bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-09-16: Multiple mutations in a single lineage: is it time for a shift in predictive testing?
Authors: Scalia Wilbur J , Laprise J , Beaston M , Legare RD 
Published: May 2019

Abstract
Germline cancer genetic testing is a critical part of patient care influencing cancer risk reduction, prevention and now treatment decision-making. Single syndrome and mutation testing has been available for twenty years, however massively parallel sequencing technology has made multigene panel tests more readily available and at lower costs. Currently, it remains unclear if there is benefit related to panel testing in cancer families and patients already harboring a pathogenic mutation. We report 5 families found to harbor additional pathogenic mutations identified with multigene panel testing.
One Ashkenazi family was found to harbor both a founder and non-founder BRCA mutation in a single lineage. Four additional families were found to harbor a second mutation in either a novel breast/ovary cancer gene or in a gene related to an established cancer syndrome. All patients were either initially BRCA2 or PALB2 positive and were subsequently found to have a second mutation in either CHEK2, RAD51D, ATM, MUTYH or PMS2. In 2 cases, the secondary mutation either increased frequency and/or decreased start age of colonoscopy screening. Interestingly, 2 of the additional mutations were first reported as variants of uncertain significance later reclassified as likely pathogenic.
In all cases the traditional approach of single site/syndrome analysis for predictive testing would have failed to identify the second pathogenic mutation resulting in an underestimate of cancer risk in negative family members. Notably, the majority of secondary mutations were present within the same lineage as the known familial mutation. In 3 of 5 cases, the finding of a second mutation in already identified mutation carriers led to additional changes in medical management. As multigene panel testing becomes more accessible in both cost and provider acceptance, this case series illustrates the need to strongly consider use of multigene panel testing for relatives undergoing testing for known familial mutations regardless of family history, and ultimately indicating a role for re-testing established mutation carriers.
Citation Format: Scalia Wilbur J, Laprise J, Beaston M, Legare RD. Multiple mutations in a single lineage: is it time for a shift in predictive testing? [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 P5-09-16.
Abstract P5-09-18: Multiple cancer susceptible genes sequencing in BRCA-negative breast cancers with high hereditary risk
Authors: Lang G-T , Hu X , Shi J-X , Huang W , Shao Z-M 
Published: May 2019

Abstract
Background Breast cancer susceptibility is strongly associated with a patient's hereditary background. Comprehensive BRCA mutation screening in our cancer center shows a lower BRCA mutation prevalence (9.1%) in Chinese breast cancer patients with hereditary risk. Multiple cancer susceptible genes sequencing can assist in discovering detrimental germline mutation in BRCA-negative breast cancers.
Methods From 2005-2014, BRCA-negative breast cancer patients with any two of the following risk factors were recruited: (1) pathological diagnosis of triple-negative breast cancer, (2) male breast cancer, (3) primary bilateral breast cancers in one individual, regardless of synchrony or asynchrony, (4) early-age onset breast cancer (less than or equal to 40 years of age at diagnosis), or (5) patients with a family history of breast and/or ovarian cancer (at least one first- and/or second-degree relative with breast cancer or ovarian cancer). A total of 384 Chinese subjects were screened by next-generation sequencing for 32 breast cancer associated susceptibility genes (APC, ATM, BARD1, BMPR1A, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MEN1, MET, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PALLD, PMS2, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RET, SMAD4, STK11, TP53, VHL). Mutations were classified as pathogenic/likely-pathogenic if they had a truncating, initiation codon or splice donor/acceptor effect, or if pathogenicity was demonstrated in published literature.
Results In total, we acquired 39 patients (10.2%) with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11), PTCH1 (n=7), RET (n=6) and PALB2 (n=5). Other mutant genes included TP53 (n=3), RAD51D (n=2), CHEK2 (n=1), BRIP1 (n=1), CDH1 (n=1), MRE11 (n=1), RAD50 (n=1) and PALLD (n=1). In addition, PTCH1 mutation carriers were found to be associated with the clinical features of triple-negative and early-age onset breast cancer.
Conclusions Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in breast cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Some clinical features might be associated with germline mutations of particular genes in breast cancer.
Key words germline mutation, BRCA-negative, hereditary breast cancer, multiple-gene sequencing
Citation Format: Lang G-T, Hu X, Shi J-X, Huang W, Shao Z-M. Multiple cancer susceptible genes sequencing in BRCA-negative breast cancers with high hereditary 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 P5-09-18.
Abstract P5-10-05: Not presented
Authors: Semetei Kyzy A , Makimbetov E , Kudaibergenova I , Isakova J 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Semetei Kyzy A, Makimbetov E, Kudaibergenova I, Isakova J. 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 P5-10-05.
Abstract P5-11-11: A preliminary assessment of knowledge, attitudes, and awareness surrounding ESR1 mutations and biomarker testing amongst medical oncologists
Authors: Goldfarb SB , Goetz MP , Plourde PP , Attias E , Portman DJ 
Published: May 2019

Abstract
Background: Estrogen receptor gene (ESR1) mutations present in breast cancer patients are associated with resistance to endocrine therapy and worse patient outcomes. Recent findings suggest ESR1 mutations are present in up to 40% of metastatic breast cancer (mBC) patients' tumors. The objective of this study was to evaluate the perceptions of precision medicine and biomarker testing specific to ESR1 mutations among medical oncologists.
Methods: Ten 60-minute web-assisted, telephone interviews were conducted with medical oncologists. Each physician was prescreened prior to being interviewed to ensure board certification and practice experience between 2 and 35 years. Each participant spent greater than 30% of their time on direct patient care and managed the treatment of more than 30 different cancer patients per month, with a minimum of 15 breast cancer patients, including at least five who had metastatic breast cancer and at least one patient with an ESR1 mutation.
Results: A 10-20% prevalence of ESR1 mutation was estimated by the oncologists. However, the practitioners did accept the possibility of a 40% prevalence. Physician knowledge of ESR1 mutations included the relationship between ESR1 mutations and efficacy of endocrine therapies and its association with poorer outcomes. None of the medical oncologists interviewed were highly satisfied with the existing armamentarium of treatments for patients with an ESR1 mutation.
In general, the interview participants were highly comfortable ordering ESR1 companion diagnostics to test for an ESR1 mutation, pending viable treatment options are available. Nonetheless, most physicians will wait until the patient has progression of disease before ordering a biomarker test. Several areas of unmet need in the mBC arena were offered by the survey participants, including more efficacious hormonal options for later-line therapies, better durability of remission, improved drug tolerability profiles, and lower treatment costs.
Conclusion: Most oncologists acknowledged that personalized treatment is beneficial because it allows for better efficacy than a “one size fits all” approach. The study results also suggest that there are few barriers and drawbacks to the use of personalized medicine in the mBC arena, as most physicians expect precision medicine to account for the majority of advances in breast cancer treatments in the foreseeable future.
Support: Sermonix Pharmaceuticals
Citation Format: Goldfarb SB, Goetz MP, Plourde PP, Attias E, Portman DJ. A preliminary assessment of knowledge, attitudes, and awareness surrounding ESR1 mutations and biomarker testing amongst medical oncologists [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 P5-11-11.
Abstract P5-12-12: ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 breast cancer patients
Authors: Győrffy B , Fekete J 
Published: May 2019

Abstract
Prognostic biomarkers are capable to predict survival and predictive biomarkers are capable to predict therapy response. Systemic therapy of breast cancer can include chemotherapy, hormonal therapy, and targeted therapy. Here, we report the initial release of the first online available tool capable to identify gene expression based predictive biomarkers using transcriptomic data of a large set of breast cancer patients.
Published gene expression data of 44 publicly available datasets was integrated with treatment data into a unified database. The classification is based on either author-reported pathological complete response (n=1,775) or relapse-free survival status at five years (n=1,329). Treatment data includes chemotherapy (n=2,108), endocrine therapy (n=971), and anti-HER2 therapy (n=267). The transcriptomic database includes 20,089 unique genes and 54,675 probe sets. Gene expression and therapy response are compared using receiver operating characteristics and Mann-Whitney tests.
We demonstrate the utility of the tool by validating a set of established biomarkers including TP53 for chemotherapy in luminal breast cancer (p=5.2e-20, AUC=0.77), ERBB2 for trastuzumab therapy (p=8.4e-04, AUC=0.629), and PGR for hormonal therapy (p=8.6e-05, AUC=0.7).
The tool is designed to validate and rank new predictive biomarker candidates in real time. By analyzing the selected genes in a large set of independent patients, one can select the most robust candidate and quickly eliminate those which are most likely to fail in a clinical setting. The analysis tool is accessible at www.rocplot.org/breast.
Citation Format: Győrffy B, Fekete J. ROCplot.org: validating predictive biomarkers of response to chemotherapy/hormonal therapy/anti-HER2 therapy using transcriptomic data of 3,150 breast cancer 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 P5-12-12.
Abstract P5-12-13: Changing level of serum heat shock protein 90 alpha as a diagnostic and predictive marker in breast cancer: Diagnosis of early breast cancer and prediction of response to neo-adjuvant and surgical therapy
Authors: Hu N , Li M , Zhu A , Du F , Yuan P 
Published: May 2019

Abstract
To analyze the correlation of the level of serum heat shock protein 90α (HSP-90α) in healthy and breast cancer patients, studying the evaluation of neoadjuvant efficacy and Clinical value of relapse monitoring.
A total of 102 healthy women were selected, 51 cases of breast benign tumor ,423 cases of female breast cancer all diagnosed by pathology,other system malignancies 62 cases. ALL the serum samples HSP-90αwas detected by double-antibody ELISA. The CEA, CA125,CA15-3 were detected by Roche Cobas ECL analyzer. The ROC curve was used to analyze the effectiveness of serum HSP-90α in the early diagnosis of breast cancer. The dynamic changes of HSP-90αlevel before and after treatment were analyzed by Wilcoxon's rank test. Moreover, we also combine the HSP-90αwith CEA,CA125,CA15-3 to evaluate the clinical value of monitoring the recurrence of breast cancer.
The levels of serum HSP-90α (123.49 ± 105.1ng / ml) in breast cancer patients wes significantly higher than that in healthy controls (40.33 ± 14.18ng / ml), benign breast disease (80.15 ± 103.09ng / ml) and carcinoma in situ (34.7 ± (114.31 ± 146.91ng / ml),the difference was statistically significant (P &lt;0.001). .According to the ROC curve analysis of patients and healthy subjects, the cut-offvalue was set as HSP-90=59.7ng / ml, AUC=0.834, the sensitivity and specificity to diagnosis of breast cancer was 90.3% and 78.6% respectively ,the negative predictive value was 93.88%.The levels of serum HSP-90α was significantly decreased (P &lt;0.05) after tumor resection and the patients who obtain PR from the neoadjuvant chemotherapy. When HSP-90=43.22ng / ml was set as the cut-off value for diagnosing the recurrence of breast cancer, AUC=0.877,the sensitivity and specificity were 95.7% and 74.5% respectively, and the negative predictive value was 96.2%. At the same time, we find that combined HSP-90α with CEA, CA125, CA15-3 can improve the accuracy of recurrence prediction.
Serum HSP-90α has a good clinical diagnostic value in breast cancer and can be used as a recurrence monitoring tool for post-adjuvant treatment patients.
Citation Format: Hu N, Li M, Zhu A, Du F, Yuan P. Changing level of serum heat shock protein 90 alpha as a diagnostic and predictive marker in breast cancer: Diagnosis of early breast cancer and prediction of response to neo-adjuvant and surgical therapy [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 P5-12-13.
Abstract P5-14-02: Time to treatment discontinuation as a pragmatic endpoint: A U.S. Food and Drug Administration pooled analysis of CDK 4/6 inhibitors
Authors: Gao JJ , Gong Y , Cheng J , Schroeder RJ , Amiri-Kordestani L , Khozin S , Kluetz P , Sridhara R , Pazdur R , Blumenthal G , Beaver JA , Prowell TM 
Published: May 2019

Abstract
BACKGROUND: The primary endpoint in many registration trials is progression-free survival (PFS), defined as the time from randomization until objective tumor progression or death. In the clinical setting, however, PFS can be difficult to measure and explain, especially in patient-friendly language. For real-world evidence (RWE) based studies, time to treatment discontinuation (TTD), defined as time from randomization to discontinuation of the investigational study drug, may be a more practical endpoint. We hypothesize TTD will correlate with PFS and analyzed registration trials from recently FDA approved cyclin dependent kinase 4/6 inhibitors (CDKIs) to test this hypothesis. TTD was defined as time from randomization to discontinuation of the CDKI.
METHODS: We pooled data from five phase III randomized, controlled, registration trials of CDKIs with an aromatase inhibitor (AI) in the first-line or fulvestrant in the second-line setting. The CDKI discontinuation dates used to calculate TTD were derived from the patient-level datasets. We calculated patient-level correlation between TTD and PFS. We also summarized median TTD and PFS as well as the number of TTD and PFS events.
RESULTS: A total of 3017 patients were included in the pooled analysis (n=1899 treated with CDKI, n=1118 with placebo). The median PFS and TTD and the number of events are shown in Table 1. The patient-level Spearman correlation coefficient of TTD and PFS ranged from 0.87-0.95. The trial-level association was approximately R2=0.23.
Table 1:Primary ResultsTreatment ArmNPFS EventsTTD EventsMedian PFS, in mo (95% CI)Median TTD, in mo (95% CI)Spearman Correlation CoefficientCDKI1899873138320.7 (19.2-22.2)14.3 (13.6-14.9)0.87Placebo111871488311.7 (11.0-13.6)11.0 (9.7-12.0)0.95
CONCLUSION: Patient-level pooled cross-trial analysis show a relationship between TTD and PFS in registration trials of CDKIs. In all trials, the difference in time between median TTD and median PFS appeared greater in the CDKI arm than the placebo arm. This analysis is limited by the relatively small number of studies included. Further research is needed to determine both whether: 1) TTD can serve as a pragmatic endpoint for analyses of RWE, and 2) is a more meaningful endpoint to patients.
Citation Format: Gao JJ, Gong Y, Cheng J, Schroeder RJ, Amiri-Kordestani L, Khozin S, Kluetz P, Sridhara R, Pazdur R, Blumenthal G, Beaver JA, Prowell TM. Time to treatment discontinuation as a pragmatic endpoint: A U.S. Food and Drug Administration pooled analysis of CDK 4/6 inhibitors [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 P5-14-02.
Abstract P5-14-09: Integration of primary care practitioners in a breast multidisciplinary team meeting- A pilot study
Authors: Pitcher ME , Hornung I , Rangarajan P 
Published: May 2019

Abstract
Primary care practitioners are key to integrated patient care, as they often have an established relationship with patient and family, with knowledge of comorbidities and psychosocial factors. They can encourage compliance with cancer treatments and manage transition from acute care through survivorship.
Communication with primary care however has often been unsatisfactory, with information not helpful to that practitioner or not provided in a timely manner.
We recruited a general practitioner (GP) to attend the weekly breast cancer multidisciplinary meeting, with a responsibility to make contact with the primary care practitioner of patients presented prior to the meeting, so that relevant information from a primary care perspective could be taken into consideration for team deliberations. This also meant that the primary doctor was aware the patient was being discussed. Recommendations were fed back to that doctor after the meeting so that information was timely, and, being given by a peer, more useful.
The GP attended 12 consecutive MDTs where 105 patients were discussed. In 55% contact was able to be made with the patient's GP prior to the meeting. This was perceived as not usually changing management plans, but reinforced known medical and social concerns. Feedback to the patients GP was regarded favourably, with reported greater confidence in managing the patient, particularly those with complex needs, as well as improving hospital to community communication in general.
This pilot has shown that it is feasible to include primary care practitioners in a multidisciplinary meeting and improve interdisciplinary communication.
Citation Format: Pitcher ME, Hornung I, Rangarajan P. Integration of primary care practitioners in a breast multidisciplinary team meeting- A pilot study [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 P5-14-09.
Abstract P5-15-04: Oncotype DX cost effectivity to a Brazilian public hospital
Authors: Cabello C , de Andrade RN , Cabello TF , Teixeira S , da Costa LS , Ramalho S 
Published: May 2019

Abstract
Introduction: The Oncotype DX was associated to 14% of adjuvant chemotherapy administration to Hormonal Receptor positive (HR+) and HER2 negative, T1N0 or T2N0 breast cancer patients at Tailor X trial recently published (RS&gt;25)
Objective: To describe the adjuvant chemotherapy administration to a Brazilian public hospital for HR+ HER2 negative, T1N0 or T2N0 breast cancer patients. And the estimate the cost effectivity of Oncotype DX in our low income scenary.
Materials and Methods:This retrospective cross-sectional study was conducted at the Oncology Division of the Women's Hospital - CAISM of the State University of Campinas (UNICAMP), Brazil. All patient data were found from the hospital records from 2007 to 2009. It was included T1N0 and T2N0 HR+/HER2 negative breast cancer patients. Patients submitted to neoadjuvant treatment were excluded.
We calculate the final cost of different types of chemotherapy used and the potential impact to oncotype DX introduction in this scenary.
Results: It was found 109 patients records. 66% (72/109) had received adjuvant chemotherapy. 35% (38/109) had AC (X6), 29% (32/109) had CMF (X6) and 2% (2/109) had AC-T (X4). The total cost for chemotherapy scheme were; AC (X6) US$ 346,9; CMF (X6), US$300,6; ACT (X4), US$395,9. The total cost of chemotherapy was US$ 23.596,83 to 72 patients. If we consider 14% (15/109) of adjuvant chemotherapy associate to a Oncotype DX use (Tailor X RS&gt;25), It would reduce adjuvant chemotherapy administration to 15 patients. The chemotherapy cost would be US$ 4588,27. In our scenary, It could save US$ 19.008,56. Nevertheless, the Oncotype Dx cost to Brasil is US$ 3.200,00 for each test. To 109 patients the total cost would be (109 X US$ 3.200,00) US$ 348.800,00. Therefore, the total cost for Oncotype DX program plus adjuvant chemotherapy for our patients would be US$ 348.800,00 + US$ 4.588,27= US$ 353.388,27. While in the real situation we had spent US$ 23.596,83. The total estimate cost would be 15 times more.
Conclusion: At the moment, because of the assay high cost and the low cost of the adjuvant chemotherapy to HR+, HER2 negative T1N0 and T2N0, It would be difficult to consider Oncotype DX cost-effective to Brazilian public heath system. Even considering many advantages to spare chemotherapy to this population.
Citation Format: Cabello C, de Andrade RN, Cabello TF, Teixeira S, da Costa LS, Ramalho S. Oncotype DX cost effectivity to a Brazilian public hospital [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 P5-15-04.