bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-01-31: Validation of novel diagnostic kits using the semi-dry dot-blot method for detecting metastatic lymph nodes in breast cancer; distinguishing macrometastases and micrometastases
Authors: Otsubo R , Hirakawa H , Oikawa M , Inamasu E , Baba M , Matsumoto M , Yano H , Kinoshita N , Abe K , Fukuoka J , Nagayasu T 
Published: March 2017

Abstract
Background: The semi-dry dot-blot (SDB) method is a diagnostic procedure for detecting lymph node (LN) metastases. Metastases are confirmed by the presence of cytokeratin (CK) in lavage fluid of sectioned LNs that contain anti-pancytokeratin antibody, based on the theory that epithelial components such as CK are not found in normal LNs. We evaluated two novel SDB kits that use the newly developed anti-CK19 antibody for diagnosing LN metastases in breast cancer.
Methods: We obtained 159 LNs dissected from 93 breast cancer patients from July 2013 to December 2015 at Nagasaki University Hospital, including 38 dissected axillary LNs and 121 sentinel LNs, sliced at 2-mm intervals and washed with phosphate-buffered saline. The suspended cells in the lavage fluid of sliced LNs were centrifuged and lysed to extract protein. This extracted protein was used with a low-power and a high-power kit to diagnose LN metastasis. The washed LNs were blindly diagnosed by pathologists using hematoxylin and eosin (H&E) stain. Diagnoses based on the kit were compared with their H&E counterparts.
Results: Of the 159 LNs, 68 were assessed as positive and 91 as negative by permanent pathological examination with H&E. Sensitivity, specificity, and accuracy of the low-power kit for detecting LN metastases was 83.8%, 100%, and 93.1%, respectively. In 11 false-negative cases, there were nine micrometastases, producing a sensitivity of 96.4% for detecting macrometastases. Sensitivity, specificity, and accuracy of the high-power kit for detecting LN metastases was 92.6%, 92.3%, and 92.5%, respectively. Combining the low- and high-power kit results, sensitivity, specificity and accuracy for distinguishing macrometastases from micrometastases was 94.5%, 95.2%, and 95.0%, respectively. Diagnosis was achieved in approximately 20 min using the kits, at a cost of less than 25 USD.
Conclusions: The kits in our study were accurate, quick, and cost-effective in diagnosing LN metastases without the loss of LN tissue. The kits' ability to distinguish macrometastases from micrometastases was excellent, which is important, clinically.
Citation Format: Otsubo R, Hirakawa H, Oikawa M, Inamasu E, Baba M, Matsumoto M, Yano H, Kinoshita N, Abe K, Fukuoka J, Nagayasu T. Validation of novel diagnostic kits using the semi-dry dot-blot method for detecting metastatic lymph nodes in breast cancer; distinguishing macrometastases and micrometastases [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-31.
Abstract P2-01-34: Identification and biopsy of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasound (CEUS) in pre-operative breast cancer patients: Early collective experience of the UK Microbubble Group
Authors: Cox KL , Sharma N , Leaver A , Lim A , Mills P , Weeks J , Sever A , Hashem M , DeSilva T 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P2-01-35: A one-day protocol with activities lower than 20 MBq for the detection of sentinel lymph nodes - Experience after 150 cases
Authors: Kolberg H-C , Afsah S , Winzer U , Akpolat-Basci L , Stephanou M , Liedtke C 
Published: March 2017

Abstract
Introduction:
Common protocols for the detection of sentinel lymph nodes (SLN) in early breast cancer often include injection of the tracer one day before surgery. In order to detect enough activity on the day of surgery, the applied activity in many protocols is as high as several hundred MBq. Even in common one-day protocols the activity applied is often up to 50 MBq. We developed a one-day protocol with a mean activity lower than 20 MBq in order to reduce radiation exposure for patients and staff. Here we are presenting our experience after 150 cases.
Material and methods:
150 patients with clinically and sonographically negative axilla (cN0) and no multicentricity underwent a SLN biopsy using a low-dose protocol performed on the day of surgery. After ultrasound-guided injection of the tracer (Technetium99) lymphoscintigraphy was performed in all cases. 7 minutes before the first cut 5 ml blue dye was injected in the region of the areola. Fresh-frozen sections of the SLN(s) were not performed.
Results:
In 149 of 150 patients (99.3%) at least one SLN could be identified by lymphoscintigraphy. The detection rate during surgery with combined tracers Technetium99 and blue dye was 100%. The mean applied activity was 17.8 MBq (9-20). A mean number of 1.3 (0-5) SLNs were identified by lymphoscintigraphy, a mean number of 1.7 (1-5) SLNs were removed during sentinel lymph node biopsy. 36 patients received a secondary axillary dissection according to the historical standard because of involved SLNs. In 11 cases (30.6%) additional involved lymph nodes were found.
Conclusion:
One-day protocols with an activity lower than 20 MBq are a safe alternative to two-day protocols with significantly higher radiation doses. Using Technetium99 and blue dye in a dual tracer approach, detection rates of 100% are possible in clinical routine with minimal radiation exposure for patients and staff. The number of removed lymph nodes, the rate of secondary axillary dissections and the number of cases with additional involved lymph nodes is not higher than in published trials.
Citation Format: Kolberg H-C, Afsah S, Winzer U, Akpolat-Basci L, Stephanou M, Liedtke C. A one-day protocol with activities lower than 20 MBq for the detection of sentinel lymph nodes - Experience after 150 cases [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-35.
Abstract P2-02-03: Optimized prediction of deleterious missense mutations in BRCA1 and BRCA2 genes
Authors: Hart SN , Hoskin T , Shimelis H , Feng B , Lindor NM , Monteiro A , Iversen E , Goldgar DE , Suman V , Couch FJ 
Published: March 2017

Abstract
Approximately 15% of genetic screens for mutations in BRCA1 and BRCA2 identify Variants of Uncertain Significance (VUS). Primarily missense mutations, VUS are often difficult to interpret, leading to either uncertainty in how to properly counsel a patient or an unnecessary prophylactic surgery. Given the paucity of data for which missenses are classified as truly pathogenic, computational deleterious missense prediction (DMP) algorithms are used to predict whether a mutation is likely deleterious or neutral. Accuracy of DMPs can vary considerably and have only been calibrated on a relatively small number of missense mutations of demonstrable effect on protein function. In this study, the performance of 41 different DMPs was compared to functional data from 455 functionally characterized missense variants in BRCA1 and BRCA2. New optimized thresholds for classifying missense mutations as deleterious are presented for several existing models as well as a newly derived naïve voting method (NVM). The areas under the curve estimates for the NVM approach are between 0.889-0.922, much higher than previous methods. We estimate that the overall pathogenic potential of missense variants to be 6.8% for BRCA1 and 3.2% of BRCA2, but can be as high as 50% depending on protein location. Overall these results provide key insights into how to predict deleterious missense mutations in BRCA1 and BRCA2.
Citation Format: Hart SN, Hoskin T, Shimelis H, Feng B, Lindor NM, Monteiro A, Iversen E, Goldgar DE, Suman V, Couch FJ. Optimized prediction of deleterious missense mutations in BRCA1 and BRCA2 genes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-02-03.
Abstract P2-02-04: Li-Fraumeni syndrome in females with early onset breast cancer in a Mexican population
Authors: Gallardo-Alvarado LN , Cantu-De Leon DF , Tusie-Luna T , Tusie-Luna I , Diaz-Chavez J , Herrera EM , Chavez-MacGregor M , Bargallo-Rocha E , Villarreal C , Herrera.Montalvo LA , Segura-Kato YX 
Published: March 2017

Abstract
Background: Breast cancer in Mexican patients presents in average 10 year earlier compared to other populations. Among patients with TP53 mutations, breast cancer is the most common malignancy. In this study we aim to determine the rate of TP53 mutations among young Mexican breast cancer patients.
Methods: Breast cancer patients younger that 45 were retrospectively identified, only patients without BRCA1/2 mutations were included. Clinical records and pedigrees were reviewed. Next generation sequencing test for TP53 was performed from blood specimens. All pathogenic mutations were confirmed by Sanger sequencing and verified if were included in the IACR TP53 database.
Results: Among the 78 patients younger than 45yo evaluated and tested with next generation sequencing, we identified 5 patients with a TP53 mutation (6.4%). All were younger than 36 corresponding to a rate of 9.4% of mutations in this group of individuals (n = 53). Two, not previously described, frameshift mutations were found (c.291delC and c.273dupG) and three missense mutations (c.844C&gt;T, c.517G&gt;A, c.604C&gt;T). A VUS c.672G&gt;A that causes a silent mutation in a splicing-donor site was identified. All patients with a TP53 mutation had locally advanced disease and tumors were high grade and Her2 positive.
Conclusions: Among Mexican women younger than 45yo, the rate of TP53 mutations was higher than in other populations where it's estimated to be 1%. Among patients younger than 36 the proportion was even higher. All patients had a family history suggestive of Li-Fraumeni syndrome. The VUS found in our series needs a deeper analysis (family segregation, structure and function of the resulting protein). Our results support the international recommendation of performing molecular testing for TP53 in breast cancer patients younger than 35 years. Identification of patients with TP53 mutation has important prognostic, therapeutic and quality of life implications for the proband in addition of the risk reduction strategies and intensive surveillance recommended in their families.
Citation Format: Gallardo-Alvarado LN, Cantu-De Leon DF, Tusie-Luna T, Tusie-Luna I, Diaz-Chavez J, Herrera EM, Chavez-MacGregor M, Bargallo-Rocha E, Villarreal C, Herrera.Montalvo LA, Segura-Kato YX. Li-Fraumeni syndrome in females with early onset breast cancer in a Mexican population [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-02-04.
Abstract P2-03-11: Genomic pattern of breast carcinomas carrying mutations of non-BRCA homologous recombination genes
Authors: Lin P-H , Kuo W-H , Wang M-Y , Lo C , Lin C-H , Lu Y-S , Chiu C-F , Huang C-S 
Published: March 2017

Abstract
Background
BRCA1 and BRCA2 are involved in the homologous recombination (HR) double-strand DNA break repair and genomic patterns of breast tumors with defective BRCA are characterized by increased genomic instability. The pre-clinical and clinical studies show that tumors with defective BRCA or other HR genes can response to platinum and PARP inhibitors. However, the genomic pattern of tumors carrying mutations of non-BRCA HR genes are not investigated.
Methods
Genomic patterns of breast carcinomas were performed by comparative genomic hybridization (CGH) array containing 60000 probes covering the whole genome with an average spacing of 40kb. The frequency of gains and losses for each regions detected by probes was calculated by ratio thresholds of 0.25 and -0.25, respectively. Large-scale genomic structural aberration was defined as the region of gains and losses of at least 10Mb. We analyzed the difference of large-scale aberration, including numbers, length and specific regions, between tumors with BRCA mutation (mtBRCA), non-BRCA HR mutation (mtHR) and wild type.
Results
We examined 41 breast carcinomas, including 15 cases with BRCA mutations, 14 with non-BRCA HR gene mutations and 12 without mutations (control). The 14 non-BRCA HR gene were 1 ATM, 1 BRIP1, 1 BARD1, 1 FANCA, 2 FANCB, 1 FANCI, 1 PALB2, 2 RAD50, 2 RAD51C and 2 RAD51D. The number and length of large-scale genomic structural aberration of mtBRCA tumors were significantly higher than wild type tumors (number p=0.005; length p=0.005), indicating CGH can distinguish the mtBRCA from control tumors. We then checked the mtHR tumors, which also revealed significantly increased number and longer length of structural aberrations compared to wild type tumors (number p=0.035; length p=0.022), but were not different from mtBRCA tumors (number p=0.204; length p=0.425). Among the specific regions on chromosomes, mtBRCA and mtHR tumors contained similar genomic aberration regions but different from wild type tumors. The most frequent aberration regions of mtBRCA and mtHR tumors are chromosome 6p22.1-p25, 6q21-q27, 8q11.1-q24, 11p11.2-p14.1, 11q, 12p and 19p, which are less revealed in the wild type (all p value &lt;0.05).
Conclusions
Our study demonstrated a direct evidence that increased genomic instability were the common characteristics of mtBRCA and non-BRCA mtHR tumors. In addition, we identify the specific genomic patterns of mtBRCA and mtHR tumors, which can be a biomarker indicating HR deficiency and response to platinum and PARP inhibitors.
Citation Format: Lin P-H, Kuo W-H, Wang M-Y, Lo C, Lin C-H, Lu Y-S, Chiu C-F, Huang C-S. Genomic pattern of breast carcinomas carrying mutations of non-BRCA homologous recombination genes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-03-11.
Abstract P2-04-24: Changes of tumor-infiltrating lymphocytes and programmed death-ligand1 positivity after neoadjuvant chemotherapy in patients with locally advanced breast cancer
Authors: Choi YJ , Lee JH , Moon SY , Choi JY , Jung SP , Bae JW , Park KH 
Published: March 2017

Abstract
Background
Recently, the balance in immune system between immune surveillance and tolerance is known to be associated with the prognosis of breast cancer patients. The aim of this study was to investigate changes of tumor-infiltrating lymphocytes (TILs) and programmed death-ligand1 (PD-L1) status after neoadjuvant chemotherapy (NAC) and their impact on recurrence in patients with locally advanced breast cancer.
Methods
Paired samples (before and after NAC) of triple negative or HER2+ breast cancer tissue were obtained from clinical stage II or III patients (n=39) undergoing NAC and subsequent breast resection. The assessment of immunohistochemical (IHC) staining for PD-L1 were performed. Immunostaining of forkhead box P3 (Foxp3) and CD4/CD8 were performed for subtyping of TILs in triple negative breast cancer (TNBC) only. Clinicopathologic data including baseline characteristics, tumor response and recurrence were reviewed.
Results
Proportion of PD-L1 (+) tumor cells in pre-chemotherapy tissue was 20% (5/25) in HER2+ and 28.6% (4/14) in TNBC. It could not predict pathologic complete response. Most post-chemotherapy tissue (21/24) showed same PD-L1 positivity with pre-chemotherapy tissue. The rest showed the decreased PD-L1 positivity after NAC.
In cases of TNBC, the increased number of CD8+ T cells was significantly associated with PD-L1 positivity in pre-chemotherapy tissue. (p=0.001) Foxp3+ T cell proportions decreased significantly (p=0.046) and CD8+/Foxp3+ T-cell ratio increased significantly (p=0.023) after NAC. The patients with increased number of CD8+ T cells after NAC had a tendency to live longer without recurrence compared to patients with decreased CD8+ T cells (62.3 vs 38.1 months, p=0.158).
Conclusion
Our data provides the clinical evidence that PD-L1 positivity are associated with CD8+ T cell proportion and increased CD8+ T cells after NAC might be good prognostic marker. The role of immunologic balance as a prognostic marker for recurrence must be evaluated in future study.
Citation Format: Choi YJ, Lee JH, Moon SY, Choi JY, Jung SP, Bae JW, Park KH. Changes of tumor-infiltrating lymphocytes and programmed death-ligand1 positivity after neoadjuvant chemotherapy in patients with locally advanced breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-24.
Abstract P2-04-26: Identifying patient-specific neoepitopes for cell-based and vaccine immunotherapy across breast cancer classifications reveals rarely shared recurrent neoepitopes
Authors: Nguyen A , Sanborn JZ , Vaske CJ , Rabizadeh S , Niazi K , Soon-Shiong P , Benz SC 
Published: March 2017

Abstract
Introduction: Targeted therapies for breast cancers such as trastuzumab and everolimus have durable clinical benefits for patients that express the relevant biomarkers (HER2 and mTOR respectively). Triple negative breast cancer patients lack these biomarkers and are left with few options. Recent advances in immunotherapy agents against PD-1/CTLA4 for patients with melanoma have yielded amazing clinical benefits for a subset of patients and may have similar results in breast cancer patients, but again the vast majority of patients still undergo disease progression. We analyzed whole genome sequencing (WGS) and RNA sequencing data from The Cancer Genome Atlas (TCGA) to identify neoepitopes among breast cancer patients that could be used to develop next-generation, patient-specific cancer immunotherapies. Neoepitopes are tumor specific markers that arise from mutations acquired from cancer and may represent a path to targeted therapies even in triple negative breast cancers.
Results: We analyzed 99 breast cancer patients from TCGA, containing a mixture of PR+/HER2+/ER+ and TNBC classifications. These breast cancer patient samples were selected by the availability of whole genome sequencing (WGS) data, RNA-sequencing data as well as clinical outcome data. We identified an average of 680 potential neoepitopes per patient based solely on WGS data. To further refine and select high quality neoepitopes we restricted these neoepitopes based on gene expression yielding an average of 304 expressed neoepitopes per patient. We predicted each patient's HLA typing using only omics data, which we then used to predict HLA-expressed neoepitope binding analysis resulting in an average of 11 high-quality tumor specific neoepitopes per patient. We identified few recurrent neoepitopes that were bound and expressed, indicating the need for a personalized medicine approach.
Conclusions: Within the TCGA dataset, the majority of neoepitopes among patients with breast cancer were unique to each patient. Rarely within subsets of breast cancers such as HER2+, we identify neoepitopes that are shared between patients. For breast cancer patients who do not respond to targeted therapies, high-throughput identification of neoepitopes could serve as the basis for the development of next-generation, patient-specific immunotherapies.
Citation Format: Nguyen A, Sanborn JZ, Vaske CJ, Rabizadeh S, Niazi K, Soon-Shiong P, Benz SC. Identifying patient-specific neoepitopes for cell-based and vaccine immunotherapy across breast cancer classifications reveals rarely shared recurrent neoepitopes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-26.
Abstract P2-05-22: Prognostic significance of nuclear factor kappa B in node-negative breast cancer is most pronounced in luminal B breast cancer
Authors: Schmidt M , Madjar K , Heimes A-S , Battista M , Lebrecht A , Almsetdt K , Hasenburg A , Rahnenführer J , Hengstler JG 
Published: March 2017

Abstract
Background: The importance of the cellular as well as the humoral immune system is increasingly recognized in breast cancer. The transcription factor nuclear factor kappa B (NFKB1) plays an important role in immune cell development. We examined the prognostic significance of NFKB1 in node-negative breast cancer.
Methods: Microarray based gene-expression data for NFKB1 (209239_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Intrinsic subtypes were determined using gene-expression data. Prognostic significance of NFKB1 for metastasis-free survival (MFS) was examined in the whole cohort, in estrogen receptor (ER) positive as well as ER negative patients, and in different intrinsic subtypes: luminal A, liminal B, basal-like, HER2-enriched (HER2-E), and normal-like. Independent prognostic relevance was analysed using multivariate Cox regression.
Results: Higher RNA expression of NFKB1 was related to better MFS in a meta-analysis of the whole cohort (HR 0.48, 95% CI 0.34-0.67, P&lt;0.0001). NFKB1 was significantly associated with MFS only in ER positive (HR 0.41, 95% CI 0.24−0.69, P=0.0008) but not in ER negative (HR 0.76, 95% CI 0.39−1.48, P=0.4245) patients. Regarding intrinsic subtypes, the prognostic significance of NFKB1 was most pronounced in luminal B breast cancer (HR 0.40, 95% CI 0.17−0.93, P=0.0338) as compared to luminal A (HR 0.67, 95% CI 0.16−2.73, P=0.5738), basal-like (HR 0.67, 95% CI 0.29−1.56), P=0.3484), HER2-E (HR 0.70, 95% CI 0.25−2.00, P=0.5083), and normal-like (HR 0.49, 95% CI 0.18−1.32, P=0.1579) breast cancer. However, NFKB1 failed to show independent prognostic significance (HR 0.72, 95% CI 0.42-1.24, P=0.235) in multivariate analysis. Only histological grade of differentiation (HR 2.06, 95% CI 1.27-3.35, P=0.003) and tumor size (HR 1.58, 95% CI 1.01-2.48, P=0.045), but neither age nor HER2 status nor hormone receptor status maintained an independent prognostic association with MFS.
Conclusions: The transcription factor NFKB1 shows prognostic significance in node-negative breast cancer. Higher expression of NFKB1 is associated with improved outcome. The prognostic impact of NFKB1 differs between intrinsic subtypes and is most pronounced in luminal B breast cancer.
Citation Format: Schmidt M, Madjar K, Heimes A-S, Battista M, Lebrecht A, Almsetdt K, Hasenburg A, Rahnenführer J, Hengstler JG. Prognostic significance of nuclear factor kappa B in node-negative breast cancer is most pronounced in luminal B breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-22.