bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES10-1: Recurrent ESR1 mutations activating mutations in breast cancer
Authors: Jeselsohn R 
Published: May 2019

Abstract
Endocrine treatments are the cornerstone treatments in estrogen receptor positive (ER+) breast cancer. Despite their efficacy, resistance to endocrine treatments remains an important clinical challenge. A number of years ago, recurrent estrogen receptor ligand binding domain (LBD) mutations were identified as the most common genomic mechanism of acquired resistance to endocrine treatment in metastatic breast cancer. These mutations were found in about 20% of ER+ metastatic tissue specimens and in more than 30% of patients with metastatic ER+ breast cancer when testing circulating tumor DNA. Pre-clinical studies showed that these mutations lead to constitutional ligand independent transcriptional activity and tumor growth. Recently, we showed that the ER mutations have neomorphic properties that promote metastases. Clinical data, derived mainly from retrospective analyses of clinical trials, indicate that the ER mutations confer resistance to aromatase inhibitors and fulvestrant, and decreased overall survival. A recent study also showed that the Y537S LBD ER mutation is acquired during fulvestrant and palbociclib treatment. Collectively, the ER mutations are important drivers of resistance standard endocrine treatments and confer worse outcomes in ER+ metastatic breast cancer. Clinical trials stratifying patients by ER mutant status or dedicated to patients with the ER mutations are needed to identify therapeutic strategies to target these mutations.
Citation Format: Jeselsohn R. Recurrent ESR1 mutations activating mutations 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 ES10-1.
Abstract ES12-1: BRCA2 and control of transcription: R-loop dynamics
Authors: Venkitaraman A 
Published: May 2019

Abstract
Pathogenic germline mutations affecting the breast cancer genes, BRCA1 and BRCA2, predispose to cancers of the breast, ovary, and other tissues with a high penetrance. Cancer pathogenesis in mutation carriers has been linked to genomic instability following inactivation of the essential cellular functions of the encoded BRCA1 and BRCA2 proteins in DNA repair and the restoration of stalled DNA replication (reviewed in Venkitaraman, Science 343, 1470-5 (2014)). Here, I will discuss emerging evidence that links previously unrecognized functions of the BRCA proteins to carcinogenesis, focusing on BRCA2.
Increasing evidence indicates that heterozygosity for pathogenic BRCA2 mutations suffices for carcinogenesis in experimental models and in human mutation carriers (eg., Skoulidis et al., Cancer Cell 18, 499-509 (2010); Maxwell et al., Nature Commun 8, 319 (2017); Huang et al., Cell 173, 355-370 (2018)). Heterozygous mis-sense mutations in BRCA2 may act trans-dominantly to interfere with the nuclear transport of BRCA2/RAD51 complexes (Jeyasekharan et al., Nature Str Mol Biol 20, 1191-8 (2013)). We have reported recently a gene-environment interaction that may modify carcinogenesis in BRCA2 mutation carriers, wherein exposure to aldehydes, a pervasive class of endogenous and environmental toxins, selectively proteolyzes BRCA2, inducing haploinsufficiency for DNA repair and replication fork stability in cells bearing heterozygous truncating BRCA2 mutations (Tan et al., Cell 169, 1105-18 (2017)). BRCA2-deficient cells accumulate unscheduled RNA-DNA hybrids (R-loops) and genomic damage through an unexpected role of BRCA2 in promoting the switch from promoter-proximal pausing to transcription elongation by RNA polymerase II (Shivji et al., Cell Rep 22, 1031-1039 (2018)). These emerging functions have implications for the pathogenesis and therapy of cancers arising in patients who carry BRCA2 mutations.
Citation Format: Venkitaraman A. BRCA2 and control of transcription: R-loop dynamics [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 ES12-1.
Abstract ES4-2: Treatment morbidity and quality of life considerations
Authors: Whelan T 
Published: May 2019

Abstract
Partial breast irradiation was introduced to reduce treatment times, improve convenience of radiotherapy and reduce radiation exposure to the breast and surrounding normal tissues. A number of techniques have been developed including interstitial brachytherapy, single catheter-based brachytherapy, intraoperative therapy, and 3 dimensional conformal or intensity modulated radiotherapy. The toxicity profile of partial breast irradiation has been dependent on the different techniques used. In general acute toxicity has been less than that observed with whole breast irradiation, particularly for intraoperative approaches where radiotherapy is delivered at the time of breast conserving surgery. Reports of late toxicity have varied. The majority of trials have observed no increase in late toxicity with interstitial brachytherapy and intraoperative treatment when compared to whole breast irradiation. Some studies of 3D conformal radiotherapy have reported an increase in late radiation toxicity such as telangiectasia of the skin and subcutaneous fibrosis of the breast. Limited data are available on cosmetic outcome and quality of life. Again, results to date have varied with some studies reporting similar cosmetic results and others indicating an increase in adverse cosmesis with partial breast irradiation when compared to whole breast irradiation. This presentation will review mature results from completed trials and discuss radiobiological inferences and implications for clinical decision making.
Citation Format: Whelan T. Treatment morbidity and quality of life considerations [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 ES4-2.
Abstract ES5-2: Clinical and molecular profiles to identify who is at risk?
Authors: Dowsett M 
Published: May 2019

Abstract
The persistent risk of recurrence from ER-positive primary breast cancer has been known for many years. It was recently described in detail and in relation to baseline clinicopathologic factors in a meta-analysis by the EBCTCG. This involved nearly 63,000 patients that had been prescribed 5 years of endocrine therapy and had reached the end of that time recurrence-free (Pan et al, NEJM, 2017, 377, 1836). Among other things this revealed that even among patients with T1N0 disease 13% had a distant recurrence between years 5 and 20. Our group have previously created a Clinical Treatment Score (CTS) from nodal status, tumor size, grade, age and type of adjuvant endocrine treatment and validated this for estimating risk of distant recurrence from the time of diagnosis. Drawing on a training dataset of 4,735 patients from the ATAC trial and a validation set of 6,711 patients from the BIG1-98 trial we created the CTS5, a prognostic score of risk from year 5, that features the same factors as CTS other than type of endocrine treatment (Dowsett et al, JCO, 2018, 36, 1941). Of note, only 4/304 patients with one to three positive nodes that were categorized as low risk in the validation set had a distant recurrence between years 5 and 10. The CTS5 calculator can be accessed online at www.cts5-calculator.com.
There are several commercially available molecular profiles that estimate the risk of recurrence over years 0-10 after diagnosis in endocrine-treated primary breast cancer. In the TransATAC study some of these, including the EPClin and PAM50-ROR, show similar prognostic information over years 5-10 (after 5 years of endocrine therapy) as they do over years 0-5 (during endocrine therapy). In contrast, while the Oncotype Recurrence Score (RS) showed similar prognostic information to EPClin and PAM50-ROR in years 0-5 its performance in years 5-10 was substantially worse. Examination of the time-dependent prognostic relationship of each of the individual genes and modules in the RS showed that those patients with higher ER signaling had good prognosis before year 5 but poorer after year 5, suggesting that the cessation of endocrine therapy may lead to this poorer post-5 year outcome (Dowsett et al Clin Cancer Res, 2015, 21, 2763). A broad-based assessment of gene expression in the TransATAC sample set found that there was limited potential to identify a prognostic profile that performed substantially better after 5 years (Buus et al, Breast Cancer Res, 2018, 20, 103). One test, the 7-gene Breast Cancer Index, has reported on a relatively small sample set that it can predict the benefit or not from extended adjuvant endocrine therapy. Further validation studies of this are warranted as well as other tests that provide the same predictive information.
Citation Format: Dowsett M. Clinical and molecular profiles to identify who is at risk? [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 ES5-2.
Abstract ES8-3: Does breast cancer prevention need an 18th amendment? New evidence on alcohol and breast cancer
Authors: Terry M 
Published: May 2019

Abstract
Epidemiological studies have consistently supported an association between alcohol consumption and breast cancer risk for many years. Breast cancer guidelines from many societies, including the American Cancer Society, have also discussed reducing alcohol consumption to help prevent breast cancer. So why aren't more women aware of this association? This talk will review the latest evidence, including more recent mechanistic studies, about the association between alcohol intake and breast cancer as well as newer data about the lack of cardio protective benefit of modest alcohol intake. What evidence do we now have about whether the association with breast cancer risk and outcomes after diagnosis varies by time in life and intensity of drinking patterns?
Citation Format: Terry M. Does breast cancer prevention need an 18th amendment? New evidence on alcohol and 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 ES8-3.
Abstract ES9-1: Optimizing treatment of early stage triple negative breast cancer: Clinical challenges and new scientific horizons
Authors: DeMichele A 
Published: May 2019

Abstract
“Triple negative” breast cancer (TNBC) as defined by the lack of estrogen and progesterone receptors and absence of Her2-overexpression, is challenging due to its aggressive natural history and limited treatment options. However, significant progress has been made in the last decade in understanding the biological diversity of TNBC, its prognosis and approaches to successful treatment. For example, molecular classification by gene expression studies initially identified a basal molecular subtype enriched for TNBC, which was further refined to additional include 4 major subtypes: basal-like, mesenchymal, luminal androgen receptor and immune-enriched. In addition, clear associations between TNBC and mutations in DNA-repair-related genes, especially BRCA-1 and BRCA-2 have been elucidated. These findings have subsequently guided therapeutic development.
The early-stage setting has been the focus of much of this work, as it is clear that patients who have tumors that respond vigorously to chemotherapy preoperatively have a reduced likelihood of later metastatic recurrence compared to those who have poorly-responsive disease. Capitalizing on this knowledge, trials in the neoadjuvant setting have defined the importance of pathologic complete response (pCR) as a surrogate endpoint, and have shed light on differential effects of standard therapy (such as platinums), development of new targeted therapies (such as PARP inhibitors) and the role of immunotherapy.
The high rate of observed recurrence in patients who have high stage disease at diagnosis, or, in particular, residual disease after neoadjuvant therapy, has also led to the launch of clinical trials in the adjuvant and post-neoadjvuant setting designed to specifically address micrometastatic minimal residual disease and therapy resistance. The advantage of the post-neoadjvuant approach to trials amongst patients with residual disease is to decrease the size of adjuvant trials, and allow them to be focused within populations most at risk of recurrence, sparing those with good prognosis the need for additional, potentially toxic treatment.
Despite this progress, there are still many unanswered questions regarding optimal therapy and potential to improve outcomes in TNBC. This session will review the state of the science with regard to biology, new treatment approaches, and the value of both the neoadjuvant and post-neoadjvuant settings in developing optimal approaches to tailor therapy on the basis of risk stratification, reduce recurrence, and improve outcomes for women presenting with triple negative breast cancer.
Citation Format: DeMichele A. Optimizing treatment of early stage triple negative breast cancer: Clinical challenges and new scientific horizons [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 ES9-1.
Abstract ES9-3: Triple negative breast cancer: Current and future directions in metastatic patients
Authors: Chang J 
Published: May 2019

Abstract
Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) with both early and metastatic disease. The poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets and other approaches to treat these patients. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', as well as a subgroup with a high degree of tumor-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. Additional data from trials with antibody drug conjugates have yielded promising results. We discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities.
Citation Format: Chang J. Triple negative breast cancer: Current and future directions in metastatic 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 ES9-3.
Abstract GS3-03: Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: An EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women
Authors: Gray R ,   Early Breast Cancer Trialists' Collaborative Group
Published: May 2019

Abstract
Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: an EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women
Background: Five years of endocrine therapy with tamoxifen and/or an aromatase inhibitor is highly effective in reducing the risk of recurrence but a substantial risk remains after treatment discontinuation. Continuing treatment with an aromatase inhibitor may mitigate this risk.
Methods: We sought individual patient data for meta-analysis from 12 randomised trials that compared 3-5 years of aromatase inhibitor versus no further treatment after five or more years of endocrine therapy. Primary outcomes were recurrence, and breast cancer mortality. Predefined subgroup comparisons were or prior endocrine therapy (tamoxifen alone, tamoxifen then AI, AI alone), site of recurrence (distant, local, contralateral), age, nodal status, tumour size, grade, and period of follow-up (yrs 0-1, 2-5, 5-9, 10+). Five trials randomised 2-3 years prior to treatment divergence and the primary analyses included only women who were recurrence and second primary cancer free and still alive at the point of treatment divergence.
Results: Data have so far been received on 7,488 women (100% of those randomised) in trials of extended AI following tamoxifen alone, 10,796 women (82% 0f 13,192 randomised) following prior tamoxifen then AI, and 959 (23% of 4,229 randomised) following AI alone. Preliminary analyses including 1,617 breast cancer recurrences and 854 breast cancer deaths confirm a 35% reduction in recurrence with extended AI following tamoxifen alone but suggest a more moderate reduction after prior AI therapy. Data from two trials (NSABP B-42 & N-SAS BC 05) contributing ˜5666 women should be available before SABCS to allow definitive analyses.
Conclusion: This meta-analysis will provide the most reliable possible summary of the available evidence to inform clinicians on the efficacy of extending AI therapy compared to stopping AI after about 5 years of endocrine therapy in preventing disease recurrence and death from breast cancer, both overall and in different categories of women.
Citation Format: Gray R, Early Breast Cancer Trialists' Collaborative Group. Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: An EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24,912 women [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 GS3-03.
Abstract GS6-06: Local therapy and quality of life outcomes in young women with breast cancer
Authors: Dominici LS , Hu J , King TA , Ruddy KJ , Tamimi RM , Peppercorn J , Schapira L , Borges VF , Come SE , Warner E , Partridge AH , Rosenberg SM 
Published: May 2019

Abstract
Background: Increasing rates of mastectomy, primarily bilateral mastectomy (BMx), have been most dramatic in young women with breast cancer (BC). Impact on long-term quality of life (QOL) is largely unknown.
Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure, to women dx with BC at age ≤40 in a large prospective cohort study. Demographic and treatment information was obtained by surveys and chart review. Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by surgery types; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q domain scores.
Results: 581 women with stage 0-3 BC completed the BREAST-Q a median of 5.8 years from dx. Median age at dx was 37 (range: 26-40) years; 86% had stage 0, 1 or 2 disease; 28% had breast-conserving surgery (BCS); 72% had mastectomy (Mx), among whom 72% underwent BMx and 89% had reconstruction. Mean BREAST-Q scores (unadjusted) for breast satisfaction, psychosocial, and sexual well-being were lower for patients having unilateral mastectomy (UMx) or BMx compared to BCS; physical function was similar among groups. In multivariate analysis, lower BREAST-Q psychosocial scores were associated with radiation and Mx (UMx or BMx). Lower sexual well-being scores were also associated with Mx. Lower satisfaction with breast scores following radiation were of a clinically significant magnitude (β -8.1 95% CI -11.9- -4.3, p-value 0.03). Lower scores for physical well-being were seen for patients reporting lymphedema and higher for those who had undergone surgery more than 5 years prior. Lower scores across all 4 domains were associated with reported financial distress.
BREAST-Q domain mean scores (SD) BMxUMxBCSp-valueBreast satisfaction60.3 (18.9)59.5 (21.3)65.9 (20.7)0.008Physical well-being78.6 (14.9)79.7 (15.1)78.9 (15.5)0.8Psychosocial well-being68.1 (20.8)70.5 (21.2)76.1 (20.5)&lt;0.001Sexual well-being48.6 (21.3)53.2 (21.7)57.5 (18.7)&lt;0.001SD Standard deviation
Conclusion: Local therapy in young breast cancer survivors may have a persistent impact on their breast satisfaction, psychosocial, and sexual outcomes, with particular effects from UMx or BMx. Socio-economic stressors also appear to play a role. When counseling young women about their surgical decisions, knowledge of potential long-term QOL impact is of critical importance.
Citation Format: Dominici LS, Hu J, King TA, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Partridge AH, Rosenberg SM. Local therapy and quality of life outcomes in young women with 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 GS6-06.
Abstract MS1-2: Deep learning systems for reading mammograms and breast tomosynthesis
Authors: Karssemeijer N 
Published: May 2019

Abstract
Recent breakthroughs in machine learning resulted in powerful techniques that allow reseachers to accelerate development of automated systems for interpreting medical images. With the use of deep learning and very large training databases, limitations of conventional computer aided detection (CAD) systems, which are widely used in mammography, can be overcome. It is expected that in the coming years algorithms will become more accurate that human readers for interpreting screening mammograms. This will enable physicians to substantially increase quality of mammography. It also will reduce the need for human resources, which is important because many countries face challenges with recruitment of mammographers. In the presentation, experimental study results will be presented which illustrate that deep learning systems are approaching the level of performance of human readers and that there is potential to increase the quality of automated interpretation of mammograms and breast tomosynthesis beyond to the level of experts
Citation Format: Karssemeijer N. Deep learning systems for reading mammograms and breast tomosynthesis [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 MS1-2.
Abstract MS1-3: Artificial intelligence to optimize the accuracy and predictiveness of breast cancer pathology
Authors: Beck A 
Published: May 2019

Abstract
Pathologic analysis of patient tissue specimens plays a central role in breast oncology. Recent advances in artificial intelligence and computer vision offer tremendous potential for discovering new pathologic mechanisms of cancer treatment response and identifying new diagnostics for matching patients and therapies. We will discuss these new advances and their potential for accelerating progress in the diagnosis and treatment of breast cancer.
Citation Format: Beck A. Artificial intelligence to optimize the accuracy and predictiveness of breast cancer pathology [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 MS1-3.