. 2002 and Dec. 2010. Patients in the bilateral mastectomy (BM) group were further divided into groups of bilateral mastectomy for bilateral breast cancer and for unilateral breast cancer and contralateral prophylactic mastectomy.
Results: When compared with the UM group, the following factors were found to be associated with the BM: younger age (p&lt;0.001), pre-menopause (p&lt;0.001), having a family history of breast cancer (p&lt;0.001) or ovarian cancer (p=0.017), BRCA 1 and 2 mutations (p&lt;0.001, p=0.011, respectively), more breast biopsies (p=0.007), history of breast augmentation (p=0.014), more MRI study within 6 months before the surgery (p=0.029), more likely to have reconstruction surgery (p&lt;0.001) and sentinel lymph node biopsy (SLNB) (p&lt;0.001). Multivariate analysis indicated that patients with smaller tumor size (p&lt;0.001, OR 0.087), negative nodes (p&lt;0.001), sentinel lymph node biopsy as nodal surgery (p&lt;0.001, OR 0.259), BRCA mutation (p=0.020, OR 6.537) and positive family history (p=0.001, OR 2.732) were more likely to choose bilateral mastectomy with reconstruction using tissue expanders or implants (p&lt;0.001, OR 4.546).
Conclusion: Bilateral mastectomy is associated with lower TN stage, requiring only SNLB, presence of BRCA mutation and/or high risk family history. Tissue expanders or implants based reconstructions were more frequently chosen by patients with bilateral mastectomy.
Citation Format: Yun Fu, Zhigang Zhuang, Michelle Dewing, Apple Sophia, Chang R Helena. Predictors of bilateral mastectomy in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-13.