bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES1-3: Advanced technologies to optimize outcomes and minimize toxicities
Authors: Jagsi R 
Published: February 2018

Abstract
Advances in radiation technology offer substantial promise for improving the therapeutic ratio in breast cancer management, both by improving tumor control and by reducing toxicity. Multiple historical randomized trials and their meta-analysis have demonstrated that the benefits of radiation therapy have been accompanied by toxicity to incidentally irradiated structures, including the heart. However, the past two decades have witnessed a dramatic revolution in technological capabilities to allow greater sparing of normal tissues while simultaneously improving the ability to identify and target areas at greatest risk. Intended for the general audience, this presentation will provide an overview of transformative technological advances in radiation oncology in recent years, including three-dimensional conformal treatment planning, intensity modulation, prone positioning, and devices that allow reproducible deep inspiration to facilitate cardiac sparing. It will review the evidence from historical trials that have established the importance of minimizing dose to normal tissues and the heart in particular, as well as more recent data demonstrating excellent dose distributions and promising outcomes with new technologies, motivating their increased utilization. The presentation will include consideration of advances such as the development of contouring atlases to facilitate greater consistency and quality of care. It will also reflect on cost considerations and concerns about rapid uptake of certain technologies prior to studies establishing evidence of benefit, along with a description of ongoing endeavors to assess value. After summarizing new professional society guidelines on whole breast irradiation, it will identify the current consensus recommendations regarding the most appropriate uses of technology to optimize outcomes of whole breast and boost radiotherapy in the modern era. Finally, it will close with a mention of ongoing and future trials evaluating the potential role of even more advanced technologies, such as proton therapy, true inverse-planned intensity modulated radiotherapy, and stereotactic body radiotherapy, in the management of breast cancer.
Citation Format: Jagsi R. Advanced technologies to optimize outcomes and minimize toxicities [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 ES1-3.
Abstract ES10-1: Genetic dissection of cancer development, therapy response, and resistance in mouse models of breast cancer
Authors: Jonkers J 
Published: February 2018

Abstract
Genetically engineered mouse models (GEMMs) and patient-derived xenograft (PDX) models of breast cancer have proven invaluable for basic and translational cancer research. These preclinical models have been useful for in vivo analysis of breast cancer initiation and progression, as well as for investigating anti-tumor efficacy of targeted drugs and immunotherapeutics. However, the establishment of GEMMs and PDX models involves cost and time limitations that represent serious bottlenecks. To keep pace with the growing number of hypotheses that warrant preclinical in vivo testing, continuous refinement of current breast cancer models is crucial. Novel technologies, such as CRISPR/Cas9-based in vivo gene editing, non-germline mouse models of breast cancer, and breast cancer-derived organoids enable accelerated and more refined in vivo and ex vivo modeling of human breast cancer. The resulting preclinical models can be used to identify and validate breast cancer driver genes and candidate drug targets, evaluate anticancer drug efficacy, and identify novel mechanisms of drug resistance.
Citation Format: Jonkers J. Genetic dissection of cancer development, therapy response, and resistance in mouse models of breast cancer [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 ES10-1.
Abstract ES2-2: Clinical management of women with increased breast cancer risk based on histologic lesions
Authors: Degnim AC 
Published: February 2018

Abstract
The objective of this lecture is to review clinical management of women with the following histologic lesions associated with increased breast cancer risk: flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS). Women found to have one or more of these histologic findings in a benign breast biopsy have an increased risk of developing a future breast cancer. Published data will be reviewed that provides estimates of annual and longterm risk associated with these lesions. In addition, management of these lesions after core biopsy will be discussed, specifically the circumstances when surgical excision is recommended. Medical and surgical options for breast cancer risk reduction will be reviewed, as well as their appropriate clinical indications.
Citation Format: Degnim AC. Clinical management of women with increased breast cancer risk based on histologic lesions [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 ES2-2.
Abstract ES3-1: Drugging protein synthesis in cancer therapy
Authors: Schneider RJ 
Published: February 2018

Abstract
Translation of mRNAs that encode proteins with transforming, cell survival, DNA damage DNA repair and angiogenic functions requires increased levels of specific translation factors that are often overexpressed in many human cancers. Translation of these same classes of oncogenic mRNAs also requires increased activation of the protein synthesis machinery, which is stimulated by well-known signal transduction pathways, particularly the P3K-AKT-mTOR pathway and the ERK-MAPK-MNK pathway. Targeted inhibition of selective oncogenic mRNA translation through inhibition of translation-specific signal transduction pathways, or the specific inhibition of certain translation factors that are required in greater amounts for oncogenic mRNA translation, are emerging new areas in human cancer therapeutics and are in active clinical trials. Small molecule drugs have been developed that are highly specific for the key translation factors that are overexpressed in many human cancers, including breast cancers. In breast cancer, specific stage and grade-dependent alterations occur in the translation machinery and in its signal transduction pathways that correspond to locally advanced, inflammatory, endocrine-resistant ER+, hormone receptor negative and metastatic breast cancer. Many of these alterations provide actionable targets with existing drugs for exploitation of translation-specific vulnerabilities that do not target normal cells and can be synergistically combined with existing genotoxic chemotherapies, endocrine therapies, radiation therapy and immunotherapies. Current research has also begun to elucidate previously unknown translational control pathways that provide additional novel targets and potentially lower toxicity approaches. Targeting translational regulation and the protein synthetic machinery in cancer cells provides the advantage of being able to impair the expression of classes of mRNAs that are essential for cancer progression, metastasis and drug resistance, rather than targeting individual proteins or genes. These promising new therapeutics and clinical treatment strategies will be discussed.
Citation Format: Schneider RJ. Drugging protein synthesis in cancer therapy [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 ES3-1.
Abstract ES5-2: Biologic, cultural and health systems influences on breast cancer disparities in Latinas
Authors: Ramirez AG 
Published: February 2018

Abstract
Rationale
Breast cancer is the top cause of cancer-related deaths in Latinas, who more likely than their peers to be diagnosed at advanced disease stage. This makes it critical to reduce the time from screening to diagnosis to treatment. Latinas also face other biologic issues, as well as cultural and linguistic barriers to proper breast cancer care. Patient navigation is a means for providing access to recommended cancer screening services, follow-up, diagnosis, and treatment in medically underserved populations.
Objectives
I led a series of studies to adapt patient navigation for Latino populations, specifically to reduce delays among Latinas to proper diagnoses and care. We trained our bilingual, bicultural patient navigators to help “navigate” underserved people through the complex care system and other barriers to care (finances, transit, child care, language, culture, etc.). Navigation aims to help reduce missed appointments, reduce delays in seeking care, increase follow-up care, and cover the entire ecological framework from policy, community, organizational, interpersonal, and survivor elements.
Results
The series of studies identified Latinas' delays in time to confirmatory diagnosis and start of treatment after an abnormal mammogram; and proved that patient navigation by a bilingual, bicultural patient navigator can reduce Latinas' times to diagnosis and treatment and significantly increase the proportion of Latinas initiating treatment. Our navigation helped patients receive diagnosis 4 times faster, and treatment start 1.5 times faster, than normal. Several aspects of a navigator's services were directly related to achieving these results. As a direct result of our patient navigation activities, we navigated significantly more women from confirmed breast cancer diagnosis to treatment initiation within 30 (69%) and 60 days (97.6%), with much lower rates for non-navigated women.
Conclusion
We conclude—based on a national study that shows women with breast cancer who wait longer than 60 days have a significantly lower survival rate—that our patient navigation is likely to have saved the lives of many Latinas. We have since applied this navigation to achieve greater compliance in following prescribed treatments and improved general and cancer-specific quality of life among cancer survivors. We also, based on these successful results, developed and posted online the Patient Navigator Manual: Developing and Implementing a Patient Navigator Program manual. The bilingual manual outlines the necessary steps and provides tools to incorporate navigation for Latinos at any organization.
Citation Format: Ramirez AG. Biologic, cultural and health systems influences on breast cancer disparities in Latinas [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 ES5-2.
Abstract ES8-3: Circulating complexes of stromal and tumor cells in breast cancer metastasis
Authors: El-Ashry D 
Published: February 2018

Abstract
The establishment of breast cancer metastases at sites distant from the primary lesion site is predicated on the ability of breast cancer cells to mobilize from the primary tumor, survive in circulation, and colonize in a suitable and permissive metastatic niche. While quantitation of individual CTCs has prognostic value in breast cancer patients with metastatic disease, and elevated counts of CTCs may associate with poor outcome in early breast cancer, recent evidence from mouse models indicates that CTCs in clusters have a greater capacity to produce metastases than individual CTCs and new studies in breast cancer suggest that the presence of CTC clusters in patients can be prognostic. We have found in breast cancer patients, clusters of circulating cells that include CTCs, immune cells, and stromal cells found in the tumor microenvironment, specifically cancer associated fibroblasts (CAFs). Like CTC and circulating CAF (cCAF) counts, the incidence and number of CTC/cCAF clusters increases with disease stage.

While the clinical significance of circulating complexes of CTCs and stromal cells remains to be fully elucidated, the recent identification of cCAFs in the peripheral blood of patients with metastatic breast cancer, traveling individually or in clusters with CTCs emphasizes the potential importance of stromal cells as circulating mediators of cancer metastasis. Preclinical murine models of breast cancer metastasis provide opportunities to observe the composition, dynamics, and behavior of these circulating CTC/stromal cell complexes, and to interrogate mechanisms driving their mobilization and clustering. Identifying the cellular components in these circulating complexes, and understanding the mechanisms by which they facilitate breast cancer metastasis, may provide novel therapeutic avenues for the treatment or prevention of metastatic breast cancer.
Citation Format: El-Ashry D. Circulating complexes of stromal and tumor cells in breast cancer metastasis [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 ES8-3.
Abstract GS5-05: Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance)
Authors: Hwang ES , Duong S , Bedrosian I , Allred J , Wisner D , Hyslop T , Caudle A , Guenther J , Hudis C , Winer E , Esserman L , Hylton N 
Published: February 2018

Abstract
Background: Standard treatment for ductal carcinoma in situ (DCIS) consists of surgery, often followed by adjuvant radiation therapy or endocrine therapy. This current approach is thought to represent overtreatment for some patients. This study was undertaken to determine whether an alternate approach of primary endocrine therapy alone could result in measurable radiographic changes in unresected estrogen receptor (ER)-positive DCIS.
Methods: A phase II open-label single arm multi-center cooperative group trial (CALGB 40903) was conducted for postmenopausal patients diagnosed with ER-positive DCIS. All eligible patients underwent baseline mammography and MRI, followed by 6 months of preoperative therapy with letrozole. Follow up breast MRI was obtained at 3 and 6 months of treatment. The primary endpoint was change in total MRI volume of DCIS enhancement from baseline to 3 months and from baseline to 6 months. Secondary endpoints were change in MRI maximum diameter over baseline and change in mammographic extent of disease over baseline. Endpoints were analyzed via 2-sided paired t-tests (a=0.05).
Results: From 8/1/12 to 2/1/16 108 patients were enrolled; Of the 77 patients who completed letrozole treatment per protocol, 66 patients were assessable. 2 additional patients who did not complete treatment per protocol were considered assessable and thus included in the analysis for a total of 68 patients. Median age of the cohort was 62.7 years. DCIS nuclear grade was low in 10% of patients, intermediate in 49%, and high in 40%. 82% of patients had ER-positive, PR-positive DCIS. The total mean MRI volume decreased from baseline to 3 months by 1.93 cm3 (p&lt;0.001) and from baseline to 6 months by 1.82 cm3 (p&lt;0.001). There was no significant difference in tumor volume between 3 and 6 months. Mean total mammographic tumor diameter decreased from baseline to 6 months by 3.31 mm2 (p=0.078).
Conclusions: In a cohort of postmenopausal women treated with 6 months of preoperative endocrine therapy for ER-positive DCIS, MRI volume decreased markedly by 3 months, while mammographic extent of disease was not altered significantly. Correlation of imaging changes with pathology and baseline biomarkers will be conducted. These results will help determine whether MRI could be an effective modality for monitoring treatment response in some patients treated with primary endocrine therapy for ER-positive DCIS.
Citation Format: Hwang ES, Duong S, Bedrosian I, Allred J, Wisner D, Hyslop T, Caudle A, Guenther J, Hudis C, Winer E, Esserman L, Hylton N. Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance) [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 GS5-05.
Abstract MS2-3: Tailoring systemic therapy for patients with lobular breast cancer
Authors: Colleoni MA 
Published: February 2018

Abstract
Recent developments in breast cancer treatment include an increasing awareness of the role of systemic therapies in selected subgroups of patients. A consequence of this strategy is the importance of accurate and reliable histopathological assessment. Through the identification of lobular breast cancer, that account for up to 15% of all invasive breast carcinomas, it is possible to select patients with correlates of responsiveness to therapy other than important indicators of outcome. It was in fact demonstrated that the response to neoadjuvant chemotherapy is significantly lower in lobular breast carcinomas, if compared with the ductal histotype. Also the value of adjuvant chemotherapy in lobular carcinomas was recently questioned, while the magnitude of the effect of adjuvant trastuzumab is similar in lobular and ductal breast cancer. The diagnosis of lobular breast cancer might be relevant also for the selection of endocrine agents in the adjuvant treatment. In particular the relative effectiveness of letrozole compared with tamoxifen was shown to be greater for patients diagnosed with lobular breast cancer. Nevertheless, the use of available information has been limited in tailoring therapy on patients with the lobular subtype, due to the relative rarity of the disease, the absence of prospective studies and the limited number and size of retrospective analysis. The development of effective therapies for these patients should not rely on information mainly contributed from small retrospective analyses. Prospective tailored research through international cooperation is key to make progress and reach consensus on how to treat individual patients with lobular breast carcinomas.
Citation Format: Colleoni MA. Tailoring systemic therapy for patients with lobular breast cancer [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 MS2-3.
Abstract P1-01-08: DPYSL3 modulates proliferation and migration in claudin-low breast cancer
Authors: Matsunuma R , Chan DW , Kim B-J , Singh P , Han A , Malovannaya A , Perou CM , Ellis MJ 
Published: February 2018

Abstract
Cancer is often driven by deregulated protein kinases pathways including breast cancer. To profile the kinome at the protein level we are developing a kinase pulldown (KiP) proteomic platform that uses multiple kinase inhibitors conjugated to sepharose beads for protein kinase profiling. Mass spectrometry-base tryptic peptide sequencing is used to identify and quantify the kinome in an unbiased manner. To date, we have profiled and analyzed the kinomes of more than 50 breast cancer PDX model systems that include all five breast cancer subtypes. In these analyses we have begun to explore the kinome interactome because we have observed that KiP also pulls down breast cancer subtype specific kinase interacting proteins that may represent new biological insights. For example we have consistently identified dihydropyrimidinase-like 3 (DPYSL3) in p21-activated kinase (PAK) inhibitor KiP interactome in the claudin-low WHIM12 PDX model.
DPYSL3 is an intracellular phosphoprotein known to play a role in cell migration and metastasis. However it remains to be seen if DPYSL3 functions as a suppressor or a promoter of metastasis. We therefore generated DPYSL3 knock-down cell lines to evaluate function in claudin-low breast cancer. Proliferation levels of DPYSL3 depleted Claudin-low WHIM12 cells (DPYSL3-) were lower than those of control WHIM 12 (DPYSL3+) cells. In contrast, migration levels of DPYSL3- WHIM12 were greater than those of control cells, suggesting a pivotal role for DPYSL3 in several cellular physiologies. Additionally the activity of a PAK inhibitor (FRAX597) on migration appeared to require DPYSL3, as the inhibitory effect of FRAX579 on migration in WHIM12 was lost when DPYSL3 expression was depleted.
Additionally we find that only the long isoform of DPYSL3, not a short isoform, interacts with PAK to regulate migration, suggesting that alternative splicing of DPYSL3 may an important to the control of migration. Furthermore Snail is also negatively regulated DPYSL3 with elevated expression in DYPSL3- cells.
In conclusion, the study of the kinome interactome in breast cancer PDX identified DPYSL3 as regulator of the PAK family of kinases in a claudin low breast cancer. DPYSL3 is necessary for PAK to promote migration and may play a pivotal role in complex cellular transitions from a proliferative state versus an EMT/cell migratory state.
Citation Format: Matsunuma R, Chan DW, Kim B-J, Singh P, Han A, Malovannaya A, Perou CM, Ellis MJ. DPYSL3 modulates proliferation and migration in claudin-low breast cancer [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 P1-01-08.