bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-08-02: Multi-gene panel testing for hereditary cancer predisposition in unsolved high risk breast and ovarian cancer patients
Authors: Crawford BB , Adams SB , Sittler T , Van den Akker J , Chan SB , Leitner O , Ryan LN , Gil E , Van 't Veer LJ 
Published: March 2017

Abstract
Background
Among women with an elevated risk of hereditary breast and ovarian cancer who previously tested negative for pathogenic mutations in BRCA1 and BRCA2, a subset remain at increased risk of having hereditary breast, ovarian or other cancers, and should be offered multi-gene panel testing. We tested three groups of women who were enrolled in the UCSF Cancer Genetics and Prevention Program: (i) 97 women with a personal history of bilateral breast cancer, (ii) 104 women with a personal history of breast cancer and a first-degree or second-degree relative with ovarian cancer, and (iii) 99 women with a personal history of ovarian, fallopian tube, or primary peritoneal cancer. All women previously tested negative for pathogenic BRCA1 and BRCA2 mutations by either limited or comprehensive testing.
Methods
We performed comprehensive next-generation sequencing using a panel of 19 genes developed by Color Genomics (a CLIA-certified laboratory) covering ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53.
Results
Across the groups tested, 9% had pathogenic mutations in one or more of the genes analyzed (8% in genes other than BRCA1 and BRCA2). Among these women, Ashkenazi Jewish and Hispanic women had elevated mutation rates compared to those of other ethnicities. In addition, we identified two women with pathogenic mutations in two cancer susceptibility genes, which has significant implications for family testing. These results demonstrate the importance of genetic testing of genes other than BRCA1 and BRCA2.
Conclusions
Among women with an elevated risk of hereditary breast and ovarian cancer who have previously tested negative for BRCA1 and BRCA2 mutations, we propose that women with characteristics of any of the three groups above be considered for subsequent multi-gene panel testing. Additionally, ethnicity and the possibility of multiple mutations may be indications for additional testing in these women and in family members of carriers.
Citation Format: Crawford BB, Adams SB, Sittler T, Van den Akker J, Chan SB, Leitner O, Ryan LN, Gil E, Van 't Veer LJ. Multi-gene panel testing for hereditary cancer predisposition in unsolved high risk breast and ovarian cancer patients [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 P3-08-02.
Abstract P3-10-08: Socio-demographic predictors for delay of treatment among a racially diverse, urban breast cancer population
Authors: Ko NY , Patts G , Battaglia TA , Wang C , Denis GV , Hirsch A , Weinberg J 
Published: March 2017

Abstract
Background:
Racial and ethnic disparity in breast cancer outcomes is a long-standing problem that continues to worsen. Recent evidence has underscored the importance of timely care, as delays in treatment can lead to decreased survival. We sought to understand predictors of delay to first treatment among a racially diverse cancer population.
Methods:
This is a retrospective study of breast cancer cases diagnosed between the years 2000 to 2014. Data was extracted from the cancer registry at Boston Medical Center (BMC), an urban safety net hospital. Inclusion criteria were any breast cancer diagnosis from 2000-2014, receiving first treatment at BMC, and disease stage 0-III. Cox Proportional Hazards regression analysis was performed to identify predictors of time to first treatment, defined as days from date of diagnosis to date of first treatment with surgery or neo-adjuvant chemotherapy. Covariates included age, sex, race, type of insurance, marital status, US birth, disease stage and year of diagnosis.
Results:
Patients were 99% female and with a mean age of 58 years (range 23-96). Among a sample of 1545 breast cancer cases, 1372 (89%) had surgery as first treatment and 173 (11%) had neoadjuvant chemotherapy. Median days to treatment was 45 days (IQR 27, 71). In the multi-variable adjusted models for both treatment groups, race, and insurance were significantly associated with delay. In the surgical group, Black race, public or no insurance, non-US born, later stage and unmarried status were associated with increased risk of delay. For example, Blacks were at higher risk for delay (HR= 1.2; 95% CI 1.37-1.04) compared to the Hispanic or White (reference) groups. Public insurance (HR = 1.19; 95%CI 1.37-1.04) and no insurance (HR = 1.43; 95%CI 1.85-1.09) was significantly associated with increased delay when compared to private insurance (reference). In patients with neoadjuvant chemotherapy as first treatment, additional significant predictors of delay were age and year of diagnosis.
Conclusion:
Race and insurance status were significant predictors of delay to first treatment in a population of diverse breast cancer patients seeking care at a safety net hospital. Intervention efforts need to target patients at greatest risk for treatment delays.
Citation Format: Ko NY, Patts G, Battaglia TA, Wang C, Denis GV, Hirsch A, Weinberg J. Socio-demographic predictors for delay of treatment among a racially diverse, urban breast cancer 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 P3-10-08.
Abstract P3-13-23: Predicting residual disease in breast conservative surgery after neoadjuvant treatments in breast cancer patients using the margin index tool
Authors: Rubio IT , Loinaz I , Esgueva-Colmenarejo AJ 
Published: March 2017

Abstract
Background. The appropriate surgical margin after neoadjuvant treatment (NAT) is controversial. Margin index, a relationship of the margin obtained to the size of the tumor, is a reliable method for the prediction of residual disease after breast conservative surgery (BCS) in the adjuvant setting. Our aim was to apply the margin index to patients with BCS after NAT to predict residual disease.
Material and Methods. From a prospectively maintained database, patients with stage I - III with NAT who underwent BCS between July 2008 and December 2012 were included. Margin index was calculated as for the adjuvant setting: margin index = closest margin (mm)/tumor size (mm) × 100 considering the tumor size of the lumpectomy specimen. A receiver operating curve was created using the derived margin index and the presence or absence of residual disease in the re-excision specimen. Patients with pathologic complete response (pCR) (no invasive tumor) were excluded.
Results. Of the 206 patients, 63 (30.5%) had a pCR and were excluded. Of the 143 patients, 76 (53%) had an intraoperative re-excision depending on the surgeon or the intraoperative pathology report. Of the 76 patients, 23 (32%) had residual tumor in the intraoperative re-excision specimen. There were no statistically significant differences in residual disease regardless of who indicates intraoperative re-excision. (p= 0.56) Twenty-three patients (16%) underwent a second surgery for positive or close margins ( &lt; 2mm). Residual disease, whether infiltrating or in situ or both, was found in 10 (43%) patients. The overall c index for the receiver operating curve was 0.76. A margin index &gt; 5 had a sensitivity of 80% and a specificity of 63%.
Conclusion. Rates of re-excision after NAT in BCS patients are similar to the adjuvant setting. Margin index may be a valuable tool for determine residual disease after NAT in patients undergoing BCS. Further validation of this index is warranted in a larger cohort of patients after NAT to confirm these results.
Citation Format: Rubio IT, Loinaz I, Esgueva-Colmenarejo AJ. Predicting residual disease in breast conservative surgery after neoadjuvant treatments in breast cancer patients using the margin index tool [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 P3-13-23.
Abstract P3-14-01: International validation of the EORTC patient-reported outcome measure (PROM) in breast reconstruction (BRR): The EORTC QLQ-BRECON23 evaluating the psychometric properties and clinical effectiveness
Authors: Winters ZE , Afzal M , Rutherford C , Holzner B , Rumpold G , da Costa Vieira RA , Hartnup S , Filcroft K , Bjelic-Radisic V , Oberguggenburger A , Panouilleres M , Mani MR , Catanuto G , Douek M , Kokan J , King MT 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P3-17-02: Gene expression differences between ductal carcinoma in situ with and without progression to invasive breast cancer
Authors: Doebar SC , Sieuwerts AM , de Weerd V , Martens JWM , van Deurzen CHM 
Published: March 2017

Abstract
Background
The mechanism behind progression of ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC) remains unknown. The aim of our study was to increase our understanding regarding molecular alterations driving DCIS progression by comparing gene-expression patterns between patients with pure DCIS and patients with synchronous DCIS and IBC.
Methods
In this retrospective study, we included patients with extensive pure DCIS (n=12), defined as &gt; 5 cm, as a representation of biologically indolent lesions with limited invasive capacity. These cases were matched with patients with a limited DCIS component, defined as &lt; 1 cm, and synchronous IBC (n=12), representing lesions with a high invasive potential. Matching was based on age and surrogate DCIS subtypes. Gene expression profiling, using 93 tumor-specific target genes, was performed to identify transcriptional differences between the DCIS components of these two groups. The identified genes were validated by immunohistochemistry.
Results
In total, for 9 genes there was a significant difference in gene expression between patients with pure DCIS and patients with DCIS and synchronous IBC. The majority of these 9 genes were significantly higher expressed in DCIS samples with IBC, including PLAU (P=0.002), COL1A1 (P=0.006), KRT81 (P=0.009), S100A7 (P=0.015), SCGB1D2 (P=0.023), KRT18 (P=0.029) and NOTCH3 (P= 0.044), while EGFR and CXCL14 showed a significantly higher expression in pure DCIS (P=0.015 and P=0.028 respectively). Based on these 9 genes, unsupervised hierarchical clustering-analysis revealed distinct clustering of patients with pure DCIS and patients with DCIS and synchronous IBC. Immunohistochemical analyses are in progress.
Conclusion
This pilot study suggests that patients with pure DCIS have a significant different gene expression pattern as compared to patients with DCIS and synchronous IBC. If these results can be validated in an independent cohort, these differently expressed genes could be used to predict progression in individual patients diagnosed with DCIS. Furthermore, these genes may pinpoint driver pathway(s) that play an important role in the progression of DCIS to IBC.
Citation Format: Doebar SC, Sieuwerts AM, de Weerd V, Martens JWM, van Deurzen CHM. Gene expression differences between ductal carcinoma in situ with and without progression to invasive 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 P3-17-02.
Abstract P4-02-09: Non-invasive and low-cost technique for early detection of clinically relevant breast lesions using a handheld point-of-care medical device (iBreastExam): Prospective three-arm triple-blinded comparative study for breast cancer screening in low resource setting countries
Authors: Somashekhar SP , Ashwin KR 
Published: March 2017

Abstract
This abstract was not presented at the symposium.
Abstract P4-03-07: Inhibition of cancer-associated fibroblast function by farnesoid X receptor activation: Experimental basis for a novel therapeutic strategy in breast cancer
Authors: Barone I , Vircillo V , Giordano C , Tarallo R , Rinaldi A , Bruno G , Bonofiglio D , Catalano S , Ando' S 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P4-03-16: FAPα (fibroblast activation protein-α) analysis in breast tumor cells and stroma after neoadjuvant treatment
Authors: Calvo I , Prieto M , Suárez-Gauthier A , Pérez FJ , Hernández E , Acosta D , Cárdenas JM , López-Ríos F , Estévez LG 
Published: March 2017

Abstract
Background: FAPα is a transmembrane serine protease expressed on cancer associated fibroblast that promotes tumour growth and invasion. In patients (pts) with poor outcome and survival FAPα is highly overexpressed. FAPα is also expressed in stroma across all breast cancer subtypes without association with clinicopathological factors. Pts without Complete Pathological Response (pCR) after Neoadjuvant Chemotherapy (NC) had poor outcome. We analysed the relationship between the expression of FAPα in stroma (fibroblast) and in epithelial breast cancer cells of pts without pCR after NC (taxanes, antracyclines and trastuzumab in Her2+).
Methods: 60 pts were included. ER, PR and Ki67 were studied by IHQ (Ventana) and Her2 by FISH (PatnVysion). FAPα expression was determined by IHQ (polyclonal, Ventana). St Gallen guidelines for subtype of breast cancer were used.
Results: 53 pts had tissue. Median age 47 years (range 29-68). Median tumour size 43mm and 10 (18.9%) were multifocal. 37 (69.8%) had positive axillary nodes. 47 were ductal invasive carcinomas. 33 (62.3%) were grade 2 and 20 (37.7%) grade 3. 44 pts (83%) had ER+ (20 luminal B), 17 (32%) Her2+ and 6 (11%) triple negative(TN). Median Ki67 was 22% (p25-75:15-38%). Miller-Payne response was 1.9% G1 (1pt), 43.4% G2 (23 pts), 41.5% G3 (22 pts) and 13.2% G4 (7 pts). The recurrences were 2 local and 12 distant (26.4%). Median FAPα in residual epithelial breast cancer cells after NC was 85% (p25-75:30-95%) and in the stroma 20% (p25-75:10-62%). Median epithelial FAPα was 55% in TN, 85% Her2, 72.5% luminal A and 92.5% in luminal B. Median stromal FAPα was 52.5% in TN, 20% Her2, 15% luminal A and 15% in luminal B. There is not association between stromal FAPα and clinicopathological features, but a higher epithelial FAPα was found in tumours wih higher ER, PR and Ki67. In luminal B subtype, stromal FAPα was smaller in pts with relapses (median 7.5%) than without relapses (median 30%). Conclusions: Stromal FAPα in residual cancer after NC is higher in TN breast cancer but without association with relapses in our small sample. However, in luminal B subtype stromal FAPα is smaller in pts with relapses.
Citation Format: Calvo I, Prieto M, Suárez-Gauthier A, Pérez FJ, Hernández E, Acosta D, Cárdenas JM, López-Ríos F, Estévez LG. FAPα (fibroblast activation protein-α) analysis in breast tumor cells and stroma after neoadjuvant treatment [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 P4-03-16.
Abstract P4-07-09: Differential expression of microRNAs (miRNAs) in HER2 negative breast cancer (BC)
Authors: Pascual T , Gámez-Pozo A , Camara-Jurado M , Manso LM , Pérez-Campos A , Trilla L , Fresno-Vara JA , Ciruelos EM 
Published: March 2017

Abstract
Background:
MiRNAs are non-coding single-stranded RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Compared to mRNA signatures, miRNAs have better and stronger biomarker properties with 20 times more power in biomarker studies as compared to mRNAs (when comparing 20,000 mRNAs to ~ 1,000 miRNAs). Global downregulation of miRNAs has emerged as a common theme in human breast tumors and has been shown to contribute to oncogenesis
Hormone receptor (HR) status is one of the most important factors influencing BC outcome. Several data indicate the extensive alterations in miRNAs regulation upon estrogen pathway and suggest the utility of considering miRNAs expression in the understanding the development of cancer disease, invasiveness, metastasis and treatment failure.
Our aim was to identify differential expression miRNAs in HER2 negative BC. We previously reported a set of miRNAs deregulated in HR+/HER2- BC vs. Triple negative BC (TNBC). In this work we have validate these differences in a new cohort of BC patients.
Methods:
Total RNA was extracted samples extracted from primary breast cancer FFPE tissue. MicroRNAs expression was analyzed by RT-qPCR using TaqMan Arrays from Applied Biosystems. Normalization was performed using de DCt method with two housekeeping miRNAs identified previously identified using NorMean. MicroRNA expression values in each group were compared by the Mann Whitney test.
Results:
121 patients with early HER2 negative BC were included in the present study. All patients showed absence of nodal involvement at the time of diagnosis. The median age at diagnosis was 56 years, 89 cases (74%) had positive estrogen receptor and 53 cases (44%) grade 3. miR-20a, miR-19a, miR-106a, miR-18a and miR-135b expression were significantly higher in TNBC samples, whereas miR-190b, miR-375, miR-449a, miR-342, miR-149, miR-193b, miR-214, miR-30a*and miR-30e* were significantly more expressed in ER+/HER2- samples. No significant differences were found in miR-139-5p expression between both groups.
Conclusions:
We have validated fourteen miRNAs that are differentially expressed between ER+/HER2- and TNBC breast cancer subtypes. Altered expression of miRNAs could be a potential therapeutic tool and promising biomarker in personalized treatment.
Citation Format: Pascual T, Gámez-Pozo A, Camara-Jurado M, Manso LM, Pérez-Campos A, Trilla L, Fresno-Vara JA, Ciruelos EM. Differential expression of microRNAs (miRNAs) in HER2 negative breast cancer (BC) [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 P4-07-09.
Abstract P4-08-02: Integration of transcriptomic, proteomic and drug response data in triple negative breast cancer cell lines and PDX models
Authors: Mills CE , Hafner MA , Sorger PK 
Published: March 2017

Abstract
Drug response screens on panels of cell lines aimed at identifying markers of sensitivity or resistance have been limited in their successes. Unfortunately, the recent release of many such studies has been accompanied by concerns surrounding reproducibility. Since then, several publications have addressed these concerns by pointing out sources of variability and by suggesting better experimental methods as well as more robust analytical approaches. In the presented profiling effort, we integrated the latest advances in drug response measurement and focused on data diversity and quality rather than on breadth. We selected 32 breast cancer cell lines with a strong bias towards triple negative lines as well as 4 cell lines established from relevant patient-derived xenografts. We used high content microscopy to assay the phenotypic responses of the cell lines to a panel of 34 drugs made up largely of kinase inhibitors currently in the clinic along with some standard of care chemotherapeutics. The microscopy based drug response assay allowed us to measure drug potency, and to quantify the efficacy of the drugs in terms of growth inhibition and cell death. For the same cell lines, we used RNAseq to measure basal mRNA expression levels and shotgun mass spectrometry to measure endogenous protein levels.
The completeness and controlled conditions under which these data sets were collected provide confidence in their integration. The complementarity of these multi-omics data has allowed us to address questions about the landscape of, particularly triple negative, breast cancer cell lines. Such questions include: where do the patient-derived lines lay among the established cell lines? and how different are the landscapes defined by drug response phenotypes, mRNA expression, and protein levels? We used network-based algorithms to identify eigenstates of signaling pathways related to genomic events, and further explored these states in the TCGA data.
At the level of drug response, we have focused on important questions related to the clinical use of kinase inhibitors. In particular, we compared various CDK inhibitors in an effort to identify markers that are informative of response potency and efficacy. We have also looked at variability of the responses of the cell lines studied to multiple PI3K inhibitors that either target specific isoforms or all isoforms. Overall the data set that has been collected is a valuable resource for understanding drug response in triple negative breast cancer, and the transcriptomic and proteomic factors that influence it.
Citation Format: Mills CE, Hafner MA, Sorger PK. Integration of transcriptomic, proteomic and drug response data in triple negative breast cancer cell lines and PDX models [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 P4-08-02.
Abstract P4-09-01: Tumor suppressor control of the cancer stem cell angiogenic niche
Authors: Crowe D , Kramer K , Wu J 
Published: March 2017

Abstract
Mammary stem cells (MSC) expansion is associated with aggressive human breast cancer. The nuclear receptor peroxisome proliferator activated receptor γ (PPARγ) is a breast cancer tumor suppressor, but the mechanisms of this suppression are not completely characterized. To determine if PPARγ regulates MSC expansion in mammary cancer, we deleted PPARγ expression in the mammary epithelium of an in vivo model of basal breast cancer. Loss of PPARγ expression reduced tumor latency, and expanded the CD24+/CD49fhi MSC population. PPARγ null mammary tumors exhibited increased angiogenesis which was detected in human breast cancer. In vivo inhibition of a PPARγ regulated miR-15a/angiopoietin-1 pathway blocked increased angiogenesis and MSC expansion. PPARγ bound and activated a canonical response element in the miR-15a gene. PPARγ null tumors were sensitive to the targeted anti-angiogenic drug sunitinib but resistant to cytotoxic chemotherapy. Normalization of tumor vasculature with sunitinib resulted in objective response to cytotoxic chemotherapy. Chemotherapy treated PPARγ null mammary tumors exhibited luminal phenotype and expansion of unipotent CD61+ luminal progenitor cells. Transplantation of chemotherapy treated luminal progenitor cells recapitulated the luminal phenotype. These results have important implications for anti-angiogenic therapy in breast cancer patients.
Citation Format: Crowe D, Kramer K, Wu J. Tumor suppressor control of the cancer stem cell angiogenic niche [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 P4-09-01.