bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-13-14: Triple positive breast cancer ; a distictive subtype and consideration of systemic therapeutic approach
Authors: Kim JS , Kim YS , You SH 
Published: February 2018

Abstract
Introduction: Triple positive breast cancer is one of intrinsic subtype in breast cancer that is defined namely, ER/PR/Her2 positive tumors. It has multiple strategies for systemic therapy according to the characteristics of hormonal and anti-HER2 responsiveness. Each targeted therapy plays cross-talks between HER-2 and estrogen receptor signaling pathway resulting in endocrine resistance and anti Her2 resistance.
Methods: We compared the triple positive subtype to the other breast cancer intrinsic subtypes to distinguish the uniqueness in their position among other breast cancer subtypes using retrospective analysis of two different cohorts; Korea Breast Cancer Society (KBCS) Breast cancer registry data (N=31266, Jan. 2006 – Dec. 2010) and database from St. Mary`s hospital Breast cancer registry (N=2216, Apr. 2009 – Mar. 2016).
Results: Median follow up duration of 76 months in KBCS cohort (2006-2010) showed the overall survival graph of triple positive breast cancer located in the middle in between Luminal A intrinsic subtype and HER2 enriched subtype(P&lt;.001). Also HER2 directed trastuzumab therapy did not improve the overall survival in triple positive breast cancer patients (P=.899) in contrast to the improved overall survival using trastuzumab therapy in HER2 enriched subtype (P=.018). Like the preceding results, CMC breast cancer data showed the similar results in recurrence free survival (P&lt;.001). and no recurrence free survival improvement using trastuzumab therapy in triple positive breast cancer patient during the median follow up of 33 months (P=0.800).
Conclusion:
1) Anti-HER2 therapy seems less beneficial in Triple positive breast cancer subtype regardless of breast cancer stage.
2) Triple positive breast cancer may require different therapeutic approaches
3) Other targeted agents (mTOR inhibitor, CDK4/6 inhibitor, PIK3CA inhibitor) can be a substitute option for the Trastuzumab therapy in triple positive breast cancer.
Citation Format: Kim JS, Kim YS, You SH. Triple positive breast cancer ; a distictive subtype and consideration of systemic therapeutic approach [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-14.
Abstract P1-15-04: Outcome of small (≤1 cm), node-negative breast cancer
Authors: Muzaffar M , Namireddy P , Naqash R , Wong J , Vohra N 
Published: February 2018

Abstract
Background: Screening mammogram has resulted in increased diagnosis of very small breast cancers, especially less than 1 cm node negative. These small tumors have excellent prognosis with cancer-specific survival rates as high as 90% to 95%. This study evaluates outcome in different subtypes of very early breast cancer in a national population database.
Method: Patients with stage I breast cancer, tumor ≤ 1cm with negative nodes (T1aN0 (&lt;0.5cm), T1bN0 (≥ 0.5cm to ≤ 1cm) diagnosed between 2006 and 2011 were identified in the SEER database. We excluded patients with missing biomarker information. Treatment outcome and prognostic factors for disease-specific survival (DSS) and overall survival (OS) were evaluated.
Results: We identified 70,543 cases and included 54,796 patients with stage T1aN0M0 and T1bN0M0 in the final analysis. The mean age was 62.09 yrs. (CI 95% 62.2-61.99), 84% are white, 7% black and 7% others.89% had ER positive tumor, 11% ER negative and 3% had Her 2 positive tumors.71% of patients had T1b (≤ 1cm). The 5-year disease specific survival (DSS) and overall survival (OS) for patients with stage T1aN0, T1bN0 was 98.7% and 93.7%, respectively. Estrogen receptor (ER) positive tumors were associated with improved 5-yr DSS 99% vs. 96% in ER negative (p&lt;0.0001) and OS in ER positive 94% vs. 92%( p&lt;0.0001). Among white patients 5-yr DSS was 98.8% and OS was 93.7% while 5yr-DSS was 94%, OS 91.5% among black vs. 5-yr DSS 99% and OS 96.3% in others (Asian or Pacific Islanders, AI), (p&lt;0.0001). Tumor subtype was not associated with significant difference in outcome but T1a tumor was associated with OS 94.5% vs. 93.4% with T1b tumors (p&lt;0.0001) On cox model analysis factors which correlated with prolonged DSS and OS are race (p&lt;0.0001), older age (p&lt;0.0001), ER positivity (p&lt;0.0001) and tumor less than 5mm (p=0.0006).
Conclusions: Very early breast cancer is associated with excellent outcome but has some heterogeneity. Nonwhite/Non Black race was associated with better survival compared to white and black patients. ER positive tumors, and older age were also associated with better outcome. This data while reassuring also brings into question the overtreatment of this disease subset. One of the limitations of this dataset is lack of details of systemic therapy administered. Conventional prognostic factors are not sufficient to risk stratify very early breast cancer and molecular profiling may help identify patients who will need adjuvant treatment.
Citation Format: Muzaffar M, Namireddy P, Naqash R, Wong J, Vohra N. Outcome of small (≤1 cm), node-negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-04.
Abstract P2-02-01: Withdrawn
Authors: Turner NC , Garcia-Murillas I , Chopra N , Beaney M , Cutts RJ , Swift C , Kriplani D , Morden J , Hrebien S , Comino-Mendez I , Afentakis M , Bliss J , Skene A , Wheatley D , Russell S , Evans A , Dowsett M , Smith IE 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P2-02-17: Circulating tumor DNA analysis with ultra-high sensitivity sequencing in metastatic breast cancer
Authors: Garcia-Murillas I , Proszek P , Fribbens C , Yuan L , Bye H , Hubank M , Jiang J , Yuang S , Palma J , Johnston S , Ring A , Turner N 
Published: February 2018

Abstract
Introduction.
Circulating tumor DNA analysis has the potential to transform the clinical management of patients with breast cancer. We assessed the accuracy of ultra-high sensitivity ctDNA testing in patients with advanced breast cancer.
Methods.
From a prospective tissue collection study, we identified 25 patients with a contemporaneous metastatic tissue biopsy and plasma for ctDNA testing. Tumour DNA from the metastatic tissue biopsy was sequenced with a validated clinical hybrid capture panel, while plasma cell free DNA was sequenced with AVENIO ctDNA technology – a molecular barcoded duplex sequencing based on CAPPseq technology. Sample collection is on-going and results from the full concordance series will be presented at the conference.
Results.
Circulating tumour DNA was detectable in 87% (20/23) of patients, with at least one variant from tissue sequencing identified in plasma. There was overall high agreement between tissue and plasma sequencing. The sensitivity of plasma testing for variants identified in tumour, positive percent agreement, was 75% (24/32). Plasma testing revealed a diversity of sub-clonal mutations including polyclonal ESR1, polyclonal FGFR2 and FGFR3 mutations, rare KRAS mutations, and TSC1 and MSH2 inactivating mutations.
Conclusions.
Circulating tumour DNA testing with molecular barcoded duplex sequencing offers high sensitivity for tumour variant detection. The extent of sub-clonal resistance mutations identified emphasises the genetic diversity of advanced breast cancer.
Citation Format: Garcia-Murillas I, Proszek P, Fribbens C, Yuan L, Bye H, Hubank M, Jiang J, Yuang S, Palma J, Johnston S, Ring A, Turner N. Circulating tumor DNA analysis with ultra-high sensitivity sequencing in metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-02-17.
Abstract P2-03-09: An institutional look back: Maximizing the utility of MammaPrint® in invasive breast cancer diagnostics without breaking the bank
Authors: Cross AW , McEvoy JR 
Published: February 2018

Abstract
Background: Subtyping of invasive breast cancer utilizing immunohistochemical stains for estrogen receptor, progesterone receptor, and HER2, with or without the proliferation marker Ki-67, is the current standard of care employed by pathologists. The development of the BluePrint® molecular subtyping assay by Agendia, a microarray-based gene expression test used in conjunction with MammaPrint, to molecularly subtype and assess recurrence risk in early-stage breast cancer, has breast surgeons and oncologists challenging the status quo.
Study Objectives: With increasing emphasis placed of proper use of declining resources, the current study aimed to determine parameters in which such testing has the greatest added value.
Materials and Methods: All invasive breast cancer biopsies and resection specimens with formalin fixed paraffin embedded tissue sent for testing at Agendia Genomics Laboratory from April 2015 to May 2017 were reviewed in an institutional look back. 87 cases were reviewed and conventional immunohistochemical cancer profiling, tumor size, and grade were compared with MammaPrint prognostic reports.
Results and Discussion: Of the 87 cases compared, 67 (77%) showed concordance between immunohistochemical and molecular subtyping. Of the 20 discordant cases, 13 (65%) were subtyped as low risk luminal A by Mammaprint/BluePrint despite demonstrating high risk clinicopathologic features including larger size (average 2 cm vs overall average 1.4 cm), higher grade (1 low grade, 11 intermediate grade, and 1 high grade vs totals of 36 low grade, 42 intermediate grade, and 20 high grade), and increased proliferation indices. 3 (15%) of discordant cases revealed HER2 amplification by fluorescence in situ hybridization. Near complete agreement was found among basal subtype and Luminal A tumors with Ki-67 less than 12%, indicating the lack of added value among these cases.
Conclusion: Study results validate the limited role of MammaPrint/BluePrint in cases of invasive breast cancer. Specifically, the greatest value of MammaPrint/BluePrint was recognized in luminal subtypes with intermediate grade and proliferation indices ranging from 12 – 29%.
Citation Format: Cross AW, McEvoy JR. An institutional look back: Maximizing the utility of MammaPrint® in invasive breast cancer diagnostics without breaking the bank [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-09.
Abstract P2-05-03: Novel driver genetic alterations in MYB-NFIB-negative breast adenoid cystic carcinomas
Authors: Kim J , Geyer FC , Martelotto LG , Ng CKY , Lim RS , Selenica P , Li A , Pareja F , Fusco N , Edelweiss M , Mariani O , Badve S , Vincent-Salomon A , Norton L , Reis-Filho JS , Weigelt B 
Published: February 2018

Abstract
Introduction: Breast adenoid cystic carcinoma (AdCC) is a rare type of triple-negative breast cancer associated with an indolent clinical behavior. AdCCs provide a clear example of genotypic-phenotypic correlation with the majority harboring the MYB-NFIB fusion gene. In this study, we sought to identify alternative driver genetic alterations in breast AdCCs lacking the MYB-NFIB fusion gene.
Methods: Nucleic acids obtained from four breast AdCCs lacking the MYB-NFIB fusion gene as defined by reverse transcription (RT)-PCR and/or fluorescence in situ hybridization (FISH) were subjected to RNA-sequencing (n=3), whole-genome (n=2) and/or targeted (n=1) massively parallel sequencing. Sequencing data were analyzed using state-of-the-art bioinformatics algorithms, and potential alternative driver genetic alterations were validated using orthogonal sequencing and molecular pathology methods.
Results: RNA-sequencing revealed the presence of MYBL1-ACTN1 or MYBL1-NFIB fusion genes in two breast AdCCs, which were validated by whole-genome sequencing and/or MYBL1 FISH analysis. Both MYBL1 fusion gene-positive cases were found to overexpress MYBL1 as defined by quantitative RT-PCR analysis. In the third MYB-NFIB-negative breast AdCC studied, a high-level MYB gene amplification coupled with overexpression of MYB at the mRNA and protein levels was identified. In the fourth breast AdCC, which expressed high levels of MYB, whole-genome and RNA-sequencing revealed no definite alternative driver alteration, however, a MYBL2 intronic mutation was found in this case, which was associated with high levels of MYBL2 mRNA expression. In this case, single sample gene set enrichment analysis revealed activation of pathways similar to those activated in AdCCs harboring the MYB-NFIB or MYBL1 fusions genes.
Conclusion: We demonstrate that in breast AdCCs lacking the MYB-NFIB fusion gene MYBL1 rearrangements and MYB amplification are likely alternative driver genetic events. Given that activation of MYB/MYBL1 and their downstream targets can be driven by the MYB-NFIB fusion gene, MYBL1 rearrangements, MYB amplification or other yet to be validated mechanisms (e.g. MYBL2 non-coding mutations), our findings further suggest that breast AdCCs constitute a convergent phenotype.
Citation Format: Kim J, Geyer FC, Martelotto LG, Ng CKY, Lim RS, Selenica P, Li A, Pareja F, Fusco N, Edelweiss M, Mariani O, Badve S, Vincent-Salomon A, Norton L, Reis-Filho JS, Weigelt B. Novel driver genetic alterations in MYB-NFIB-negative breast adenoid cystic carcinomas [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-05-03.
Abstract P2-05-15: Oncotype DX Breast Recurrence Score®: Real-life utilization among node positive patients in Ontario
Authors: Richardson R , Macchiusi A , Bhasin A , Takizawa C 
Published: February 2018

Abstract
Aims: The 21-gene Oncotype DX (ODX) Recurrence Score (RS) has been extensively validated to predict the risk of distant recurrence and the magnitude of response to hormone and chemotherapy in patients with ER+ N0 and N+ (up to 3 positive nodes) HER2- early stage breast cancer. Outcomes data from multiple large studies further confirm the assays clinical validity and utility. The test is currently reimbursed in Ontario for N0 but not for N1 patients. In 2016, a market access program has been initiated to address lack of data in current clinical practice in Ontario among N1 patients. It collects data assessing the real-life use of the test in Ontario and its impact on treatment decision. This analysis presents the interim analysis until end of May 2017.
Methods : The program allows for prospective data collection in key breast cancer centers in Ontario. Through an online dedicated platform patient data are collected including classical pathological and clinical parameters (e.g. histology, tumor grade and size, ER, PR, and HER2 status), patients age, ODX Recurrence Score results and recommended treatment both before and after the test results have been reported.
Results: A total of 7 qualified breast cancer centers or network of centers participated in the program and collected 90 cases so far. Study results demonstrated that ODX is used among a wide variety of patients profiles: 28% G1, 58% G2 and 14% of G3, 18% pre-, 12% peri- & 69% are post-menopausal, 20% are aged 40-49, 24% are 50-59, 29% are 60-69 and 26% are 70 and older, 3% tumor are &lt;1cm, 38% are 1-&lt;2cm, 52% are 2-&lt;5cm and 7% tumor size are &gt;5cm.
RS distribution is the following: &lt;18 (67%), 18-30 (30%) and &gt;30 (3%).
In addition, pre-ODX 90% of patients had a treatment recommendation for chemo-hormonotherapy (CT-HT). Post-testing, the number of patients recommended CT-HT decreased to 36%, highlighting that the test reduces unnecessary use of CT. In fact, the ODX led to an overall 54% net reduction in chemotherapy.
Conclusions: This real-life survey confirms that ODX provides critical information beyond clinical and pathological criteria. The assay changes treatment decisions among N+ patients in Ontario, sparing CT which could result in potential savings to the healthcare system.
Citation Format: Richardson R, Macchiusi A, Bhasin A, Takizawa C. Oncotype DX Breast Recurrence Score®: Real-life utilization among node positive patients in Ontario [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-05-15.
Abstract P2-07-03: Systematic characterization of kinase inhibitors reveals heterogeneity in responses by class and cell line
Authors: Mills CE , Subramanian K , Hafner M , Chung M , Boswell SA , Everley RA , Juric D , Sorger PK 
Published: February 2018

Abstract
Several publications have addressed concerns surrounding drug response screens by pointing out sources of variability and by presenting recommendations for better experimental methods and more robust analytical approaches. In the presented profiling effort, we integrated the latest advances in drug response measurement and focused on data diversity and quality rather than on breadth. We selected 32 breast cancer cell lines with a strong bias towards triple negative lines as well as 4 cell lines established from relevant patient-derived xenografts. We evaluated a panel of clinically relevant kinase inhibitors using a microscopy-based dose response assay to measure drug potency, and to quantify drug efficacy in terms of growth inhibition (GR metrics) and cell death. The use of the GR metrics to quantify drug sensitivity enabled us to identify and study differences between cytostatic and cytotoxic responses. This systematic dose response dataset is complemented by measurements of baseline transcript expression levels by mRNAseq, quantification of absolute abundance of ˜12,000 proteins, and relative phosphoprotein levels by shotgun mass spectrometry across all cell lines. Additionally, the baseline activity of transcription factors and kinases were inferred from the mRNA (using VIPER) and phosphoprotein (using kinase enrichment analysis) data, respectively. The complementarity of these multi-omics data has allowed us to address questions about the landscape of breast cancer cell lines such as: Where do the patient-derived lines lay relative to the conventional cell lines? How consistent are the landscapes defined by each dataset? How does integration across datasets provide mechanistic insight into signaling pathways that are active in each cancer subtypes? The measured and inferred baseline data were used to build predictors of the observed drug responses with the goal of identifying the biological processes responsible for the differences in sensitivity across drugs and cell lines. Overall the dataset that has been collected is a valuable resource for understanding drug response in triple negative breast cancer, and the molecular mechanisms that influence it.
Citation Format: Mills CE, Subramanian K, Hafner M, Chung M, Boswell SA, Everley RA, Juric D, Sorger PK. Systematic characterization of kinase inhibitors reveals heterogeneity in responses by class and cell line [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-07-03.
Abstract P2-07-06: Multi-omics characterization of claudin-low breast tumors
Authors: Pommier RM , Morel A-P , Tissier A , Thomas E , Kielbassa J , Tonon L , Sohier E , Viari A , Saintigny P , Puisieux A 
Published: February 2018

Abstract
Breast tumors display highly heterogeneous characteristics both at transcriptional level and in term of genomic landscape. We recently reported that the differentiation status of the cell-of-origin influences the genetic route toward tumorigenesis1. Indeed, mammary stem cells exhibit the intrinsic property to tolerate the oxidative stress inherent to the oncogenic transformation through the expression of a preemptive program driven by ZEB1, an epithelial-to-mesenchymal transition (EMT)-related transcription factor, and MSRB3, a methionine sulfoxide reductase. Thereby, ZEB1-expressing tumors exhibit low level of DNA damage associated with few genomic alterations and low level of TP53 mutations. Importantly, these tumors share several transcriptional characteristics and features with normal stem cells, and with Claudin-Low (CL) molecular subtype of breast cancers. In the present work, we attempt to decipher molecular traits of CL breast tumors through multi-omics analyses of publicly available databases. This global approach allows us to highlight various CL breast tumors features as clinical attributes, gene expression, copy number alterations (CNA), somatic mutations or drug responses by differential analyses of breast tumors and cancer cell lines. Preliminary results indicate that, independently of tumor purity, CL breast tumors are mostly diploids, present a paucity of genomic rearrangements and a lower mutation rate compared to other breast tumors. They mainly, but not exclusively, show basal features and belong to the integrative cluster 4 (CNA-devoid) described by Christina Curtis and colleagues2. Concerning gene expression, CL breast tumors exhibit a frequent activation of RAS signaling pathway, an observation consistent with their sensitivity to MAPK inhibitors. Other analyses are currently ongoing and aim to better understand the biology of CL breast tumors in order to improve both the diagnosis and the therapeutic strategy used.
1. Morel A-P et al. A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability. Nature Medicine. 2017 Apr 10.
2. Curtis C et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012 Apr 18.
Citation Format: Pommier RM, Morel A-P, Tissier A, Thomas E, Kielbassa J, Tonon L, Sohier E, Viari A, Saintigny P, Puisieux A. Multi-omics characterization of claudin-low breast tumors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-07-06.