bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-10-04: Exome sequencing in high breast and ovarian cancer incidence families which lack detectable mutations in established cancer susceptibility genes
Authors: Kenny PA , Girtman MA , Deviley JA , Meier DR , Vos CR , Richmond CS , Lofgren KA 
Published: May 2019

Abstract
At our center, a standard 25 gene panel has proved useful for the identification of pathogenic germline mutations in many families with a high penetrance of breast and ovarian cancer, yet there remain several families with very high cancer incidence but from whom these assays have not identified pathogenic alleles. To attempt to define the genetic mechanism of susceptibility in such cases, are conducting germline whole exome sequencing in affected individuals. Here we describe the identification of strong candidate susceptibility variants in two such families. Both variants cause loss-of-function of DNA repair genes not previously implicated in breast cancer, but which share properties with genes with known roles in maintenance of genome integrity. In one individual, with a personal history of ovarian cancer and two independent breast tumors, we identified a novel point mutation in POLD2 which introduces a mutation at a residue which is biochemically conserved in all animal species thus far sequenced. In the second individual, a frameshift mutation was detected in ERCC4. In both cases, the variants found have not been observed in large exome datasets (e.g. ExAC) or reported in ClinVar. Our study highlights the potential utility of whole exome sequencing as a discovery tool in those families with high cancer incidence yet which lack mutations in known hereditary cancer predisposition genes.
Citation Format: Kenny PA, Girtman MA, Deviley JA, Meier DR, Vos CR, Richmond CS, Lofgren KA. Exome sequencing in high breast and ovarian cancer incidence families which lack detectable mutations in established cancer susceptibility genes [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 P5-10-04.
Abstract P5-11-08: Genetic landscape of prior and resistance to CDK4/6 inhibition in targeted NGS panel analysis of palbociclib or abemaciclib and endocrine versus placebo and endocrine
Authors: Xu J , Sun T , Wang X 
Published: May 2019

Abstract
Background: CDK4/6 inhibition combined with endocrine therapy is now a standard of care for advanced estrogen receptor (ER) positive breast cancer. Predictive genetic landscape and mechanisms of resistance to CDK4/6 inhibitors have not been described clearly because of limited evidence from clinical samples. We investigated the genetic landscape and mechanisms of resistance to CDK4/6 inhibitors (palbociclib or abemaciclib).
Methods: Using driver mutation targeted sequencing, we conducted longitudinal ctDNA analysis in 39 pairs of baseline of primary tumor and end of treatment or monitoring plasma samples. DNA were extracted and the genomic profiles were analyzed based on NGS.
Results: In our cohort, the most frequence mutations were PIK3CA (38.5%), TP53(17.9%), CCND1, ZNF703, FGFR1, MAP2K4, RB1, ARID1A, ATRX, DNMT3A. In five paitents harboring RB1 mutations prior to CDK4/6 inhibitor, only one case occured progressing early with 4mos of PFS, and the others were 5.5+, 6.5+, 13.5+, 21+months, it represented different from pre-clinical results that RB1 mutation was associated with resistance to CDK4/6 inhibitor. Interesting, patients with PIK3CA/PTEN/AKT1 mutations (n=15) were likely sensitivity to CDK4/6 inhibitor than those (n=11) with wild type (median PFS: 17 mos vs. 9.5mos, P=0.046). In another cohort of everolimus, new driver mutations emerged in both FGFR1 and ERBB3 at end of everolimus and significantly disappeared in AKT1 mutation. Three patients used palbociclib after progress disease of everolimus, the prognosis were poor with PFS of 1, 6, 9 mos. Evolution of driver gene mutations was uncommon in patients progressing on CDK4/6 inhibitors treatment, but common in patients progressing on everolimus treatment.
Conclusions: De novo PIK3CA/PTEN/AKT1 mutations were likely better prognosis biomarkers with the treatment of CDK4/6 inhibitor. RB1 mutation are common and may not contribute to CDK4/6 inhibitor resistance differ from PALOMA3 ctDNA analysis. Our small sample finding indicate it may be a bad stragegy for CDK4/6 inhibitor after progress disease with mTOR inhibitor everolimus.
Citation Format: Xu J, Sun T, Wang X. Genetic landscape of prior and resistance to CDK4/6 inhibition in targeted NGS panel analysis of palbociclib or abemaciclib and endocrine versus placebo and endocrine [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 P5-11-08.
Abstract P5-13-02: Not presented
Authors: Rositch AF , Ginsburg OM , Huang L , Chao CA , Visvanathan K , Masalu N 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Rositch AF, Ginsburg OM, Huang L, Chao CA, Visvanathan K, Masalu N. Not presented [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 P5-13-02.
Abstract P5-13-09: Not presented
Authors: Campos-Gomez S , Pacheco-Cuéllar G , Campos-Gomez K , García Garcés M , Valdes Andrade J , Barrera Franco JL 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Campos-Gomez S, Pacheco-Cuéllar G, Campos-Gomez K, García Garcés M, Valdes Andrade J, Barrera Franco JL. Not presented [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 P5-13-09.
Abstract P5-13-21: The European initiative in breast cancer (ECIBC) - A program to reduce disparities in cancer care by accreditation of all breast centers in Europe
Authors: Mansel RE 
Published: May 2019

Abstract
In order to reduce disparities in breast cancer services in Europe, the European Parliament passed resolutions in 2003 and 2006 calling for all women with breast cancer in Europe to be treated by a multidisciplinary team and called on Member States to establish a network of Certified multidisciplinary breast centres.
In the light of these resolutions the European Commission has tasked the Joint Research Centre (JRC) based in Ispra in Italy to set a programme of work from 2014-2020 to update the European Screening Guidelines and produce standards for an accreditation programme for all European Member States.
The methodology is evidence based and the Ibero American Cochrane group has been recruited to examine the evidence for the key questions concerning quality indicators. The whole pathway for breast cancer treatment is being explored from screening to follow up/survivorship, and only indicators supported by evidence are accepted. Indicators have to be relevant, measurable and feasible and currently 50 indicators have been approved using the Delphi system. Many currently used indicators have failed the test of usability due to lack of precision in measurement (eg cosmetic outcomes, margin assessment), or lack of clear definitions (eg counselling,breast care nurse roles, waiting times, MDT working).
A further problem is the different resources applied to breast services across the wide range of economies in European countries (Western v Eastern Europe), which affects the availability of expensive therapies.
The Indicators will form the basis of the accreditation program which will be published in 2019. The detailed evidence for each indicator will be presented in the poster together with the feedback from the 30+European countries involved.
A pilot of the accreditation program will take place in 2019 to test the feasibility of the audit process in a variety of breast clinic settings.
This project is the most comprehensive attempt to date to produce a robust measurement of breast centers performance based on evidence, and might have global applicability.
Citation Format: Mansel RE. The European initiative in breast cancer (ECIBC) - A program to reduce disparities in cancer care by accreditation of all breast centers in Europe [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 P5-13-21.
Abstract P5-14-03: Patient perspectives on HER2+ breast cancer recurrence: Results from an online patient survey
Authors: Jenkins M 
Published: May 2019

Abstract
Background: The objective of this study was to gather insights from patients with early-stage HER2+ breast cancer regarding fears and knowledge of breast cancer recurrence and approaches to reducing risk of recurrence.
Methods: From Nov. 7-30, 2017, patients with stage I-IIIC HER2+ breast cancer were recruited via postings to Breastcancer.org discussion boards to participate in an online survey comprising 17 questions designed to quantify fears and emotions related to recurrence, identify and characterize knowledge gaps, and understand what patients are willing to tolerate to reduce recurrence risk.
Results: Of 307 respondents, 87% were aged ≥40 years and over half were ≥50 (58%). The majority had completed (48%) or were undergoing (39%) postsurgical treatment. Recurrence was a concern for 93% of patients and was the highest rated concern for 78%; however, most patients (76%) perceived their personal risk of recurrence to be moderate or low. 59% of patients felt they were at least somewhat informed about risk of recurrence; 55% had discussed risk of recurrence with their health care team, with discussions most frequently initiated by the patient (56%) vs the health care team (40%). Oncologists were the primary source of information about risk of recurrence (58%), but patients also frequently sourced information from online content (29%), published research (18%), and Breastcancer.org (15%). Almost all (96%) patients were at least somewhat involved in treatment planning. While 55% of patients would inquire about a new drug if it conferred a 10%-20% reduction in risk of recurrence, 26% required a benefit of ≥50%. For treatments reducing the risk of recurrence, patients were willing to tolerate (in order from most to least willing) hot flashes, fatigue, diarrhea, joint pain, and nausea/vomiting.
Conclusions: While patients with HER2+ breast cancer are highly concerned about recurrence, most feel that their personal risk is moderate. Patients are highly engaged in treatment planning, often initiate discussions about risk of recurrence, and supplement their knowledge with their own research. The threshold to motivate inquiry into a new drug to reduce recurrence risk was &lt;20% for over half of patients. Patients were also frequently willing to tolerate common adverse events.
Citation Format: Jenkins M. Patient perspectives on HER2+ breast cancer recurrence: Results from an online patient survey [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 P5-14-03.
Abstract P5-15-07: Breast surgery – Is routine 'group & save' required? A quality improvement project
Authors: Burrah R , Chicken W , Sathananthan S 
Published: May 2019

Abstract
Introduction
Breast surgery, especially for malignant disease, is not associated with significant blood loss and therefore rarely requires blood transfusions. Pre-operative protocols in our hospital and in most other centers routinely require a blood group screening process (group and save) for elective breast cancer surgery. The process of group and save (G&S) in our hospital requires two blood samples to be drawn with at least 30 minute interval in-between. It takes at least 40 minutes for the samples to get processed and the cost for each test is £2.12. The test is valid for a period of 5 days after which time it needs to be repeated. This process in busy hospitals is clearly time consuming, results in delays and is inconvenient for patients and medical staff.
The aim of this study was to ascertain the number G&S performed and rate of post-operative blood transfusion for patients undergoing surgery for malignant breast disease. This was to establish if mandatory pre-operative G&S is necessary in all cases, and if the number of tests performed can be reduced. The second part of the study was to analyze the outcome after implementation of changes to reduce the number of G&S tests.
Method
Retrospective review of patient records who had surgeries for malignant breast disease from December 2015 to November 2016. Exclusion criteria included benign disease, flap reconstruction and breast surgery combined with another major procedure. Following the initial analysis, it was proposed that only the operating surgeon will request the test and that it will not be routinely requested by the pre-op assessment team. A re-audit was done prospectively to study the outcome of change in practice and close the audit loop.
Results
151 cases were eligible for review. 97.35% (147 patients) had G&S, and the post-operative transfusion rate was 1.32% (2 patients). Following a change in protocol a significant fall in the testing (97.35% to 35.5%) was seen and there were no post-operative blood transfusions in this period.
Conclusion
This simple yet important audit showed that routine G&S did not contribute to the patient management, increased cost of treatment, caused patient inconvenience and consumed hospital personal time. The changes we implemented significantly reduced the frequency of this test and was cost effective to the trust. This study has now been converted into a Quality Improvement Project and through this we will continue to improve the results further. This project has also stimulated an interest in the General Surgery department, and other units are now considering changing their practice based on our results.
Citation Format: Burrah R, Chicken W, Sathananthan S. Breast surgery – Is routine 'group & save' required? A quality improvement project [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 P5-15-07.
Abstract P5-18-09: Performance of Oncotype DX DCIS score across diverse ethnic populations
Authors: Mittar P , Casella S , Bombonati A , Emiloju O , Jablon L , Schultz D , Leighton JC , Solin LJ 
Published: May 2019

Abstract
There is a paucity of data on Oncotype DX DCIS Score and ethnic variation. It has been postulated that there are different molecular features /drivers among different ethnic populations. The Oncotype DX DCIS Score is a genomic test designed to analyze the expression of a group of 12 genes which can quantify 10-year local recurrence risk after surgery. The purpose of this study is to evaluate diverse ethnic patients with DCIS relative to traditional clinical pathologic factors and Oncotype DX DCIS Score
We analyzed consecutive cases of DCIS from 2011-2017 who underwent Oncotype DX DCIS Score testing at a single institution. Eighty-four female patients were divided into 5 groups based on self-reported ethnicity: White (36%), African American (AA) (48%), Asian (8%), Hispanic (4%) and Other (4%). Clinical and traditional pathologic factors were collected including age, nuclear grade (NG), ER/PR status and Oncotype DX DCIS Score. The distribution of NG and Oncotype DX DCIS Score was analyzed across ethnic groups.
The mean age at diagnosis was 63. Overall 99 % of cases were hormone positive. Comparison of White and AA patients revealed a correlation between ethnic group and DCIS Score, with a p value of 0.0087 (Table 1). Similarly, we looked at all five ethnic groups and Oncotype DX DCIS Score and found a p value of 0.022. We evaluated ethnicity with White and AA patients versus NG and obtained a p value of 0.084 (Table 2). In addition, we assessed all five ethnic groups and NG. We obtained a p value of 0.068. No AA patients with DCIS had a high DCIS Score. No patients with low NG DCIS had a high DCIS Score. Analysis of the three factors (NG, ethnicity and DCIS Score) concurrently showed that they are not independent.
In summary, our study provides valuable data on Oncotype DX DCIS Score and NG across a diverse patient population. These data highlight the importance of incorporating both traditional clinical pathologic factors and DCIS Score molecular testing for making treatment decision across different ethnic patient populations.
Table 1.Comparison of DCIS Score and Ethnic GroupEthnic GroupLow DCIS ScoreIntermediate DCIS ScoreHigh DCIS ScoreAA3730White2704p=0.0087
Table 2.Comparison of Nuclear Grade and Ethnic GroupEthnic GroupNuclear Grade 1Nuclear Grade 2Nuclear Grade 3AA17194White1399p=0.084
Citation Format: Mittar P, Casella S, Bombonati A, Emiloju O, Jablon L, Schultz D, Leighton JC, Solin LJ. Performance of Oncotype DX DCIS score across diverse ethnic 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 P5-18-09.
Abstract P6-02-14: Not presented
Authors: Xing W , Li Q , Sun G , Cao R , Chen B , Jiang C , Ma L , Wang K 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Xing W, Li Q, Sun G, Cao R, Chen B, Jiang C, Ma L, Wang K. Not presented [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 P6-02-14.
Abstract P6-02-19: Machine learning based analysis of CT radiomics for the simultaneous indeterminate pulmonary nodules of breast cancer
Authors: Xiao Q , Gu Y , Wu J , Wang Z , Huang Y 
Published: May 2019

Abstract
PURPOSE: To investigate texture features of simultaneous indeterminate pulmonary nodules of breast cancer for predicting their potential metastasis.
METHODS AND MATERIALS: 150 patients with simultaneous breast cancer diagnosed by biopsy and pulmonary nodules (diameter: 5-20mm) detected by preoperative CT were enrolled in this study. After surgery and breast cancer treatment, the patients were followed up for at least half a year or longer by CT to observe the changes of lung nodules, thereby inferring the potential of metastasis. We classify pulmonary nodules into two groups: the reduced or enlarged pulmonary nodules were defined as highly metastasis possibility (Group 1), and long-term stable pulmonary nodules were defined as low metastasis possibility (Group 2). In addition, pathologic proven primary lung cancer in this study (Group 3) was compared with Group 1. Therefore, we carried out a comparative analysis of the texture features between the groups, and additional statistical were used three regression testing to extract texture features. Finally, we construct a machine learning classifier and calculate the accuracy of cross-validation.
RESULTS: We collected 106 features by the texture analysis(TA). There are 18 features with significant differences between Group 1 and the Group 2(p&lt;0.05), and 76 features with significant differences in the Group 1 and Group 3 (p&lt;0.05). We tried to find key features related to pathology in 106 features using three methods: lasso regression, ridge regression and forward stepwise regression. The accuracy in different regressions respectively is 94.5%,94.5%,89.7% using KNN between Group 1 and Group 2. The accuracy in different regressions respectively is 96.2%(KNN),96.2%(Tree),92.3%(Linear Discriminant)in the Group 1 and Group 3.
CONCLUDES: The identified radiomics features have the potential to be used as a biomarker for metastasis prediction of simultaneous indeterminate pulmonary nodules in breast cancer patients, and it may contribute to preoperative treatment and postoperative follow-up planning.
Citation Format: Xiao Q, Gu Y, Wu J, Wang Z, Huang Y. Machine learning based analysis of CT radiomics for the simultaneous indeterminate pulmonary nodules of 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 P6-02-19.
Abstract P6-03-06: Androgen supplementation in patient derived xenografts in androgen receptor positive breast cancer to increase engraftment and growth rate
Authors: Kiver VII , Wulf-Goldenberg A , Jurmeister PS , Schweiger C , Gorea O , Hoffmann J , Denkert C , Keilholz U , Liedtke C , Blohmer J-U 
Published: May 2019

Abstract
Background:
The European fund for regional development (EFRE) supported Precision Oncology and Personalized Therapy Prediction (POP) Project is establishing preclinical models to further the development of personalized therapy options. In the subgroup breast cancer the current goal is to increase the growth and engraftment rates of breast cancer patient derived xenografts (PDX) models.
Methods:
Breast cancer patients of the Department of Gynecology with Breast Center Charité Universitätsmedizin Berlin, Germany are recruited since May 2017. In total 29 tissue samples were collected and included so far.
Treatment naive and treatment refractory patients, tripple negative breast cancer (TNBC), hormone receptor positive (HR+) and Her2 postivie tumors, primary disease, recurrence or metastasis are sampled. Fresh tumor tissue is extracted via surgery or biopsy. The materials are then implanted into female immunodeficient NOG mice. To establish PDX models for HR+ breast cancer the mice received estrogen supplementation.
To increase engraftment and growth rates androgen receptor (AR) testing and subsequently androgen replacement was started since April 2018.
Up to date, 6 new samples have been collected. One HR+ and two TNBC samples tested also positive for AR. These samples are currently in passage 0 (p0) and are now supplied with androgens to increase engraftment and growth rate. One already established AR+ TNBC PDX is being regrown with androgen supplementation to compare growth rates.
Results:
Out of the initial 23 tissue samples ten (six HR+ and four TNBC) have been able to be engrafted into PDX mice.
The TNBC PDX models are one in p1, one in p2, one in p3 and one is being tested with systemic therapy. Engraftment time in p1 were between 19 and 97 days. Growth time to passagable size between 21 and 112 days.
The HR+ PDX models are four in p1 and two in p2. Engraftment time in p1 was between 26 and 123 days. Growth time to passagable size has been achieved in 2 HR+ PDX within 17 to 48 days.
The engraftment/growth rates and times of the androgen supplemented PDX models will be presented.
Conclusion:
Breast cancer growths in humans slowly and this is also the case in the PDX models. To achieve faster growth and higher engraftment rates androgen supplementation in AR+ breast cancer might be an additional enhancive factor.
Citation Format: Kiver VII, Wulf-Goldenberg A, Jurmeister PS, Schweiger C, Gorea O, Hoffmann J, Denkert C, Keilholz U, Liedtke C, Blohmer J-U. Androgen supplementation in patient derived xenografts in androgen receptor positive breast cancer to increase engraftment and growth rate [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 P6-03-06.