bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-21-36: Splenic enlargement and bone marrow hyperplasia in patients receiving trastuzumab-emtansine for metastatic breast cancer
Authors: Kosmin M , Makris A , Jawad N , Miles D , Padhani AR 
Published: May 2019

Abstract
Introduction
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate used for treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. An association between T-DM1 and splenic enlargement was noted anecdotally on sequential whole-body MRI (WB-MRI) examinations. A retrospective analysis of WB-MRI examinations of patients on T-DM1 was undertaken to investigate the hypothesis that an increase in splenic volume is due to either a generalised hyperplasia of the bone marrow and reticulo-endothelial system and/or an increase in portal venous pressure.
Methods
12 patients underwent 29 serial WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow muscle-normalised signal intensity (nSI), water diffusivity (apparent diffusion coefficient, ADC) and fat fraction were measured. Changes in splenic volume were analysed, and correlations between the measured variables were obtained.
Results
An increase in splenic volume was observed in 92% of patients. Mean splenic volume increased from 144cm3 (95%CI 110-177cm3) to 209cm3 (95%CI 161-257cm3) on T-DM1 therapy (p=0.006). Increase in splenic volume correlated with treatment duration (r2=0.71). Increase in normal bone marrow signal was seen (nSI 3.5 to 4.8, p=0.12), along with a decrease in fat fraction (64.3% to 57.3%, p=0.12), and reduced ADC (655µm2/s to 543µm2/s, p=0.11). No consistent changes to portal vein diameter were seen.
Discussion
An increase in splenic volume was consistently observed in patients on T-DM1 therapy. This was unrelated to portal vein changes but correlated with bone marrow hyperplasia. Caution should be applied when assessing metastatic disease in bone to avoid incorrectly attributing T-DM1-related changes in normal bone marrow to disease progression.
Citation Format: Kosmin M, Makris A, Jawad N, Miles D, Padhani AR. Splenic enlargement and bone marrow hyperplasia in patients receiving trastuzumab-emtansine for metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-36.
Abstract P5-14-01: Chemotherapy randomization of the EORTC 10041/ BIG 3-04 MINDACT (microarray in node-negative and 1 to 3 positive lymph node disease may avoid chemotherapy) trial
Authors: Cardoso F , Piccart M , Rutgers E , Slaets L , van 't Veer L , Viale G , Pierga J-Y , Brain E , Causeret S , Golfinopoulos V , Goulioti T , Knox S , Matos E , Neijenhuis P , Nitz U , Passalacqua R , Rubio IT , Saghatchian M , Smilde TJ , Sotiriou C , Stork L , Straehle C , Thomas G , Thompson A , Vrijaldenhoven S , Vuylsteke P , Tryfonidis K , Bogaerts J , Delaloge S 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Abstract P6-10-05: A pilot study of radiation (RT) and CTLA4-mediated checkpoint blockade with tremelimumab for the treatment of breast cancer brain metastases (BCBM)
Authors: McArthur HL , Beal K , Halpenny D , Henrich M , Patil S , Young R , Kaley T , Hamilton N , Hudis C , Wolchok J , Norton L 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Abstract P6-10-08: Preliminary results of a first in human Phase 1 clinical trial to demonstrate safety and feasibility of chimeric antigen receptor T (CART) cells directed against c-Met in the treatment of breast cancer
Authors: Tchou J , Zhang PJ , Levine BL , Zhao Y , Matro J , DeMichele A , Amy C , Schuchter L , Plesa G , Vonderheide RH , June C 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Abstract CS1-1: Polygenic risk scores for breast cancer: Ready or not?
Authors: Evans D 
Published: May 2019

Abstract
There are increasing attempts to try to stratify cancer risks to enable more targeted early detection and prevention strategies and in particular to balance the risks and benefits of population screening for breast cancer. An increasing number of common genetic variants called Single Nucleotide Polymorphisms (SNPs) have been identified which alter breast cancer risk. Although individually their effect sizes are small they can be used multiplicatively to provide a polygenic risk score (PRS) that accurately predicts risk in both the familial and population setting. Although the first 18 SNPs produce a highly calibrated PRS that is ready for use there are now PRSs of 143 or even 313 SNPs that increase risk stratification although with some loss of calibration. Using data from 9362 women in the Predicting the Risk Of Cancer At Screening (PROCAS) study (500 prospective cancers) and 2000 women in the FH-Risk familial cohort (500 prospective cancers) we have validated the PRS alongside mammographic density (density residual-DR) and standard risk factors to assess future risk of different types of breast cancer. The combined score accurately predicts breast cancers rates with 18-21% of women being predicted in the moderate or high risk categories (≥5% 10 year risk) that developed 41.5-45% of the stage 2+ cancers. In contrast SNP143 is able to identify alongside density and standard risk factors 21% of the general population at &lt;1.4% 10-year risk aged 46-73 years who develop only 9% of the breast cancers. These are also more likely to be potentially 'overdiagnosed' grade 1 and DCIS. The SNP143 is also predictive for oestrogen receptor negative cancers using a 20 SNP PRS.
Conclusions: A combined approach using Tyrer-Cuzick, mammographic density and a PRS provides accurate risk stratification not only overall but also for worse prognosis cancers. This provides support for reducing screening intervals in the high and increasing them in the low risk groups. It is high time these highly informative tests were used in risk stratification
Citation Format: Evans D. Polygenic risk scores for breast cancer: Ready or not? [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 CS1-1.
Abstract CS1-2: Breast cancer genetic testing and results in diverse populations
Authors: Kurian A 
Published: May 2019

Abstract
Sequencing multiple (20-100) cancer-associated genes has rapidly become the clinical standard for hereditary cancer risk assessment. In patients with breast cancer and/or ovarian cancer the BRCA1 and BRCA2 genes have been most widely tested, but a significant number of patients are now found to carry pathogenic (or likely pathogenic) variants in many other genes whose cancer risks are less well-characterized. Moreover, multiple-gene sequencing is associated with a higher rate of uncertain results (variants of uncertain significance), which are more prevalent among racial/ethnic minorities.
While pathogenic variants in less well-characterized genes are prevalent, the appropriate management of carriers remains unclear. Questions remain about the magnitude of risk associated with a pathogenic variant in a specific gene; the spectrum of associated cancers; and the extent to which these factors are modified by family cancer history. Data are emerging from epidemiologic studies in various settings. However, clinical practice requires real-time decisions about whom to test, and for which cancers to screen, despite an incomplete evidence base.
This lecture will review the current state of the science on genetic testing for hereditary breast and ovarian cancer risk. We have recently collaborated with genetic testing laboratories to link the results of clinical genetic testing to Surveillance, Epidemiology and End Results (SEER) registry records of &gt;150,000 breast cancer and/or ovarian cancer patients. I will present results from the SEER-GeneLINK research initiative, focusing on the use, correlates and outcomes of genetic testing on the population level.
Citation Format: Kurian A. Breast cancer genetic testing and results in diverse populations [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 CS1-2.
Abstract CS1-3: Moderate penetrance mutations: What to do?
Authors: Domchek S 
Published: May 2019

Abstract
Genetic testing for breast and ovarian cancer susceptibility has expanded beyond sequencing of BRCA1 and BRCA2. Panel testing has allowed for rapid, affordable, and routine testing of multiple genes simultaneously. There is no one standard “panel” – panels range in types and number of genes tested and panel composition is at the discretion of the ordering provider. Some of the genes commonly included have been long associated with specific genetic syndromes with high lifetime risks of the associated cancers, e.g. mutations in PTEN and Cowden's Syndrome, TP53 and Li Fraumeni Syndrome, STK11 and Peutz-Jeghers Syndrome, and CHD1 and Hereditary Diffuse Gastric Cancer. The inclusion of these “high penetrance genes” on broad cancer panels can lead to challenges regarding discussion and management when detected in families which are not syndromic (for example, the discussion of prophylactic gastrectomy in individuals with CDH1 mutations and no family history of gastric cancer). Mutations in other genes are clearly associated with breast cancer but with lower lifetime risks than for BRCA1 and BRCA2; for example, the lifetime risk of breast cancer for a PALB2 mutation is approximately 40-50%, whereas for ATM and truncating CHEK2 mutations this risk is 25-30%. Mutations in BRIP, RAD51C, and RAD51D are clearly associated with ovarian cancer with lifetime risks of approximately 10% (significantly lower than for BRCA1 mutations). This lecture will address the current understanding of associated cancer risks for mutations in genes included in hereditary cancer panels with a focus on implications for risk reduction and treatment.
Citation Format: Domchek S. Moderate penetrance mutations: What to do? [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 CS1-3.
Abstract ES11-2: Current status of diagnosis, monitoring, and non-surgical management of lymphedema
Authors: McLaughlin S 
Published: May 2019

Abstract
Lymphedema (LE) is a common but underreported complication of breast cancer treatment since most studies lack baseline and follow-up measurements or follow-up that is long enough to adequately record true incidence. Contemporary prospective randomized trials continue to document the occurrence of lymphedema after any axillary treatment and note that combination therapy with axillary surgery and radiation nearly doubles LE risk. Over the last 5 years clinicians have witnessed a paradigm shift in the diagnostic practices of LE with concerted efforts focusing on early detection as opposed to reactionary interventions. Controversy however has existed over how to define and diagnose LE and as such the literature surrounding diagnosis is heterogeneous with respect to incidence and recommendations. Existing guidelines emphasize the need for routine monitoring for LE and the critical importance of baseline, bilateral, and longitudinal limb assessments but do not embrace one measurement technique. A growing body of prospective observational data is systematically challenging the value of precautionary behaviors. Further, prospective randomized data demonstrates exercise does not promote the development of LE. Complex decongestive therapy remains the cornerstone of non-surgical LE treatment. With the NCI predicting over 4 million breast cancer survivors in the US by 2024, lymphedema is potentially a significant public health burden.
Citation Format: McLaughlin S. Current status of diagnosis, monitoring, and non-surgical management of lymphedema [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 ES11-2.
Abstract ES12-2: Link between BRCA1 and Pol II pausing in mammary gland development and tumorigenesis
Authors: Li R 
Published: May 2019

Abstract
Breast cancer risk is significantly elevated for women who carry germ-line mutations in the tumor suppressor gene BRCA1. BRCA1-asociated breast tumors are basal-like, yet they originate from luminal progenitor cells. These precancerous cells of origin are defective in luminal differentiation in BRCA1 mutation carriers before any clinical evidence of cancer. While BRCA1 is best known for its functions in double strand break DNA repair and response to DNA replication stress, it is unclear whether loss of these ubiquitously important functions of BRCA1 is sufficient to account for lineage-specific breast tumor development in BRCA1 mutation-carrying women. Filling this longstanding intellectual disconnect could inform more effective risk assessment and disease prevention.
Recent discoveries from others and us challenge the prevailing DNA repair/replication-centric paradigm. First, in vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Using breast tissue of cancer-free BRCA1 mutation-carrying women, we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1 knockout mouse mammary epithelium. Of note, this BRCA1/COBRA1 interaction occurs in a DSB repair-independent manner. Based on these findings, we suggest that as part of its tumor suppressor activity, BRCA1 promotes luminal epithelial differentiation by mitigating Pol II pausing-dependent transcriptional stress at luminal fate genes. We further propose that accumulation of transcriptional stress in BRCA1-deficient luminal cells redirects luminal transcription and alters luminal homeostasis, which ultimately contributes to lineage-specific BRCA1-associated tumorigenesis.
Citation Format: Li R. Link between BRCA1 and Pol II pausing in mammary gland development and tumorigenesis [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 ES12-2.
Abstract ES12-3: BRCA 1/2/3 and p53 in replication fork stability
Authors: Schlacher K 
Published: May 2019

Abstract
Genome instability is a hallmark of cancer, whereby the vast majority of cancer mutations are caused by defective DNA replication processes. BRCA and p53 genes are critical breast cancer suppressors and “guardians of the genome”. Genetically, BRCA and p53 are frequently found co-inactivated in breast cancer patients. The predominant molecular gene functions ascribed to BRCA genes lies in DNA repair, while p53 is best understood for its transcription activities. Yet these respective functions are insufficient to explain cancer patient genotypes and phenotypes. Recently, novel roles for BRCA and p53 genes in stabilizing DNA replication forks that are separable from their canonical functions have been described.
During this session, we will review BRCA-p53 genetic collaborations during embryogenesis and cancer, with focus on their functional convergence at the level of DNA replication fork stability. We will further discuss BRCA/p53 DNA replication functions as critical new and distinct aspects for cancer therapy approaches and patient variant prediction.
Citation Format: Schlacher K. BRCA 1/2/3 and p53 in replication fork stability [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 ES12-3.
Abstract ES3-2: Multidisciplinary management of breast cancer brain metastases
Authors: Tsien C 
Published: May 2019

Abstract
The management of breast cancer brain metastases requires a multi-disciplinary approach. Local treatment approaches including stereotactic radiosurgery (SRS) and surgery remain an integral component in the management of breast cancer patients. Systemic therapies with better penetration across the blood–brain barrier are currently being investigated. In this session, we will review the role of local therapies in the treatment of brain metastases and considerations on combining these different treatment modalities. We wish to exploit the novel interactions of SRS and systemic agents. We will discuss the evolving role of surgery, stereotactic radiosurgery and whole brain radiotherapy in the treatment of breast cancer brain metastases. We will review recent clinical trial data emphasizing the importance of preserving neurocognitive function in these patients and the general impact on current clinical practice. We will discuss issues regarding the optimal timing of systemic therapies in combination with local therapies and their impact on local control. Overall, there is a changing landscape in the treatment of breast cancer brain metastases with greater emphasis on preserving patients' neurologic function. Clinical trial research continues to be a priority. Ultimately, our goal is a significant paradigm shift in the management of breast cancer brain metastases with the prevention of central nervous system (CNS) metastases.
Citation Format: Tsien C. Multidisciplinary management of breast cancer brain metastases [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 ES3-2.
Abstract ES5-3: Late recurrence in ER-positive breast cancer
Authors: Gralow J 
Published: May 2019

Abstract
The risk of recurrence in early stage, ER-positive breast cancer patients persists for 15-20+ years after diagnosis, and never declines to zero. Rates of late recurrence can be reduced by extending tamoxifen therapy beyond 5 years, with additional tamoxifen or a switch to an aromatase inhibitor. The benefits of extending aromatase inhibitors beyond 5 years remains unclear. The benefit of extended adjuvant endocrine therapy for the average early stage breast cancer patient is small. Extended therapy can be associated with serious increased risks, including thromboembolic events and endometrial cancer with tamoxifen, and fractures and possibly cardiovascular events with aromatase inhibitors. Quality of life can also be impacted, including vasomotor symptoms, sexual dysfunction, and arthralgias. Determining which patients have high residual risk of recurrence beyond 5 years, and importantly whether additional therapy is likely to mitigate that risk, has been the subject of considerable recent research.
Tumor size, nodal status and grade of the primary tumor at the time of diagnosis have been shown to be associated with risk of late recurrence in ER-positive breast cancer. Several multi-parameter molecular biomarker assays performed on the primary tumor are able to separate patients into groups at low and high risk for recurrence beyond 5 years when using retrospective data sets. To date, no specific assay has been felt to have high enough level evidence to recommend inclusion in treatment guidelines or use in decision-making regarding continuing, stopping or switching endocrine therapy.
Recent studies have evaluated whether there are better determinants of late risk of recurrence, beyond the biology of the primary tumor, that can be performed years after the original diagnosis. Assays that may predict the presence of dormant tumor cells and late relapse include Circulating Tumor Calls (CTCs), Disseminated Tumor Cells (DTCs) in the bone marrow, and circulating tumor DNA, proteins or metabolites. While early data is promising, further research is needed before incorporating into clinical decision-making. Identifying a biomarker to determine patients most likely to benefit from longer duration endocrine therapy, or additional therapeutic approaches, could help in reducing late relapse as well as minimizing the risk of side effects and overtreatment.
Citation Format: Gralow J. Late recurrence in ER-positive 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 ES5-3.
Abstract ES6-1: Oxidative stress responses in cancer
Authors: Brugge J 
Published: May 2019

Abstract
Generation of reactive oxygen species (ROS), a natural byproduct of oxygen metabolism, occurs in all aerobic organisms at a controlled rate. Cancer cells are subjected to numerous cellular insults, including dysregulated oncogenes and loss of their natural extracellular matrix (ECM) interactions, that lead to the generation of high levels of ROS and selection for upregulation of anti-oxidant programs that allow adaptation to elevated ROS. Although cancer cells possess enhanced canonical antioxidant programs that neutralize ROS, they nevertheless exhibit prominent ROS levels in response to these insults, suggesting the existence of additional programs that allow cancer cells to tolerate elevated ROS.
My presentation will include a discussion of the evolving concepts about the role of oxidative stress and anti-oxidants in distinct processes associated with tumor initiation and progression and the potential for targeting anti-oxidants for therapeutic intervention. In addition, I will describe studies from our laboratory using 3-dimensional culture systems to model early events in breast cancer which have highlighted the critical role of oxidative stress in eliminating aberrantly proliferating breast epithelial cells, as well as the role of endogenous anti-oxidants in promoting proliferation and survival of pre-malignant cells. I will also discuss studies providing evidence for an unconventional mechanism whereby cancer cells co-opt the ROS-activated neuronal Ca2+-permeable TRPA1 channel in order to adapt to oxidative environments.
Citation Format: Brugge J. Oxidative stress responses in 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 ES6-1.