bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-01-24: S100A11 is a diagnostic marker and promotes cancer progression for luminal breast cancer
Authors: Kwong A , Wang J , Chen J , Siu MT , Chuek I , Shin V 
Published: May 2019

Abstract
Background: S100A11, also known as calgizzarin, is a member of S100 calcium-binding protein family and is upregulated in various cancers including lung cancer, renal cell cancer, ovarian cancer and pancreatic cancer. Many studies have shown that S100A11 is related to cancer progression. However, the function of S100A11 in breast cancer remains largely unknown. In the present study, we aim to investigate the underlying mechanism(s) of S100A11 in cancer cell proliferation, invasion, migration, and evaluate the clinical association with breast cancer.
Methods: The mRNA expression level of S100A11 in plasma samples from breast cancer patients and normal control individuals was detected with quantitative real-time PCR. Knockdown of S100A11 using small interfering RNA (siRNA) in luminal breast cancer cells (MCF-7 and T-47D) were used to study the biological function of S100A11 for the progression of breast cancer. Cell proliferation ability was analysed with MTT assay and colony formation assay. Cell invasion ability was analysed with transwell invasion assay. Cell migration ability was detected by wound healing assay. Cell cycle distribution and apoptosis were determined by flow cytometry.
Results: The mRNA expression level of S100A11 was significantly increased in the plasma samples obtained from 182 breast cancer patients compared with 115 normal control individuals, and the area under curve was 0.83. In particular, higher expression was associated with luminal breast cancer subtype as well as respective cell lines. S100A11 siRNA effectively inhibited the proliferation, invasion, and migration abilities of MCF-7 and T-47D cells. Knockdown of S100A11 caused cell cycle G1 arrest and induced apoptosis. Silencing of S100A11 decreased the mRNA and protein expression levels of cyclin D1 and NF-κB p50 whereas increased the expression level of E-cadherin in MCF-7 and T-47D cells.
Conclusion: These results suggest that S100A11 is upregulated in breast cancer and promoted cell proliferation, invasion and migration in MCF-7 and T-47D cells through the upregulation of NF-κB p50 and cyclin D1. Thus, S100A11 may be a potential diagnostic marker for luminal breast cancer subtype and also a therapeutic target for breast cancer.
Citation Format: Kwong A, Wang J, Chen J, Siu MT, Chuek I, Shin V. S100A11 is a diagnostic marker and promotes cancer progression for luminal 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 P4-01-24.
Abstract P4-03-05: Not presented
Authors: Carraro DM , Palmero EI , Galvao HC , Berra CM , Brianese RC , Torrezan GT , da Cruz Formiga MN , de Lima FT , Fernandes GC , de Paula AE , Michelli RD , Gutierrez Barrera AM , Arun BK 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Carraro DM, Palmero EI, Galvao HC, Berra CM, Brianese RC, Torrezan GT, da Cruz Formiga MN, de Lima FT, Fernandes GC, de Paula AE, Michelli RD, Gutierrez Barrera AM, Arun BK. 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 P4-03-05.
Abstract P4-03-08: Analyzing the clinical actionability of germline CYP2D6 polymorphism in Chinese breast cancer population
Authors: Huang L , Cao A 
Published: May 2019

Abstract
Background:Tamoxifen is effective for endocrine-responsive breast cancer as adjuvant therapy. CYP2D6 enzyme metabolizes tamoxifen to clinically active metabolites, while CYP2D6 polymorphisms may adversely affect tamoxifen efficacy by some retrospective clinical evidence. This study was carried out to estimate genotype frequencies of common variants of CYP2D6 in Chinese population. The relationship between prescription of selective estrogen receptor modulators (SERMs) and CYP2D6 polymorphism was also analyzed.
Methods: This was a retrospective research of early-stage patients who underwent surgical treatment at Fudan University Shanghai Cancer Center with ER+ and/or PR+ breast cancer. Genomic DNA was extracted from peripheral blood, which was used for genotyping CYP2D6*10 (C100T) single-nucleotide polymorphisms by polymerase chain reaction-based methods.
Results: A total of 312 patients with primary breast cancer were identified. More than 90.0% patients were in premenopausal status. The allele frequence of CYP2D6*10 in the Chinese population was 54.3%. The genotype frequencies of CYP2D6*10 were 20.5%, 50.3%, 29.2%, for wild-type, heterozygous and homozygous type respectively. We also found this SNP had no significant correlation with clinical characteristics. 145 patients were continuing endocrine treatment in first 5 years. 34.5% patients received CYP2D6 polymorphism test before the prescription of SERMs. The results significantly effected the choice of SERMs. Only 6.2% homozygous type patients took tamoxifen, 45.5% heterozygous patients chose tamoxifen, while 75.0% for wild type. 65.5% patients received CYP2D6 polymorphism test during the treatment of tamoxifen. 63.9% homozygous type patients switched to Toremifene, while 18.9% heterozygous patients changed the endocrine treatment.
Conclusions: The results showed that the frequence of CYP2D6*10 allele was high and nearly 30% Chinese breast cancer population were intermediate metabolizer for tamoxifen. The cyp2d6 polymorphism would influence prescription of SERM in premenopausal breast cancer patients. Patients with homozygous types should take other endocrine treatment instead of tamoxifen, which need more evidence of prospective clinical trials.
Citation Format: Huang L, Cao A. Analyzing the clinical actionability of germline CYP2D6 polymorphism in Chinese breast cancer population [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 P4-03-08.
Abstract P4-04-08: Genomic profiling of 304 treatment-naïve Chinese breast cancer patients: A comparison of Chinese and TCGA cohorts
Authors: Liao N , Zhang G , Wang Y , Guo L , Cao L , Zhang Z , Balch CM , Meric-Bernstam F 
Published: May 2019

Abstract
Background: The complexity of BC at the clinical, morphological and molecular level has been well recognized. Molecular profiling, which reveals the intrinsic biology among subtypes, has significantly advanced the management of this disease. However, previous studies have provided very limited molecular data on Chinese breast cancer patients.
Methods: We performed targeted sequencing using a panel consisting of 36 BC related genes to interrogate the genomic landscape of 304 consecutive treatment-naïve Chinese BC patients and compared our results to the TCGA data set.
Results: Comparing to TCGA, our cohort had significantly fewer patients with triple negative breast cancer (8.2% vs 15.5% p=0.002). The most prominent genomic difference was our cohort had significantly higher TP53mutation frequency in HR+/HER2- and HR+/HER2+ groups. The composition of TP53 mutations also differed significantly between two cohorts in HR+/HER2- group, with TCGA cohort having missense mutation as the predominant mutation; whereas, in our cohort, nonsense and frameshift mutations were predominant. We classified the most populated and diverse group of HR+/HER2- cancer into 4 subgroups based on molecular signature. The clinical significance of this proposed classification was confirmed by differences in overall survival using data from the TCGA.
Conclusions:We identified distinctive genomic patterns associated with Chinese breast cancer patients compared to TCGA data, suggesting the importance of mutation-based stratification according to ethnic status. To the best of our knowledge, this is one of the largest study of Chinese BC patients that interrogated the spectrum of mutational events and correlated these molecular signatures with clinical outcomes.
This study was supported by funding from National Natural Science Foundation of China (Grant No. 81602645), Guangdong Provincial Natural Science Foundation (Grant No. 2016A030313768) and Research Funds from Guangzhou Science and Technology Bureau (Grant No. 201707010418 and 201804010430).
Citation Format: Liao N, Zhang G, Wang Y, Guo L, Cao L, Zhang Z, Balch CM, Meric-Bernstam F. Genomic profiling of 304 treatment-naïve Chinese breast cancer patients: A comparison of Chinese and TCGA cohorts [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 P4-04-08.
Abstract P4-04-10: Genomic profiling of multifocal breast cancer reveals inter-lesion heterogeneity
Authors: Ahn S , Kim HJ , Kang E , Kim E-K , Kim SH , Kim JH , Kim IA , Park SY 
Published: May 2019

Abstract
Introduction: Multifocal breast cancers are common, and tend to show more aggressive clinical features than unifocal breast cancers. While each foci of multifocal breast cancers with similar histology shares the same hormone and ERBB2 receptor status in most cases, substantial genomic differences among lesions have been reported. We aimed to investigate the potential genomic differences between multifocal breast cancer lesions.
Materials and methods: Twenty-one patients with multifocal breast cancer documented in the resection specimen were included. We selected two lesions with the same histology from each of these 21 patients. Capture-based targeted next generation sequencing was performed using a cancer gene panel consisting of 170 genes for single nucleotide variants (SNV) and small insertions/deletions (Indel), and copy number alterations.
Results: The most frequent mutation was TP53 (38.1%), followed by PIK3CA (28.6%). Pathogenic mutations (SNV and Indel) were detected in 13 of 21 patients, of whom 11 shared oncogenic variants in the two lesions. The remaining two patients had different mutation results in TP53 and PIK3CA, respectively. Genomic heterogeneity of copy number alteration was observed in 6 (28.6%) of 21 patients, including difference of FGFR1 status in two patients and difference of FGFR2 status in one patient.
Conclusion: Despite similar histologic features of multifocal tumors, genomic inter-lesion heterogeneity was identified in about one-fourth of patients. The spatial genomic heterogeneity in multifocal breast cancers needs to be considered in representative sampling and molecular tests for personalized medicine.
Citation Format: Ahn S, Kim HJ, Kang E, Kim E-K, Kim SH, Kim JH, Kim IA, Park SY. Genomic profiling of multifocal breast cancer reveals inter-lesion heterogeneity [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 P4-04-10.
Abstract P4-04-11: A small amount of primary breast cancer shows high tumor mutation burden that may benefit from immune checkpoint inhibitor therapy
Authors: Wang J , Chen W , Jiang Z , Lin X , Qin T , Yang X , Liu T , Hu H , Li Z , Xie D , Yao H , Song E 
Published: May 2019

Abstract
Background: Targeted therapy using immune checkpoint inhibitors (ICIs) is a major breakthrough in cancer treatment in the last decade. ICIs like PD1 or PD-L1 antibodies have been shown to be quite effective in cancer like melanoma. However, in most other tumor types including breast cancer, the situation is not as optimistic. Only a small percentage of those patients respond to ICIs therapy. This highlights the importance of identifying biomarkers to predict which patients may benefit from such treatment. Tumor Mutation Burden (TMB) has been shown to be a sensitive marker for ICI treatment. This study is to investigate whether TBM could be used as a biomarker for breast cancer treatment.
Methods: We reviewed next generation sequencing studies of breast cancer. Two such studies with raw data provided were included in our analysis. One study entitled METABRIC performed targeted sequencing of 173 cancer-related genes in around 2500 primary breast cancer tissues. The other study was from TCGA breast cancer project, which performed Whole Exome Sequencing (WES) of around 1000 primary breast cancer samples. Mutation data were downloaded from public data deposit. The number of mutations per sample was calculated. TBM was calculated by divide the coverage in million base pair from that of the total mutation counts.
Results: In METABRIC study, 17272 mutations were identified in 2369 samples, with a median of 7 mutations per sample (95% CI: 6 ˜ 7). The median TMB of METABRIC dataset was 5.8 SNVs/Mb (95% CI: 5 ˜ 5.8). Totally 30 out 2369 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb. In another cohort from TCGA breast cancer study using WES technology, 90172 mutations were identified in 977 samples, with a median of 44 mutations per sample (95% CI: 39 ˜ 50). The median TMB was 1 SNVs/Mb (95% CI: 0.9 ˜ 1.1). Totally 13 out 977 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb.
Conclusions: Breast cancer shows middle to low mutation burden compared to other cancer types. Around 1.3% of breast cancer has quite high TMB of at least 20 SNVs/Mb, which may be qualified for immune checkpoint inhibitors therapy. Our study indicates that TMB may be incorporated as a standard test for late stage breast cancer patients in the clinical practice.
Keywords: Breast cancer, Tumor Mutation Burden, Whole exome sequencing, Targeted sequencing, Immune checkpoint
Citation Format: Wang J, Chen W, Jiang Z, Lin X, Qin T, Yang X, Liu T, Hu H, Li Z, Xie D, Yao H, Song E. A small amount of primary breast cancer shows high tumor mutation burden that may benefit from immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-04-11.
Abstract P4-06-15: Role of B lymphocytes and B cell-produced IL-27 in breast cancer progression and drug resistance
Authors: Yan H , Viswanadhapalli S , Fernandez M , Rivera C , Sareddy G , Casali P , Vadlamudi R 
Published: May 2019

Abstract
How host immune elements, particularly B cells, are hijacked to promote breast cancer (BCa) tumor progression and acquisition of resistance to current endocrine therapies remain largely unclear. Prompted by our recent findings that B cells are a major source of cytokine IL-27 (the heterodimer of IL-27p28 and EBI3), which regulates many immune functions as both a pro-inflammatory and anti-inflammatory cytokine, as well as the high expression of IL-27 receptor genes in the breast, elevated circulating IL-27 in BCa patients and the association of increased IL-27p28 expression with reduced survival in BCa patients overall and ER+ BCa patients after endocrine therapies, here we hypothesize that B cells promote BCa tumor progression and drug resistance and do so by producing IL-27. In C57 mice transplanted with ERa+ E0771 syngeneic medullary breast adenocarcinoma cells, deficiency in B cells in mMT mice resulted in virtually abolished tumor growth, resulting from significantly high tumor cell death. Remarkably, in residual tumors developed in mMT mice after transplantation with a higher load of E0771 cells, B cells, which were absent in the blood and lymph nodes, were accumulated within tumors – at an even higher frequency than that in wildtype C57 mice – and expressed IL-27. Further, like class-switching B cells that respond to IL-27 produced by neighboring B cells to express an IFNg-induced gene signature in the secondary lymphoid organ during the antibody response, a distinct population of tumor-infiltrating B cells expressed high levels of PD-L1, which could be induced by IL-27 in many immune cell types, including B cells, and several cancer cell types. Finally, IL-27 promoted the growth MCF-7 human BCa cells in the presence of tamoxifen in vitro, consistent with a role of B cell-produced IL-27 in the acquisition of drug resistance by BCa. These, together with the delayed tumor growth in mixed bone marrow chimeric mice with B cell-specific deficiency in IL-27 production, outline a potential role of B cell-produced IL-27 in BCa progression and drug resistance through both BCa cell-intrinsic mechanisms and induction of PD-L1+ B regulatory cells that participate in the immune checkpoint in BCa.
Citation Format: Yan H, Viswanadhapalli S, Fernandez M, Rivera C, Sareddy G, Casali P, Vadlamudi R. Role of B lymphocytes and B cell-produced IL-27 in breast cancer progression and drug resistance [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 P4-06-15.
Abstract P4-06-18: Withdrawn
Authors: Dunbier AK , Hazlett J , Niemi G , Kemp R 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Dunbier AK, Hazlett J, Niemi G, Kemp R. 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 P4-06-18.
Abstract P4-07-11: Investigating the activity of ESR1 allosteric compounds in ER+ breast cancer
Authors: Uwimana A , Tiong Yip CL , Das R , Cheng Q , Meredith E , Gaither AL 
Published: May 2019

Abstract
Breast cancer (BCa) is the most frequently diagnosed cancer in women worldwide. Approximately 80% of breast cancer is estrogen receptor positive (ER+) with 74% demonstrating high expression of estrogen receptor alpha (). Thus, current endocrine therapies such as selective estrogen receptor degraders (i.e.- Fulvestrant) or selective estrogen receptor modulators (i.e-Tamoxifen) are involved modulation of ER signaling. However, most patients develop resistance to these drugs, and disease progression is common resulting in metastatic disease. Therefore, targeting alternative sites on the surface of has been proposed as an effective therapy to directly block its activity. In the present study, we investigated putative AF2 compounds that can bind to AF2 allosteric sites and inhibit complex formation and transcription of targetgenes. In the present study, we characterized a series of allosteric compounds using breast cancer cellular assays. MCF7 parental cells were treated with a series of putative allosteric compounds in a seven day CTG cell proliferation assay, and the compound ERX-11 was found to exhibit anti-proliferative activity. Genomic RNA was isolated after overnight treatment with ERX-11 to investigate compounds treatment on the expression of key ER pathway transcription factors via real time PCR. The degradation effect on nuclear ER and cytoplasmic ER after treatment with ERX-11 were assessed via western blots. We successfully characterized a series of putative allosteric compounds with ERX-11 being the only compound that exhibited anti-proliferative activity in both MCF7 parental and LSZ resistant cells. ERX-11 inhibited the activation of ER transcription gene and degradation of nuclear ER. These findings show promising effects of ERX-11 to block the AF2 sites on the binding domain of ERα with potential therapeutics for ER+ breast cancer.
Citation Format: Uwimana A, Tiong Yip CL, Das R, Cheng Q, Meredith E, Gaither AL. Investigating the activity of ESR1 allosteric compounds in ER+ 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 P4-07-11.
Abstract P4-08-14: Invasive micropapillary carcinoma had no difference in prognosis compared with invasive ductal carcinoma: A propensity-matched analysis
Authors: Hao S , Zhao Y-Y , Peng J-J , Yang W-T , Ren F , Yu K-D , Shao Z-M 
Published: May 2019

Abstract
Background: Invasive micropapillary carcinoma (IMPC) is a rare histopathological variant of breast carcinoma and usually performs poor clinical characteristics, such as high tendency of lymph nodes metastases. But whether it has worse prognosis than invasive ductal carcinoma (IDC) is still controversial nowadays. We conducted this retrospective study to figure out the prognostic difference between IMPC and IDC, then guide therapy of IMPC ultimately.
Methods: In this study, we analyzed 327 cases of IMPC patients and 4979 cases of IDC who underwent primary resection in our institution during 2008 to 2012. By using propensity score matching, two groups were matched at a ratio of 1:1 by age, tumor size, nodal status, hormone and HER2 status to demonstrate the difference of prognosis assessed by Kaplan-Meier estimates and Cox regression analysis.
Result: After a mean follow-up of 52 months, we established the IMPC group and figured out 324 IDC patients from the control group by propensity score matching (3 IMPC patients were canceled because of data missing). The result of survival analysis indicated that women diagnosed with IMPC had no significant reduced overall survival (OS) (p = 0.752) and disease-free survival (DFS) (p = 0.578) compared with women with IDC. Multivariate Cox regression analysis revealed that IMPC was not found as an independent prognostic factor for DFS (hazard ratio [HR] = 0.858; 95% confidential interval [CI], 0.419-1.757) or OS (HR = 0.720; 95%CI, 0.353-1.469).
Conclusion: The consequence of survival analysis manifested that there was no statistically significant difference between 2 groups, and elucidated proactive or radical clinical therapy was unnecessary.
Citation Format: Hao S, Zhao Y-Y, Peng J-J, Yang W-T, Ren F, Yu K-D, Shao Z-M. Invasive micropapillary carcinoma had no difference in prognosis compared with invasive ductal carcinoma: A propensity-matched analysis [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 P4-08-14.