bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES11-2: Neoadjuvant Systemic Treatment (NST): Tailoring Response by Sub-type
Authors: Chang JC 
Published: March 2020

Abstract
Achieving a pathologic complete response (pCR) after neoadjuvant systemic treatment (NST) is clearly associated with improved survival in breast cancer patients, especially with HER2 and triple negative subtypes. In HER2-positive breast cancer patients, the neoadjuvant platform has allowed for the unprecedented accelerated approval for pertuzumab based on improved pCR rates. The KATHERINE trial, in patients who did not achieve pCR following standard trastuzumab/pertuzumab/chemotherapy, demonstrated for the first time that switching to trastuzumab-emtansine (TDM1) led to significant benefit, creating an interesting research paradigm for these high-risk patients with residual disease. For patients with residual disease, the CREATE-X trial demonstrated survival improvement with capecitabine, especially in patients with triple negative disease. New promising agents in the metastatic setting that are being incorporated into NST include immune-check-point inhibitors and cyclin-dependent kinase inhibitors. Evolving technologies like next generation sequencing and gene expression profiles have improved our knowledge regarding the biology of residual disease, and the mechanisms behind treatment resistance, and potentially, metastases. NST allows for testing of new promising treatment regimens - both escalation and de-escalation - depending on sub-types, before surgery. The management and strategies post-NST and the management of residual disease will be discussed.
Citation Format: JC Chang. Neoadjuvant Systemic Treatment (NST): Tailoring Response by Sub-type [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES11-2.
Abstract ES11-3: Local treatments in patients who achieve pathologic complete response
Authors: White J 
Published: March 2020

Abstract
Local regional treatment of breast cancer has been historically based on anatomic extent of disease in the breast and ipsilateral axilla at presentation. An adjustment in this paradigm is evolving as more breast cancer patients receive neoadjuvant systemic therapy with increasingly more effective agents leading to higher rates of pathologic complete response. In the neoadjuvant setting, breast cancer subtype and pathologic complete response (pCR) may prove to have similar influence on local regional treatment as anatomic stage at presentation. In the ALLIANCE-ACOSOG 1071 clinical trial, rates of pCR (breast and axilla) were highest in the triple-negative (38.2%) and HER2-positive (45.4%) cases and similarly had the highest breast conservation rates of 46.3% and 43.8%, respectively. In addition, breast cancer patients that present with clinical N1 axillary involvement and have complete pathologic response can potentially avoid axillary node dissection with careful use of sentinel node biopsy based on the Sentina and SN FNAC trials. It may be that surgical resection will prove unnecessary for breast conservation in select cases with complete clinical and imaging response when breast radiation is intended and clinical trials are underway. Radiation therapy indications have likewise been established from extent of disease when surgery is the first line of therapy. Retrospective analyses of local regional recurrence incidence in neoadjuvant chemotherapy clinical trials demonstrates it is lowest in those with pathologic compete response in the breast and axillary nodes; as shown in a combined analysis of the NSABP B18 and 27 trials and again seen from analysis of the EORTC 10994/ BIG 1-00 trial. The ongoing NRG NSABP B51 RTOG 1304 clinical trial will determine if regional nodal irradiation is beneficial if positive axillary nodes at presentation convert to negative by neoadjuvant chemotherapy. Complete pathologic response may allow complete omission of post mastectomy radiation in some settings as well reduced extent of breast radiation following breast-conserving surgery.
Citation Format: J White. Local treatments in patients who achieve pathologic complete response [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES11-3.
Abstract ES12-1: Clinical indications of PARP1 inhibitors and other targets
Authors: Telli ML 
Published: March 2020

Abstract
Two PARP1 inhibitors, olaparib and talazoparib, garnered regulatory approvals for the treatment of advanced HER2-negative breast cancer associated with a germline BRCA1 or BRCA2 mutation in 2018. The approvals were based on a prolongation of progression-free survival with PARP inhibitor monotherapy compared to non-DNA damaging single agent chemotherapy in the 1st - 4th line metastatic setting. While the availability of these therapies has increased therapeutic options for this group of patients, median progression-free survival ranged from 7 - 8.6 months and no overall survival advantage has been observed to date. While response rates with PARP inhibitor monotherapy are high, development of resistance remains a significant clinical problem. Further, how PARP inhibitor monotherapy compares with platinum-based chemotherapy in this group of patients has been unclear. The recently reported phase III BROCADE 3 clinical trial examining carboplatin and paclitaxel with the addition of veliparib or placebo added important insights. This was the first phase III trial in patients with advanced germline BRCA1 and BRCA2 mutation-associated HER2-negative breast cancer that examined the use of a PARP inhibitor combined with DNA damaging chemotherapy in the 1st-3rd line setting followed by blinded monotherapy after discontinuation of chemotherapy. The median progression-free survival was significantly prolonged with the addition of veliparib (14.5 versus 12.6 months) with 26% of patients in the veliparib arm remaining progression-free at 36 months. Median overall survival was 33.5 months in the veliparib arm compared to 28.2 months in placebo with 44% of patients in the placebo arm crossing over to receive veliparib after disease progression. While important differences exist between these three trials, BROCADE 3 has reported the longest progression-free and overall survival to date with PARP inhibitor therapy in advanced germline BRCA1 and BRCA2 mutation-associated breast cancer. Beyond BRCA1 and BRCA2, PARP inhibitors are also being investigated in homologous recombination deficient advanced breast cancer in a number of clinical trials. In the Talazoparib Beyond BRCA study, high clinical activity was noted in germline PALB2 mutation carriers. The Olaparib Expanded trial is ongoing.
Citation Format: ML Telli. Clinical indications of PARP1 inhibitors and other targets [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES12-1.
Abstract ES2-1: Guiding decisions to omit radiotherapy after breast-conserving surgery for DCIS. Can genomic biomarkers help?
Authors: Rakovitch E 
Published: March 2020

Abstract
Most women diagnosed with ductal carcinoma in situ (DCIS) will be treated with breast-conserving surgery followed by whole breast radiation. We will review the evolving role of genomic biomarkers to personalize radiotherapy treatment recommendations after breast-conserving surgery for DCIS.
Citation Format: E Rakovitch. Guiding decisions to omit radiotherapy after breast-conserving surgery for DCIS. Can genomic biomarkers help? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES2-1.
Abstract ES3-1: Targeted approach to breast cancer surveillance in high risk women: update of the newest technologies and how to use them
Authors: Jochelson M 
Published: March 2020

Abstract
In multiple prospective randomized trials, screening mammography alone has been demonstrated to reduce breast cancer mortality by approximately 30%. These studies did not account for differences in breast cancer risk. With increasing knowledge of factors that increase breast cancer risk including pathologic mutations, thoracic radiation at a young age, strong family history and incidence of some high-risk lesions, it has become clear that supplemental breast imaging might be necessary to improve early breast cancer detection and outcomes in women at increased risk. Additionally, it has become clear that different high-risk categories are associated with different types and presentations of breast cancer and that these differences might also translate into different imaging strategies. This presentation will address the standard breast cancer imaging tools such as Digital Mammography and Ultrasound and compare them with the newest imaging techniques in breast cancer imaging including Digital Breast Tomosynthesis, and physiologic imaging with a relatively new technology for screening: Contrast Enhanced Digital Mammography and Contrast Enhanced Breast MRI to include the most recent data on Abbreviated Breast MRI. There will be a discussion of fine-tuning the screening strategies based on the specific risk factors which will address the ideal frequency of screening, when screening should start and end and the utility of mammography and ultrasound in women undergoing breast MRI.
Citation Format: M Jochelson. Targeted approach to breast cancer surveillance in high risk women: update of the newest technologies and how to use them [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES3-1.
Abstract ES4-3: The genomic landscape of endocrine-resistant metastatic breast cancer
Authors: Razavi P 
Published: March 2020

Abstract
Recent efforts to characterize the genomes of metastatic breast cancers hold promise for understanding the evolution of the disease through comparative analyses with primary breast cancers. However, these analyses have proven challenging due to the number of differences including differences in tumor representation and spatial tumor heterogeneity resulting in less accurate representation of metastatic disease, and temporal heterogeneity often due to the selective pressures of treatments, all of which may independently alter the ongoing natural evolution of the tumor containing disrupted DNA and/or DNA repair processes. Advances in genomic analyses and large repositories of samples with detailed clinical annotation have enabled rational deconvolution of these datasets, revealing novel insights into the unique drivers shaping advanced and lethal disease. In particular, large cohorts of patients with exposure to therapy with hormonal therapy has enabled the identification of specific genomic alterations that can promote resistance to hormonal therapy. This classification of genomic mechanisms of endocrine resistance has helped uncover the forces that shape the hormone dependence of ER+ breast cancer while also identifying new therapeutic targets with the promise to treat or even prevent endocrine resistant disease. In this presentation, we will review the genomic features of endocrine resistance metastatic breast cancer, detail evidence for (or against) specific alterations as likely mechanisms of resistance to endocrine therapy and describe next steps for clinical utilization of genomic information for the management of this disease.
Citation Format: P Razavi. The genomic landscape of endocrine-resistant metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES4-3.
Abstract ES5-2: Regional Management of the Axilla prior to Systemic Therapy
Authors: Pilewskie M 
Published: March 2020

Abstract
There is growing interest in personalizing axillary management strategies based on anatomic staging and receptor profile to minimize surgical morbidity and maximize oncologic outcomes. Axillary treatment decision making has become increasing complex given the variation in indications for axillary lymph node dissection (ALND) among clinically node negative patients based on treatment strategy. Current techniques to minimize the likelihood of requiring an ALND include application of the ACOSOG Z011 or AMAROS data for women undergoing surgery first or use of neoadjuvant chemotherapy (NAC) in attempts to downstage microscopic nodal disease. Hormone receptor positive, HER2 negative tumors have low pathologic complete response rates to NAC and therefore have low rates of axillary downstaging with this approach. We have evaluated the likelihood of requiring an ALND by receptor profile for differing management strategies. Given the low response rates to NAC among women with hormone receptor positive, HER2- tumors, use of NAC for this subtype is associated with a threefold increase in the receipt of ALND compared to those treated with upfront breast conserving surgery. In this session I will review the current strategies to minimize the likelihood of requiring an ALND among clinically node negative patients found to have a positive sentinel lymph node including application of the ACOSOG Z0011 and AMAROS strategies. I will also review the impact of axillary imaging and/or a positive lymph node needle biopsy on axillary surgery outcomes among clinically node negative patients. Having an understanding of these differing options will aid in personalizing axillary management recommendations to safely minimize the likelihood of ALND and the resultant risk of lymphedema.
Citation Format: M Pilewskie. Regional Management of the Axilla prior to Systemic Therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES5-2.
Abstract ES9-1: Discussing risk & uncertainty with patients in the context of GEP testing
Authors: Fallowfield L 
Published: March 2020

Abstract
Many discussions between physicians and their patients about the logic and rationale for different treatment recommendations are increasingly complex. The information required to aid educated decision-making requires careful balancing of the likely absolute benefits in terms of cure or preventing recurrence versus any treatment-related side effects. Few realise that medicine is an uncertain science where most facts are probabilities defined and refined by repeated hypothesis testing. In the context of life-threatening disease this can make communication with patients about risk and uncertainty challenging. Health literacy and numeracy skills in the general population are often poor, creating other communication difficulties; furthermore confusion increases when such conversations are set against a backdrop of fear and anxiety. Clinico-pathologic features traditionally help determine which women with early stage breast cancer are most likely to benefit from adjuvant chemotherapy, but many patients still believe that in life-threatening situations, more treatment must be better. Scores from gene expression profiling tests such as OncotypeDX®, EndoPredict® and Prosigna® may reduce some of the uncertainty and anxiety about omitting chemotherapy and increase the confidence of doctors helping patients with their decision-making.(1) However explaining high, intermediate and low risk test scores is not always straightforward especially when patients have widely varying personality and socio-educational characteristics. Both clinicians and their patients may also have a measurable intolerance to uncertainty that may contribute (irrespective of the recurrence score) to seemingly irrational decisions about treatment.
This interactive session will incorporate materials from Talking About Risk in the context of Genomic Testing (TARGET), an evidence-based program (2) funded by the BCRF- This includes didactic presentations (PPT) exercises and video clips of doctors explaining risk scores from genomic tests. After attending the session participants should:-
a) recognise how poor literacy and numeracy in general populations affects understanding about risk and decision-making b) understand how their own intolerance to uncertainty may ‘leak’ through into communication with patients and c) increase their repertoire of skills when explaining GEP scores to patients
References
1. L Fallowfield, L Matthews, S May, V Jenkins, D Bloomfield. Psycho-oncology (2018) 27:4, 1264-1269 https://doi.org/10.1002/pon.4664
2. Fallowfield, L., Solis-Trapala, I., Starkings, R. et al. Breast Cancer Res Treat (2019) 177: 641. https://doi.org/10.1007/s10549-019-05316-7
Citation Format: L Fallowfield. Discussing risk & uncertainty with patients in the context of GEP testing [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES9-1.
Abstract ES9-2: Communicating risk information: talking by numbers
Authors: Jenkins V 
Published: March 2020

Abstract
Health literacy and numeracy skills amongst the general population are frequently poor, which impedes their understanding of important health information. Even those patients fully conversant with percentages and ratios can suffer with math anxiety when involved in stressful environments, making it difficult to process complex information effectively. This may be especially true for women with breast cancer having to decide about adjuvant treatments after receiving risk of recurrence genomic expression profiling (GEP) test results. Explaining risk of recurrence clearly can be a challenge for the clinician and nurse too. They need a wide repertoire of communication skills to accommodate the needs of patients with different social and educational backgrounds. Some health care professionals (HCPs) use analogies to explain risk, which may not always be of benefit. In order to help HCPs discuss GEP test results we developed and evaluated an educational program called TARGET (Talking About Risk in the Context of GEnomic Tests). As part of the evaluation we measured participants’ own numeracy skills and intolerance to uncertainty. In this talk the audience will be invited to participate in various numeracy exercises, and be able to compare their results with UK data from 56 breast cancer clinicians and 78 specialist breast care nurses. The presentation will conclude with suggestions of different ways to communicate risk.
Citation Format: V Jenkins. Communicating risk information: talking by numbers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES9-2.
Abstract MS2-1: Mechanisms of resistance to CDK4/6 inhibitors and new therapeutic approaches
Authors: Chandarlapaty S 
Published: March 2020

Abstract
Activation of the CDK4/6 kinases is a well-established mechanism whereby estrogens and other mitogens drive breast cancer growth. ATP competitive inhibitors of the CDK4/6 kinases have had a transformational impact on the clinical approach to ER+ breast cancer patients. However, with prolonged CDK4/6i therapy, most tumors ultimately develop resistance. Unlike the case for acquired resistance to many other targeted therapies, CDK4/6i resistance does not appear to be occur through mutations of the drug target. Second site, missense mutations in CDK4 and CDK6 have not been identified in either preclinical resistance screens or clinical biopsies of resistant tumors. This raises several questions including: (1) what are the genetic alterations and pathways that mediate resistance to CDK4/6i therapy in breast cancer, (2) what therapeutic approaches are effective after tumors have developed resistance to CDK4/6i, and (3) what can these understandings about resistance teach us about the underlying basis for sensitivity to CDK4/6i therapy. In this talk, published and unpublished data on mechanisms of resistance to CDK4/6i will be reviewed to elucidate how tumors can either restore CDK4/6 activity or else bypass the requirement for these G1 checkpoint kinases. Data on potential vulnerabilities for each class of drug-resistant tumors will then be discussed. Finally, the findings on resistance will be used to revisit the original understandings on the basis for CDK4/6i sensitivity and how that informs the ongoing use of these drugs in other settings and with more effective combinations that might suppress the emergence of resistance.
Citation Format: S Chandarlapaty. Mechanisms of resistance to CDK4/6 inhibitors and new therapeutic approaches [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr MS2-1.
Abstract OI: Novel non-canonical functions of EZH2 in triple negative breast cancer
Authors: Kleer CG 
Published: March 2020

Abstract
Patients with distant metastasis at the time of diagnosis have significantly worse prognosis. Triple negative breast carcinomas (TNBC) are heterogeneous tumors with propensity to metastasize and a guarded short term prognosis. The link between breast cancer and regulators of cell type identity was demonstrated in 2003, when enhancer of zeste homolog 2, EZH2, was reportedly overexpressed in approximately 55% of breast cancer tissue samples and was significantly associated with estrogen receptor negative status and worse disease free and overall survival. As the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), the methyltransferase EZH2 deposits trimethyl marks on histone tails of lysine 27 of histone H3 (H3K27me3) to effect transcriptional repression. However, in a subset (~ 30%) TNBC high levels of EZH2 are associated with low H3K27me3, suggesting the intriguing possibility that in this group of tumors EZH2 may promote progression through other unknown mechanisms. Recent studies have shown that in TNBC EZH2 may indeed function independent of PRC2 and H3K27me3 activity. During breast cancer initiation, EZH2 enhances breast cancer stem cells and mammary tumor development through transcriptional activation of NOTCH1 and upregulation of its signaling pathway. More recent data show that EZH2 protein binds to p38 MAP kinase with resulting EZH2 phosphorylation at threonine 367 and accumulation in the cytoplasm of TNBC cells. In breast cancer tissue samples, cytoplasmic pEZH2 T367 is significantly associated with low H3K27me3 levels and a triple negative phenotype. Mechanistically, pEZH2 T367 protein binds to cytoplasmic regulators of cell migration and invasion, and is required for metastasis. These studies demonstrate a H3K27me3-independent mechanism of EZH2 function in TNBC progression. Future investigations will be required to test the therapeutic potential of inhibiting EZH2 non-canonical mechanisms alone or in combination with pharmacological targeting of EZH2 methyltransferase activity in TNBC.
Citation Format: CG Kleer. Novel non-canonical functions of EZH2 in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OI.