bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-12-06: Results of next-generation sequencing panels in a large community-based hereditary cancer risk program
Authors: Blum J L , Garby C A , Simmons A E , Walker S A , Panos L E 
Published: May 2015

Abstract
Background: Next-generation sequencing (NGS) allows for broader germline genetic testing for hereditary cancers. Since the Supreme Court decision of AMP v. Myriad on June 13, 2013, hereditary cancer multi-gene panels can now include BRCA1 and BRCA2, making these panels an option for first-tier testing. However, questions have been raised about the clinical utility and implications of extended panels for medical management given the inclusion of unknown to moderate penetrant genes.
Methods: We reviewed all patients who underwent multi-gene panel testing from July 1, 2013 through May 23, 2014. The indications for testing included personal and/or family history of breast or ovarian cancer. The panels were ordered in a single genetic counseling clinic within a large community-based cancer center.
Results: A total of 136 patients underwent panel testing via a single commercial laboratory. We identified 12 (8.8%) patients who were positive for a pathogenic or likely pathogenic mutation in a cancer susceptibility gene; 4 had prior negative BRCA1 and BRCA2 sequencing and deletion/duplication testing. These positive results included 4 BRCA2 mutations, 2 TP53 mutations, 1 CDH1 mutation, 2 ATM mutations, and 1 patient each with a CHEK2, NBN, or PALB2 mutation. Of the patients found to have a positive test result, 100% met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer (HBOC) genetic testing. The CDH1 mutation carrier did not meet NCCN guidelines for hereditary diffuse gastric cancer testing and only one of the TP53 mutation carriers met NCCN guidelines for Li-Fraumeni syndrome. Within our cohort (136), 21 (15.4%) patients had a total of 25 variants of uncertain significance (VUS) and 103 (75.7%) patients had negative test results.
Conclusion: Testing through NGS panels identified 7/12 (58%) patients with a mutation which led to changes in current medical management and 3/7 (43%) had a mutation in a gene other than BRCA1 or BRCA2. Our findings suggest that there is clinical utility of NGS panels for use in this patient population despite the inclusion of unknown to moderate penetrant genes and a higher rate of VUS than single gene testing.
Citation Format: J L Blum, C A Garby, A E Simmons, S A Walker, L E Panos. Results of next-generation sequencing panels in a large community-based hereditary cancer risk program [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-06.
Abstract P4-12-12: Next generation sequencing-based analysis of BRCA1 and BRCA2 genes: Applicability for fast diagnostics of large samples
Authors: Kong Sun-Young , Cho Eunhae , Lee Junnam , Lim Myong Cheol , Jang Jahyun , Park Boyoung , Yoon Kyong-Ah , Kim Young-Ho , Lee Eun Sook 
Published: May 2015

Abstract
Purpose
BRCA1&2 gene mutation test for hereditary breast ovarian syndrome (HBOC) has been conducted mostly by Sanger sequencing. Currently, the next generation sequencing (NGS) is rapidly incorporated to the fields of cancer research and clinical diagnostics. Here we evaluated NGS-based results of BRCA gene analysis and compared with the results of Sanger sequencing for future diagnostic applications.
Methods
The patients (n=100) who have genetic counseling and decided to perform BRCA test were included. All coding regions of BRCA1 and BRCA2 analyzed by both of Sanger sequencing and NGS using Access Array BRCA1, BRCA2 and TP53 kit (Fluidigm, USA). Access array kit was designed to multiplex 48 samples simultaneously for 184 amplicons and the average sequencing depth per base was 6,500X using MiSeq sequencer (Illumina, USA). We developed analysis pipelines to avoid false negative results and detect all pathogenic mutations. The reads were aligned to a reference genome (NCBI human genome assembly build 37) using the BWA-MEM, then all candidate variants called with minimum filtering parameter.
Results
Total of 765 variants were detected by NGS and among them 616 variants (frameshift:22, nonsense:8, splicing:3, missense:290, and synonymous variants:293) were identical with the results from Sanger sequencing. When we evaluated the results of Sanger sequencing as standard methods, the mean allele frequency showed difference as 41.7% and 12.0% for true positive heterozygous variants (616) and false positive variants (149), respectively.
Conclusions
There was no false negative of pathogenic mutations from NGS. The BRCA mutation detection using NGS represented potential applicability in clinical diagnosis.
Citation Format: Sun-Young Kong, Eunhae Cho, Junnam Lee, Myong Cheol Lim, Jahyun Jang, Boyoung Park, Kyong-Ah Yoon, Young-Ho Kim, Eun Sook Lee. Next generation sequencing-based analysis of BRCA1 and BRCA2 genes: Applicability for fast diagnostics of large samples [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-12.
Abstract P5-01-03: Opto-acoustic nomograms for improving breast cancer diagnosis
Authors: Lavin Philip , Stavros Thomas 
Published: May 2015

Abstract
Background/Objective:
Diagnostic specificity remains disappointingly low for ultrasound-based methodologies optimized to achieve near 100% sensitivity. Opto-acoustic (OA) imaging is a fusion of real time co-registered, interleaved laser optic and ultrasound imaging that shows fused functional findings (relative de-oxygenation of hemoglobin) and morphologic information (tumor angiogenesis) within and around breast masses using a hand-held duplex OA probe. We assess the improvement in sensitivities and specificities of nomograms (N) based on regression models to classify (CL) benign (B) vs. malignant (M) and to project probability of malignancy (POM) based on five feature-based metrics scored by 21 independent readers (IRs) and an expert reader. We examine OA feature separation and nomogram performance.
Methods:
Masses from a series of 100 subjects with 80 biopsies (42 B, 38 M) were blindly evaluated prior to both core biopsy and excision. The OA algorithm was locked. Three internal OA findings (density of vascularity [V], relative blood oxygen saturation [O], and hemoglobin [H]) and two external OA findings (boundary zone [Z] and peri-tumoral radiating vessels [R]) were assigned 0-5/6 ordinal scores. Feature distributions were compared using a two-sided Kruskal-Wallis test.
Results:
There were consistently significant differences between the feature distributions for benign vs. malignant: density of vascularity (14/21 IRs), relative blood oxygen saturation (11/21 IRs), hemoglobin (16/21 IRs), boundary zone (all IRs), and peri-tumoral radiating vessels (all IRs) always with lower scores for benign vs. malignant. The mean IR sensitivities were near 100% for all IRs. The mean specificities from the nomograms were 49% (POM), 43% (CL), and 48% (averaged).
Conclusions:
The study results indicate that OA findings can be independently and quickly mastered by practicing IRs to consistently differentiate masses. Nomograms offer further confidence to enhance decision making to differentiate. If confirmed in a larger series, OA findings might be useful in differentiation and thus sparing biopsies in addition to more customized surgeries.
Citation Format: Philip Lavin, Thomas Stavros. Opto-acoustic nomograms for improving breast cancer diagnosis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-03.
Abstract P5-01-10: In vitro and in vivo imaging of Her2 with cyclic peptides derived from directed evolution
Authors: Kelderhouse Lindsay E , Hardy Amanda , Pan Yong , Rhea Patrea , Ornelas Argentina , Gammon Seth , Yang Peiying , Fiacco Stephen , Millward Steven W 
Published: May 2015

Abstract
The implementation of personalized medicine for Her2-positive breast cancer treatment (Trastuzumab and Pertuzumab) has made a dramatic effect on overall patient outcome. Unfortunately, there are currently no FDA-approved imaging agents to monitor Her2-positive breast cancer leaving physicians to rely on invasive biopsies and anatomical imaging to monitor treatment with Her2-targeted therapeutics. There is also increasing evidence that women initially diagnosed with Her2-negative breast can present with Her2-positive disease upon recurrence. Noninvasive, whole-body visualization of Her2 would identify Her2-recurrent disease and serve as a powerful tool to monitor the effectiveness of new and emerging Her2-targeted therapeutics (e.g. TDM-1). While many Her2-antibody based imaging agents have been used in preclinical applications, their long circulating half-lives, high liver uptake, and poor synthetic accessibility pose a challenges for clinical translation. Here we describe the use of highly stable cyclic peptides derived from biological display as imaging agents for Her2-positive breast cancer. These peptides have antibody-like high affinity (&lt;10 nM) for Her2-positive tumors and their size (&lt;2 kDa) allows for higher rates of clearance, lower background signal, and consequently higher image sensitivity. Anti-Her2 peptides were pre-optimized for affinity, protease resistance and bio-stability prior to labeling with the Cy7.5 near-infrared dye. Her2-specificity was determined by in vitro assays with Her2-postive (BT474 and SKOV3), HER2-normal (MCF7) and Her2-negative (MDA-MB-231) cell lines. Sequences that showed superior affinity and selectivity were used to acquire fluorescent images of ectopic and orthotopic murine models of Her2-positive breast cancer. Our preliminary imaging data suggests that this scaffold has excellent translational potential for targeted molecular imaging of Her2-postive breast cancer.
Citation Format: Lindsay E Kelderhouse, Amanda Hardy, Yong Pan, Patrea Rhea, Argentina Ornelas, Seth Gammon, Peiying Yang, Stephen Fiacco, Steven W Millward. In vitro and in vivo imaging of Her2 with cyclic peptides derived from directed evolution [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-10.
Abstract P5-01-13: The spectroscopic feature of breast cancer
Authors: Ogura Hiroyuki , Yoshizawa Nobuko , Yoshimoto Kenji , Nasu Hatsuko , Taki Yumiko , Hosokawa Youko , Matsunuma Ryouichi , Ide Yoshimi , Yamaki Etsuko , Suzuki Toshihiko , Oda Motoki , Ueda Yukio , Yamashita Yutaka , Sakahara Harumi 
Published: May 2015

Abstract
Objectives: To examine optical properties of breast cancer by time-resolved spectroscopy.
Materials and Methods: We irradiated a pulsed laser of 760, 800, and 830 nm wave-length lights at multiple sites of both breasts including the site just above the cancer and detected the light transmitted through the breast with TRS-20SH (Hamamatsu Photonics K.K.). Absorption coefficient (μa), reduced scattering coefficient (μs’), total hemoglobin (tHb), and oxygen saturation (SO2) of the breast were calculated by photon diffusion equation. The clinical trial started in January 2007. A total of one hundred fifty-two breast cancer patients participated in the trial and written informed consent were obtained from all of the patients.
Results: The absorption coefficient (μa) in 760, 800 and 830 nm wave-length of breast cancer tissue was significantly high compared with contra-lateral normal breast (760nm:cancer;0.078 normal;0.063 p&lt;0.001. 800nm cancer:0.071, normal;0.050, p&lt;0.001. 830nm: cancer;0.084, normal;0.063, p&lt;0.001).
The absorption coefficient and reduced scattering coefficient between breast cancer tissue and contra-lateral normal breast μa (/cm)μs'(/cm) cancernormal breastcancernormal breast760nm0.0780.0639.589.71800nm0.0710.059.239.4830nm0.0840.0639.079.22
There was no difference in reduced scattering coefficient (μs’) between breast cancer tissue and contra-lateral normal breast(760nm: cancer;9.58, normal;9.71, 800nm: cancer:9.23, normal;9.40. 830nm; cancer;9.07, normal;9.22). The tHb of breast cancer tissue was significantly high, compared with normal breast (cancer:32.3±14.6, normal breast;22.0±8.6, p=0.001). There was no difference in oxygen saturation (SO2) between breast cancer tissue and contra-lateral normal breast (cancer:73.2±4.3, normal breast;73.6±5.9, p=0.31).
The tHb and SO2 between breast cancer tissue and contra-lateral normal breast cancernormal breastp-valuetHb(μM)32.3±14.622.0±8.6p&lt;0.001SO2(%)73.2±4.373.6±5.9p=0.32
Conclusion: Absorption coefficient (μa) and tHb increased in breast cancer, whereas reduced scattering coefficient (μs’) and oxygen saturation did not.
Citation Format: Hiroyuki Ogura, Nobuko Yoshizawa, Kenji Yoshimoto, Hatsuko Nasu, Yumiko Taki, Youko Hosokawa, Ryouichi Matsunuma, Yoshimi Ide, Etsuko Yamaki, Toshihiko Suzuki, Motoki Oda, Yukio Ueda, Yutaka Yamashita, Harumi Sakahara. The spectroscopic feature of breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-13.
Abstract P5-02-09: Ki67-labelling index of luminal breast cancers: Agreement of core biopsy and surgical specimen results
Authors: Focke Cornelia M , Decker Thomas 
Published: May 2015

Abstract
Objective: To highlight the agreement between Ki67-Labelling indices (LIs) of core biopsies (CB) and related surgical specimens (SSP) in luminal breast cancers (BCs) adopting the recommendations of the St Gallen Consensus Conference 2013 and the International Ki67 In Breast Cancer Working Group.
Methods: We investigated CBs and the related SSPs of 220 luminal Her2 negative BCs. To assess the Ki67-LI a total of 510 tumour cells including hot spot, cold spot and an area of intermediate proliferation was counted by one observer. Every positive nucleus was counted, independent of the staining intensity. A Ki67-LI cut-off &lt;20% as recommended by the St Gallen Consensus was used to define luminal A BCs. Agreement between CB and SSP, rates of under- and overestimation, and positive predictive values (PPV) of CB based subtyping (luminal A vs. B) were calculated.
Results: In SSP 140/220 BCs (64%) were luminal A, 80 (36%) were luminal B. The agreement between CB and OP was 77% (169/220). Overestimation of proliferation in CB occurred in 10 (4%) and underestimation in 41 (19%) cases. The PPVs of CB based Ki67-LI for luminal A and luminal B were 0.76 (130/171) and 0.79 (39/49), respectively.
Conclusion: The agreement of CB and SSP based subtyping of luminal BCs is generally high. However, underestimation of proliferation in CB may result in subtype misclassification in almost one fifth of luminal Her2 negative luminal tumours.
Citation Format: Cornelia M Focke, Thomas Decker. Ki67-labelling index of luminal breast cancers: Agreement of core biopsy and surgical specimen results [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-09.
Abstract P5-04-10: Characterization of the immune infiltrate in HER2+ breast cancer
Authors: Ganesan Shridar , Alexe Gabriela , Hirshfield Kim M , Yao Ming , Bhanot Gyan , Deborah Toppmeyer 
Published: May 2015

Abstract
A subset of HER2+ breast cancer is characterized by high expression of lymphocyte-associated genes and the presence of a robust, histologically apparent, lymphocytic infiltrate. The presence of an immune signature and lymphocytic infiltration is associated with improved outcome, and may be a marker of improved response to trastuzumab-based therapy. The relationship of the immune signature in these cancers to the biology and functional status of the lymphocyte subsets present in the tumor microenvironment remain unclear. To better characterize the immune microenvironment of HER2+ cancers, we have analyzed paired RNA sequencing data and histologic image data from The Cancer Genome Atlas. We have confirmed the presence of a strong immune signature in a subset of HER2+ breast cancers that is correlated with the presence of a robust lymphocytic infiltrate. Immuno-phenotyping of the lymphocytic infiltrate was performed on an independent set of HER2+ breast cancers from the Rutgers Cancer Institute of New Jersey. CD8+ T-cells and macrophages are a significant component of the immune infiltrate in these cancers. Interestingly, CD20+ B-cells were also present in the tumor stroma as large aggregates whose organization is suggestive of the presence of ectopic germinal centers. The relationship of lymphocyte subsets present in HER2+ breast cancer, immunoglobulin subtypes expressed and correlation with immune checkpoint protein expression will be presented. The composition of the immune infiltrate and its organization into ectopic germinal centers may give new insight into the role of the immune microenvironment in the development of HER2+ breast cancer and the response to trastuzumab.
Citation Format: Shridar Ganesan, Gabriela Alexe, Kim M Hirshfield, Ming Yao, Gyan Bhanot, Toppmeyer Deborah. Characterization of the immune infiltrate in HER2+ breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-04-10.
Abstract P5-05-10: Leptin peptide receptor antagonist linked to nanoparticles: A novel adjuvant therapy for triple negative breast cancer
Authors: Harmon Tia L , Harbuzariu Adriana , Dill Courtney D , Yang Lily , Gonzalez-Perez Ruben R 
Published: May 2015

Abstract
Background: Obesity and high leptin levels are strongly associated with breast cancer, relapse, drug resistance, and poor patient outcomes. Over expression of leptin and its receptor, Ob-R, induce cell proliferation, angiogenesis, and metastasis in Triple Negative Breast Cancer (TNBC). This aggressive form of the disease has no targeted therapy and chemotherapeutics show several undesirable side effects. We have created a Leptin Peptide Receptor Antagonist, LPrA2, which has been shown to effectively prevent leptin signaling. LPrA2 was coupled to iron oxide nanoparticles (IONPs) and used to determine its potential use as an adjuvant to chemotherapeutics.
Methods: IONPs, bound to LPrA2, were confirmed by Western Blot. TNBC cells were then treated with IONP-LPrA2 plus Cisplatin, Doxorubicin, Paclitaxel, Cyclophosphamide, and Sunitinib. Subsequently, the TNBC cells were analyzed for proliferation, cell cycle progression, and apoptosis with the Cellometer Vision Image Cytometer ®.
Results: IONP-LPrA2 was found to cause a greater decrease in DNA synthesis during the S phase of the cell cycle in TNBC cells than LPrA2 alone. Additionally, IONP-LPrA2 when combined with chemotherapeutics or anti-angiogenic drugs showed synergistic effects on cell proliferation and apoptosis.
Conclusion: These findings indicate that IONP-LPrA2 may be useful in the prevention and treatment of TNBC. Further IONP-LPrA2 treatment may increase the efficiency of chemotherapeutics. These results could be particularly relevant for obese patients, whom show high incidence and the poorest outcome of TNBC.
Acknowledgements: This work was partially supported by the National Institutes of Health and National Cancer Institute Grant 1SC1CA138658-05 and U54 CA118638, and DOD Idea Award BC 123427 to RRGP; and facilities, and support services at Morehouse School of Medicine (NIH RR03034 and 1C06 RR18386) and NIH/NCRR grant 1G12RR026250-03.
Citation Format: Tia L Harmon, Adriana Harbuzariu, Courtney D Dill, Lily Yang, Ruben R Gonzalez-Perez. Leptin peptide receptor antagonist linked to nanoparticles: A novel adjuvant therapy for triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-05-10.
Abstract P5-06-05: miRNAs associated with DNA repair capacity in Puerto Rican women with breast cancer
Authors: Matta Jaime , Isaza Clara , Ortiz Carmen , Suarez Erick , Morales Luisa 
Published: May 2015

Abstract
BACKGROUND: MicroRNAs (miRNA) are short non-protein-coding RNAs that regulate gene expression at the post-transcriptional level via binding to 3′-untranslated regions of protein-coding transcripts. Some miRNAs have been used as diagnostic, prognostic and therapeutic markers of breast cancer (BC). It is well established that dysregulation of DNA repair capacity (DRC) is an important risk factor of BC. However, there is little published information as to what specific miRNAs are associated with DRC in women with BC. OBJECTIVE: The main objective of this study was to identify candidate miRNAs associated with dysregulation of DRC in women with BC. METHODS: Plasma samples from 30 BC cases and 30 controls selected based on their DRC levels (low, high) using a proprietary algorithm. Samples were analyzed for miRNA expression utilizing protocols from Applied Biosystems (Life Technologies). The miRNA expression profiling was performed utilizing the RT-PCR TaqMan Array Human MicroRNA A Cards v 2.0 (Applied Biosystems) containing 383 miRNA probes. Single-stranded cDNA was synthesized from 200 ng of total RNA in 8 Multiplex RT primer pool reactions containing stem-looped RT primers that were specific to mature miRNAs. U6 snRNA-001973 was selected for normalization based on our own experimental validations. To quantify the association of the miRNA expression the fold change () was estimated for every detector with the p-values calculated using the t-test. RESULTS: Candidate miRNAs that showed a statistically significant expression were: miR-146, miR-34a, miR-221, Let-7b, miR-193b, miR-132, miR-192, miR-21, miR-197, miR-24, miR-26b, miR-29c were identified based on a false discovery rate of 4%. The results showed that twelve miRNAs differentially expressed in patients with BC. Candidate miRNAs have been reported associated with the expression of twenty seven DNA repair genes. Two of these genes are part of the NER pathway which has been identified by previous studies as important in BC. CONCLUSION: Our preliminary data suggests that differential expression of specific miRNAs might be associated with dysregulation of DRC in BC. The molecular mechanisms by which miRNAs regulate DNA repair genes remain to be elucidated. However, our results lend further promise to the concept of miRNAs as a tool to study the regulation of DRC. We see potentialfuture applications in prognosis and therapy of women with BC. Supported by grants S06 GM008239-20 and 1SCA157250 from the NCI Center to Reduce Health Disparities and NIH-MBRS Program (NIGMS) and NIH-NIGMS #GM082406 (CO).
Citation Format: Jaime Matta, Clara Isaza, Carmen Ortiz, Erick Suarez, Luisa Morales. miRNAs associated with DNA repair capacity in Puerto Rican women with breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-06-05.