bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-03-39: Sentinel lymph node biopsy after surgery with removal of the primary tumor
Authors: Zhiltsova E , Krivorotko P , Dashayan G , Emelyanov A , Tabagua T , Bessonov A , Ivanova O , Kanaev S , Novikov S , Krzivickiyi P , Komayachov A , Nikolaev K , Gigolaeva L , Zernov K , Semiglazov V 
Published: May 2019

Abstract
Nowadays, sentinel lymph node biopsy (SLNB) is one of the basic methods for
diagnosing the lesion of regional lymph nodes (LN) and it is recommended by
experts as a standard method in determining the prevalence of the disease in breast
cancer patients (BC).
The aim of the study was the possibility of sentinel lymph node biopsy after
surgery with removal of the primary tumor.
Materials and methods
The study was conducted in the N.N. Petrov's National Medical Center of
Oncology from 2013 to 2018. SLNB was performed in patients who had a primary
tumorectomy in another medical institution. The study included patients with the
stage cN0. Radionuclide imaging of the sentinel lymph nodes (SLN) was
performed in 37 patients with breast cancer. The injection of radiopharmaceuticals
in postoperative scar was performed before the biopsy. Median of the period
between the operations was 21 days (14 to 30 days).
Results
After injection, the image of SLN was obtained in 91.9% (34 of 37) of patients.
During the operation, 1-5 sentinel lymph nodes were visualized. The lesion of the
sentinel lymph nodes (N+) was detected in 21.6% (8) patients, N0 in 78.4% (29)
patients, respectively.
There is no data for locoregional relapse for the period of observation from 2014 to
nowadays.
Conclusions
The obtained results are comparable with the results of sentinel lymph node biopsy
in primary patients with breast cancer stage cN0. This indicates the possibility of
biopsy after surgery with removal of the primary tumor.
Citation Format: Zhiltsova E, Krivorotko P, Dashayan G, Emelyanov A, Tabagua T, Bessonov A, Ivanova O, Kanaev S, Novikov S, Krzivickiyi P, Komayachov A, Nikolaev K, Gigolaeva L, Zernov K, Semiglazov V. Sentinel lymph node biopsy after surgery with removal of the primary tumor [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 P3-03-39.
Abstract P3-06-03: Copy number analysis identifies ESR1 and MDM4 as drivers of progression in invasive lobular breast carcinoma
Authors: Atkinson JM , Cao L , Basudan A , Sikora MJ , Bahreini A , Tasdemir N , Jankowitz RC , McAuliffe PF , Dabbs D , Haupt S , Haupt Y , Peter Lucas PC , Lee AV , Oesterreich S 
Published: May 2019

Abstract
Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma (IDC). While specific clinical and pathological features differ between ILC and IDC, both histologies are treated the same, due to a lack of knowledge of targetable pathways underlying the observed differences. To identify potential genetic drivers of ILC progression, we set out to identify genes with copy number (CN) alterations, comparing tumors with good outcome to those with poor outcome.
Method: We designed probes for a total of 67 genes known to be frequently altered in breast cancer and used sensitive nanoString technology to comprehensively investigate CN alterations of these genes in 70 well-curated primary ILCs. ILC cell lines MDA-MB-134-VI, SUM44PE, and BCK4 were used for functional studies including proliferation, apoptosis, colony formation, and analysis of gene expression.
Results: Our studies reveal that ESR1 is frequently amplified in primary ILC (14% gains and 10% amplification), and that tumors with amplified ESR1 are more likely to recur compared to those with normal CN. Our analysis also identified a subset of ILCs with HER2 amplification (19%) despite a negative clinical IHC score, and these tumors expressed high HER2 mRNA, protein, and demonstrated enrichment of a molecular HER2 signature. The other most frequently amplified genes included CCND1 (33%), MDM4 (17%), and MYC (17%), and most frequently lost genes were NCOR2 (7%), FGFR4 (6%) and TP53 (6%). MDM4, a negative regulator of p53, has previously been reported to play a role in breast cancer, though little is known about its role in ILC. We demonstrate that decreasing MDM4 levels in p53 wild type ILC cell lines results in increased apoptosis, decreased proliferation associated with cell cycle arrest, and activation of p53 target genes. Intriguingly, a similar induction of G0/G1 cell cycle arrest and increase in apoptosis was observed in p53 mutant ILC cells after MDM4 downregulation, suggesting a p53-independent function of MDM4.
Conclusion: Sensitive detection of CN changes identified amplifications of ESR1 and MDM4 as potential drivers of ILC. Functional studies demonstrate that MDM4 has both p53 dependent and independent functions that warrant further study.
Citation Format: Atkinson JM, Cao L, Basudan A, Sikora MJ, Bahreini A, Tasdemir N, Jankowitz RC, McAuliffe PF, Dabbs D, Haupt S, Haupt Y, Peter Lucas PC, Lee AV, Oesterreich S. Copy number analysis identifies ESR1 and MDM4 as drivers of progression in invasive lobular breast carcinoma [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 P3-06-03.
Abstract P3-06-05: Whole genome sequence analysis of 77 breast cancer patients reveal increased somatic transposable element insertions responsible for early onset of cancer
Authors: Paul R , Solzak JP , Radovich M 
Published: May 2019

Abstract
More than 50% of the human genome consists of transposable elements (TE). However only certain classes of retrotransposons (ALU, SVA, ERV and L1) are believed to be active. They transpose using an RNA intermediate causing target-site duplications along with a poly-A tail. They can also insert into intronic regions and disrupt normal transcription of protein-coding genes. However, most TEs are repressed using various epigenetic mechanisms such as DNA methylation, histone modifications and RNA silencing. The piRNA pathway also plays an important role in retrotransposon silencing by establishing a repressive chromatin state. In this study, somatic and germline TE insertions in 77 TCGA breast cancer cases were characterized. These studies have revealed that somatic TEs can insert into intronic regions of tumor suppressor genes such as LRP1B, RAD51B and WNK2. Characterization of germline TE insertions, reveal insertions in intronic regions of predisposition genes such as CDH1 and BRCA2. Analysis of germline SNPs in high somatic TE patients reveals the presence of deleterious variants in genes such as NRDE2, RAD51C and DDX3X which are known to regulate TEs using RNA silencing via the piRNA pathway and other DNA-damage response mechanisms. Patients having high somatic TE insertions were found to have lower age of diagnosis suggesting a role in the early onset of cancer (median age of patients with high TE=43.37yrs; low TE=59.77yrs, Wilcoxan p=0.023). Further comparison of somatic TE insertion burden against somatic point-mutation burden revealed an inverse correlation suggesting analysis of TE insertions is indispensable to get the complete mutation profile of breast cancer genomes.
Citation Format: Paul R, Solzak JP, Radovich M. Whole genome sequence analysis of 77 breast cancer patients reveal increased somatic transposable element insertions responsible for early onset of 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 P3-06-05.
Abstract P3-06-13: Whole exome sequencing of HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary durable complete responses (ExdCR) to trastuzumab (T)
Authors: Walsh N , Gullo G , Quinn C , Furney SJ , Crown J 
Published: May 2019

Abstract
Background: Trastuzumab (T) has shown clinical efficacy in early-stage and MBC. However, within 1-year 40-50% develop resistance to T. The exact mechanism of the development of T resistance is not completely understood. Anecdotal observations suggest that a small fraction of patients with HER2+ MBC may be "extraordinary durable complete responders (ExdCR)". Indeed, we previously reported that 9% of MBC achieve dCR following T and chemotherapy. Understanding the genomic mechanisms underlying exceptional dCR to T may improve patient selection and treatment rationale to identify HER2+ MBC pts who are more likely to achieve dCR following T treatment.
Methods: Genomic DNA was extracted from paraffin embedded formalin fixed (FFPE) tissue. Whole exome sequencing (WES) on primary tumours from 9 MBC ExdCR &gt; 60 mo (5 matched T:N) and 6 non-responders (NR) or PR &lt; 6 mo (3 matched T:N). Tumours were analysed for single nucleotide variants (SNVs) point mutations, insertions/deletions (indels), copy number alterations (CNA), and tumour mutational burden. Detailed clinicopathologic data was collected for each patient and linked to the genomic information.
Results: WES of matched tumour:normal samples revealed differences in SNVs and indels between the ExdCR pts compared to NR. Mutations in TP53 were found in 2/5 ExdCR pts and in 0/3 NR. Initial analysis of CNA revealed that HER2 is significantly more amplified in ExdCR pts compared to NR, and this was also shown by IHC and FISH.
Conclusions: We present a genomic landscape of extraordinary durable complete responders compared to non-responders using WES. High variability exists in mutation profile of ExdCR pts with few overlapping genes. Further analysis into clinically relevant genomic and molecular alterations will be performed to potential aid in patient selection and choice of therapy, and novel drug targets.
Citation Format: Walsh N, Gullo G, Quinn C, Furney SJ, Crown J. Whole exome sequencing of HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary durable complete responses (ExdCR) to trastuzumab (T) [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 P3-06-13.
Abstract P3-06-18: Comprehensive genomic profiling of carcinosarcomas of the breast
Authors: Gay LM , Elvin JA , Vergilio J-A , Killian JK , Ramkissoon S , Severson E , Daniel S , Hammerich A , Sokol E , Frampton G , Chung J , Trabucco S , Ali S , Reddy P , Schrock AB , Miller VA , Ross JS 
Published: May 2019

Abstract
Background:
Carcinosarcomas of the breast (BCSC) are exceptionally rare and the underlying genomic drivers are still being elucidated. Comprehensive genomic profiling (CGP) determines the tumor mutation burden (TMB) and identifies all four classes of genomic alterations (GA) that have potential to direct personalized treatment strategies.
Methods:
CGP by hybridization capture of exons from up to 315 cancer-related genes and select introns of 28 genes commonly rearranged in cancer was applied to ≥ 50ng of DNA extracted from 9 consecutive BCSC and sequenced to high, uniform median coverage (&gt;500X). Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined by principal components analysis of optimized loci.
Results:
The 9 BCSC patients had a median age of 57 yrs (range 49-78 yrs). CGP was performed on the primary BCSC in 4 cases and on metastasis biopsies in 5 cases (4 lung and 1 lymph node). The mean GA/tumor was 6.6 and clinically relevant GA (CRGA)/tumor was 1.3. The most frequent non-CRGA were in TP53 (89%), MYC (56%) and LYN (40%). The most frequent CRGA were in PIK3CA (33%), and NF1, BRCA1, PTEN, RICTOR, FGFR1, AKT2 and STK11 (all at 11%). The median TMB for all BCSC was 2.4 mut/Mb with 1 (11%) tumor with a TMB &gt; 20 mut/Mb and 8 BCSC (88%) with TMB &lt; 5 mut/Mb. Five of 5 BCSC (100%) that were available for MSI status testing were microsatellite stable.
Conclusions:
On CGP, BCSC feature a high frequency of GA, but only a modest frequency of CRGA and high TMB. However, when the CRGA and TMB positive cases are combined (77.8% overall in this series), the opportunity for personalized targeted and immunotherapies are significant. Thus, further investigation of precision therapies for BCSC in the clinical trial setting appear warranted.
Citation Format: Gay LM, Elvin JA, Vergilio J-A, Killian JK, Ramkissoon S, Severson E, Daniel S, Hammerich A, Sokol E, Frampton G, Chung J, Trabucco S, Ali S, Reddy P, Schrock AB, Miller VA, Ross JS. Comprehensive genomic profiling of carcinosarcomas of the breast [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 P3-06-18.
Abstract P3-06-19: MUC17 and PCNX1 as mediators of chemotherapy response in breast cancer
Authors: Al Amri W , Verghese E , Stead L , Hanby A , Sharma N , Hughes T 
Published: May 2019

Abstract
Breast cancer is a heterogeneous disease and accumulating evidence suggests that treatment failure may be driven by intra-tumour heterogeneity (ITH). Utilising the current protocol for neoadjuvant (pre-surgery) chemotherapy (NAC) provides the opportunity to study molecular genetic changes between pre- and post-therapy by assessing pre-therapy biopsies and post-therapy surgical resections.
Whole exome sequencing was performed on matched pre- and post-treatment cancer cells from 6 patients with oestrogen receptor positive breast cancers that showed partial responses to the chemotherapeutic epirubicin. Data analysis was performed to determine differences in genetic aberrations between pre- and post-NAC, and in particular to identify evidence of consistent selection by therapy of aberrations that therefore may define chemotherapy resistance or sensitivity.
There were extensive differences in the range of genetic aberrations between pre- and post-NAC. 48 genes were identified for further study based on evidence of mutations conferring a selective advantage or disadvantage during chemotherapeutic response. The relevance of these was screened using siRNA knock-down and assessment of response to chemotherapeutic drug using cell viability assays in vitro. Two genes were taken forward. Potential loss-of-function mutations in the MUC17 gene were selected against during therapy in patients, and in accordance with this MUC17 knock-down was associated with increased sensitivity in vitro. Potential loss-of-function mutations in the PCNX1 gene were selected for during therapy in patients, and in accordance with this PCNX1 knock-down was associated with resistance. Further work was done to investigate mechanisms by which these genes modify cellular chemotherapy response, by examining drug loading and ABC transporter expression levels. Data indicate that both genes impact on drug loading, potentially through modulating ABC transporter activities. Using available transcriptomic datasets, expression of neither gene correlated with breast cancer outcomes in mixed cohorts that received a wide-range of therapies, however, analysis of correlations between protein expression and outcomes specifically after chemotherapy are on-going. We conclude that MUC17 and PCNX1 are potential markers of response to chemotherapy in breast cancer, and therapeutic modulation of their activities could enhance chemotherapy responses.
Citation Format: Al Amri W, Verghese E, Stead L, Hanby A, Sharma N, Hughes T. MUC17 and PCNX1 as mediators of chemotherapy response in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-06-19.
Abstract P3-06-21: Withdrawn
Authors: Minhas S , Veldore V , Ramprasad V , Ganvir M , Aggarwal S 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Minhas S, Veldore V, Ramprasad V, Ganvir M, Aggarwal S. Withdrawn [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 P3-06-21.
Abstract P3-07-09: Tumour clonality in paired invasive breast carcinomas
Authors: Biermann J , Parris TZ , Nemes S , Danielsson A , Engqvist H , Werner Rönnerman E , Forssell-Aronsson E , Kovács A , Karlsson P , Helou K 
Published: May 2019

Abstract
Background: Multiple invasive breast tumours may represent either independent primary tumours or clonal recurrences of the first tumour, where the same progenitor cell gives rise to all of the detected tumours. Consequently, the driver events for the progenitor cell need to have been identical in early tumour development. Molecular classification of tumour clonality is not currently evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. Furthermore, there is no consensus about which type of biological data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.
Methods: Thirty-seven invasive breast tumour pairs were stratified by laterality (bilateral vs. ipsilateral) and the time interval between the diagnoses of the first and second tumours (synchronous vs. metachronous). Both tumours from the same patient were analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), distance measure, shared segment analysis etc., were used to classify the tumours from the same patient as clonally related recurrences or independent primary tumours.
Results: The SI applied on DNA copy numbers derived from aCGH (array comparative genomic hybridization) data was determined as the strongest indicator of clonal relatedness as it showed the highest concordance with all other methods. The distance measure was the most conservative method and the shared segment analysis most liberal. Concordant evidence for tumour clonality was found in 46% (17/37) of the patients. Notably, no significant association was found between the clinical characteristics and molecular tumour features.
Conclusions: A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. In cases of extremely similar or different tumour pairs, the results showed consistency regardless of the method used. The SI can be easily integrated into clinical routine using FFPE samples to obtain copy number data. However, clinical guidelines with exact thresholds need to be defined to standardize clonality testing in a routine diagnostic setting.
Citation Format: Biermann J, Parris TZ, Nemes S, Danielsson A, Engqvist H, Werner Rönnerman E, Forssell-Aronsson E, Kovács A, Karlsson P, Helou K. Tumour clonality in paired invasive breast carcinomas [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 P3-07-09.
Abstract P3-08-19: Proteomic tracking of breast cancer metastasis progression
Authors: Hajjaji N , Aboulouard S , Robin YM , Bertin D , Fournier I , Bonneterre J , Salzet M 
Published: May 2019

Abstract
Background
Metastases from breast cancers have not yet reached curability mainly because of the continuous evolution of cancer cells leading to treatment resistance and tumor progression. Despite the identification of the main genomic drivers of breast cancer resistance, and the development of specific targeted therapies, resistance has not been eradicated. A deeper understanding of tumor biology underlying treatment escape and tumor progression is necessary to find new targets. The aim of this study was to determine whether mass spectrometry based imaging and microproteomics are able to capture changes in protein expression and pathways occurring during metastasis progression.
Methods
Ten tumor samples from five progressing metastatic breast cancer patients treated at Oscar Lambret Cancer Center (France) were selected based on the availability of paired metastasis biopsy performed at two time points during the evolution of the disease. The proteomic profiles of paired tumor samples were analyzed using MALDI mass spectrometry imaging combined with microproteomics, a spatially resolved proteomic technology.
Results
Comparison of paired samples showed gain and loss of proteins associated with tumor progression. However, few were shared between patients. The pathways and biological processes mainly represented during tumor progression, and which were found in at least two patients, were those involved in the negative regulation of leukocyte mediated cytotoxicity, the metabolism of carboxilic acid, peptides and nucleosides, in response to stress, oxidation-reduction process, endocytosis, catabolic processes, actin regulation, and extracellular matrix organization. During metastasis evolution, few shared proteins were identified in at least 3 patients such as SRPX2, CILP1, collagen alpha-2(V) chain, Ras-related C3 botulinum toxin substrate 1, filamin-C, PDZ and LIM domain protein 2 and chloride intracellular channel protein 4. The main proteins lost during progression and found in at least 2 patients were cell surface glycoprotein MUC18, collagen alpha-2(IV) chain, polyadenylate-binding protein 2, and latent-transforming growth factor beta-binding protein 4 (LTAGP4). Results from an expanded cohort will be presented at the meeting.
Conclusion
MALDI mass spectrometry proteomics identified private and shared changes in proteins and biological processes associated with breast cancer metastasis progression.
Citation Format: Hajjaji N, Aboulouard S, Robin YM, Bertin D, Fournier I, Bonneterre J, Salzet M. Proteomic tracking of breast cancer metastasis progression [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 P3-08-19.
Abstract P3-08-21: Not presented
Authors: Stanek L , Tesarova P , Vocka M , Petruzelka L , Musil Z 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Stanek L, Tesarova P, Vocka M, Petruzelka L, Musil Z. 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 P3-08-21.