bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-03-04: The impact of Angelina Jolie (AJ)'s story on genetic referral and testing at an academic cancer centre
Authors: Raphael Jacques , Verma Sunil , Hewitt Paul , Eisen Andrea 
Published: May 2015

Abstract
Introduction/background
In May 2013, AJ revealed to the media that she had undergone preventive double mastectomy. The actress had a family history of breast and ovarian cancer and tested positive for the BRCA1 gene mutation. Media coverage has been extensive, but it’s not clear what messages the public and professional medical staff took from this personal story that sometimes could be misleading.
Methods
We conducted a retrospective review in our centre using data from the clinical database of the Familial Cancer Program in a tertiary care cancer centre. The impact of AJ’s story on genetic counseling referrals was assessed by comparing the number of referrals made 6 months before and after the story. In addition, the quality of referrals was reported by comparing the number of patients who qualified for genetic testing as defined by the Ontario Ministry of Health and Long Term Care and the ones who carried a BRCA1/2 mutation before and after the media release.
Results
The number of women referred for genetic counseling increased by 85% after the release of AJ’s story (479 before versus 887 after). This translated to an increase of 99% in the number of women who qualified for a genetic testing (211 before versus 419 after). Among them, 120 and 254 women had a history of breast and ovarian cancer in their family, 16 and 37 women had a history of male breast cancer in their family and 28 and 15 women were diagnosed with breast cancer at the age of 35 or less before and after AJ’s story respectively. Furthermore, the number of BRCA1/2 carriers identified increased by 107% (29 (14 BRCA1, 15 BRCA2) before and 60 (32 BRCA1, 28 BRCA2) after).
Conclusion
This study clearly shows that the number of genetic referrals doubled after AJ’s story. Nevertheless, the quality of referral remained the same with nearly the same percentage of patients who qualified for genetic testing and who were identified as BRCA1/2 carriers. The challenge is to meet the increased demand for cancer genetic services including screening, counseling, testing, and preventive surgery. After AJ’s story the current model of genetic counseling may need to be revisited.
Key words: Angelina Jolie; BRCA1/2; genetic referral; genetic counseling; genetic testing.
Citation Format: Jacques Raphael, Sunil Verma, Paul Hewitt, Andrea Eisen. The impact of Angelina Jolie (AJ)'s story on genetic referral and testing at an academic cancer centre [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 P1-03-04.
Abstract P1-06-06: Meta-analysis reveal novel mechanism of bisphenol A effect on mammary gland
Authors: Gu Xiang , Gao Hui , Wang Danhan , Bandyopadhyay Abhik , Dong Qiaoxiang , Sun LuZhe 
Published: May 2015

Abstract
Pubertal exposure to bisphenol A (BPA) has been shown to cause abnormal mammary gland development and neoplastic transformation in adults. However, the mechanism of this BPA effect still remains largely unknown. We exposed 21-day-old Balb/c mice to BPA by gavage (25 µg/kg/day) during puberty for 3 weeks. Primary mammary cells were isolated at 6 weeks, and 2 and 4 months of age and subsequently sorted into Lin-CD49f-CD24-stromal cells, Lin-CD49fhighCD24med MaSCs-enriched basal cells and Lin-CD49flowCD24high luminal progenitor-enriched cells with FACS for gene expression analysis. The Gene Ontology (GO) Enrichment Analysis shows that upon BPA treatment, the biological processes (BPs) significantly enriched in luminal compartment were related to response to organic substance and hormone stimuli at early stage (2 month old) whereas to cell cycle regulation at late stage (4 month old), consistent with published study in mammary gland morphology where BPA promoted the expansion of luminal population. However, the BPs enriched in spheres derived from basal cells (highly enriched with MaSCs) collected at late stage (4 month old) were mainly related to cell adhesion, epithelial differentiation and in stromal cells were related with vascular development for tissues collected either immediately after BPA treatment or 6 weeks later at 4-month of age. More interestingly, the Downstream Function Effects Analysis performed by Ingenuity Pathway Analysis reveal the changes in any compartments will all lead to significant activation of cancer-related downstream effects including hyperplasia, neoplasm of mammary tumor, proliferation of tumor cells and invasion of breast cancer, although there are few overlapping common genes in these compartments and conditions upon BPA treatment, indicating the different mechanism in response to BPA treatment and tumorigenesis. Network analysis revealed that the potential upstream regulators for these enriched BPs are TGFβ1, VEGF, PPARG, Estrogen/ Estrogen Receptor, glucocorticoid, ERK and NOTCH signaling. Together with our recently published data, this study reveals the difference in immediate and delayed response to pubertal BPA treatment and indicates that cross-talk between several growth factor and hormonal receptor signaling pathways may contribute to the altered cellular processes by BPA, consistent with the role of BPA as an endocrine disruptor.
Citation Format: Xiang Gu, Hui Gao, Danhan Wang, Abhik Bandyopadhyay, Qiaoxiang Dong, LuZhe Sun. Meta-analysis reveal novel mechanism of bisphenol A effect on mammary gland [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 P1-06-06.
Abstract P1-07-17: Transcription factor Fra-1 modulates the adhesive properties of breast cancer cells contributing to a metastatic phenotype
Authors: Oliveira-Ferrer Leticia , Kürschner Melanie , Labitzky Vera , Wicklein Daniel , Müller Volkmar , Schumacher Udo , Milde-Langosch Karin , Schröder Christine 
Published: May 2015

Abstract
Fra-1, a component of the transcription factor AP-1 family, has been found to be overexpressed in carcinomas with high metastatic potential such as in triple-negative breast cancer. The effect of Fra-1 on the morphology, motility and invasive potential of breast cancer cells has been previously described. Since tumor cell adhesion plays an essential role in the metastatic process, especially for extravasation from blood vessels, we investigated the influence of Fra-1 on breast cancer cell interactions with the endothelium.
Using the human breast cancer cell lines MCF7 (weakly invasive, estrogen receptor (ER)-positive) and MDA MB 231 (strongly invasive, ER-negative) with stable Fra-1 overexpression, we performed dynamic cell-flow adhesion assays on surfaces coated with E-selectin or with human pulmonary microvascular endothelial cells (HPMEC). Our analyses revealed increased adhesion of Fra-1 overexpressing MCF7 cells to E-selectin but also to activated endothelial cells, whereas the per se highly invasive and Fra-1-positive MDA MB 231 cell line showed enhanced cell rolling and tethering on E-selectin and endothelium-coated surfaces, but no increased firm adhesion after Fra-1 overexpression. These different behaviors correspond to an up-regulation of various adhesion-related proteins such as CD44, Integrin α5 and CEACAM6 in Fra-1 overexpressing MCF7 cells measured by microarray analysis and flow cytometry in comparison to weaker differences in the expression of adhesion molecules found in the Fra-1 overexpressing MDA MB 231 cell line. In line with these results and based on cDNA microarray data of breast cancer patients (n=175) high Fra-1 expression significantly correlates with shorter overall survival and higher rate of lung metastasis in ER-positive breast cancer patients (n=130), but has no impact on the prognosis of patients with ER-negative tumors.
Thus, in addition to its pro-invasive and pro-migratory effect, Fra-1 might influence the metastatic potential of breast cancer cells by changing the expression of adhesion molecules resulting in increased adherence to endothelial cells under flow conditions.
Citation Format: Leticia Oliveira-Ferrer, Melanie Kürschner, Vera Labitzky, Daniel Wicklein, Volkmar Müller, Udo Schumacher, Karin Milde-Langosch, Christine Schröder. Transcription factor Fra-1 modulates the adhesive properties of breast cancer cells contributing to a metastatic phenotype [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 P1-07-17.
Abstract P1-07-35: Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer
Authors: Powell Catherine A , Nasser Mohd W , Wochna Jacob C , Shilo Konstantin , Zhang Xiaoli , Ganju Ramesh K 
Published: May 2015

Abstract
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has a poor prognosis for patients, not only due to its aggressive nature, but also due to the lack of effective therapeutic strategies. High mortality is associated with metastasis of the primary TNBC. We analyzed the role of fatty acid binding protein 5 (FABP5), an intracellular fatty acid transport protein, in aggressive breast cancers, especially TNBC. FABP5 expression was analyzed in a tumor microarray (TMA) containing 423 breast cancer patient samples and found that FABP5 expression is associated with tumor grade, triple negative status, and disease-free survival. Next, a mechanistic approach was taken and found that FABP5 knockdown TNBC cell lines express lesser EGFR protein compared to control, and upon EGFR activation express less phospho-FAK and phospho-Pyk2. We found that EGFR was not down regulated at the transcriptional level in FABP5 knockout cells. Further analysis indicated the role for Cbl, an E3 ubiquitin-protein ligase, as a potential mechanistic target for the down-regulation of EGFR protein in FABP5 knockdown cell lines. EGFR is over-expressed in aggressive breast cancers, especially TNBC. Though EGFR is highly expressed in aggressive subtypes of breast cancer, targeted therapeutic strategies have not been successful in clinic. EGFR has been shown to be involved in distant metastasis in aggressive breast cancers. We found a correlation between FABP5 and EGFR expression and metastasis-free survival using publically available datasets from The Cancer Genome Atlas. We next studied the functional consequence of FABP5 knockdown in TNBC cell lines. We showed that EGF-induced FABP5 knockdown cells migrated less compared to control. Additionally, FABP5 knockdown cells were significantly less able to migrate into a wound in response to EGF stimulation. EGF-induced cell attachment of FABP5 knockdown cells is significantly decreased compared to control. Our findings suggest FABP5 modulates metastatic potential of TNBC through alterations in EGFR expression and downstream migratory signaling molecules.
Citation Format: Catherine A Powell, Mohd W Nasser, Jacob C Wochna, Konstantin Shilo, Xiaoli Zhang, Ramesh K Ganju. Fatty acid binding protein 5 promotes metastatic potential of 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 P1-07-35.
Abstract P1-12-16: Efficacy of adjuvant tamoxifen in hormone receptor-positive premenopausal breast cancer patients according to the body mass index
Authors: Altundag Kadri , Sendur Mehmet AN , Aksoy Sercan , Babacan Taner , Ozisik Yavuz 
Published: May 2015

Abstract
Introduction: Obesity is an independent risk factor for the development of breast cancer and has been associated with poor breast cancer outcomes. But, this association usually depend on hormone-receptor positivity and ovarian activity. Obesity was confirmed as an adverse prognostic factor in patients treated with aromatase inhibitors, but the adverse effects in patients treated with tamoxifen was not known exactly. Thus, we aimed to examine the efficacy of adjuvant tamoxifen in hormone receptor-positive premenopausal breast cancer patients according to the body mass index (BMI).
Material-Methods: Newly diagnosed hormone receptor-positive breast cancer patients who were premenopausal and non-metastatic were enrolled to the study. Patients with BMI ranging between 18.5 and 24.9 kg/m2 as normal weight patients (Arm A, n = 408), and patients with a BMI ranging ≥ 25 kg/m2 were overweight and obese patients (Arm B, n = 418).
Results: The median follow-up time for this analysis was 36 (6-327) months. The median age was 39.5 (22-57) and 43 (20-56) in Arm A and Arm B, respectively (P&lt;0.0001). The mean BMI was 22.1 ± 1.8 kg/m2 and 29.2 ± 3.3 kg/m2 of Arm A and Arm B, respectively ( P = &lt;0.001). In both normal weight and overweight patients, the other baseline clinico-pathologic properties and the treatment history with radiotherapy and chemotherapy were similar and not statistically significant. In overweight and obese patients the history of diabetes mellitus and hypertension was significantly higher compared to normal weight patients. In patients with normal weight patients DFS rate was 88.5% and 78.2% whereas in overweight and obese patients DFS rate was 87.2% and 70.9% in the third and fifth years respectively (Figure 1) ( P = 0.43). In patients with normal weight patients OS rate was 98.5% and 93.2% whereas in overweight and obese patients OS rate was 94.6% and 87.4% in the third and fifth years respectively (Figure 2) ( P = 0.02).
Conclusion: Our study showed that BMI have no worse effect on recurrence risk in patients treated with tamoxifen in hormone-receptor positive premenopausal breast cancer. Poor survival outcome was observed in overweight and obese patients can be due to dose limitations of chemotherapeutic agents and higher rate of comorbid diseases.
Citation Format: Kadri Altundag, Mehmet AN Sendur, Sercan Aksoy, Taner Babacan, Yavuz Ozisik. Efficacy of adjuvant tamoxifen in hormone receptor-positive premenopausal breast cancer patients according to the body mass index [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 P1-12-16.
Abstract P1-15-13: Short term toxicity of intra-operative radiotherapy for patients with breast cancer treated at a single center
Authors: Shai Ayelet , Zur Maoz , Leviov Michelle , Bitterman Arie , Eitan Shiloni , Steiner Mariana 
Published: May 2015

Abstract
Introduction:
Intra-operative radiotherapy (IORT) is increasingly being used for the treatment of low risk breast cancer. In the randomized TARGIT trial, late toxicity was not different between patients treated with IORT and external beam radiotherapy. Early toxicity of IORT has not been fully characterized.
Methods:
IORT with one dose of 20 Gy using the Intrabeam© device has been offered as an alternative to standard treatment as part of a single center prospective single arm trial. Patients over 60 years with clinically node negative, &lt; 2 cm invasive duct carcinomas were eligible. Patients aged 50-60 years, patients with tumors 2-3.5 cm and patients with invasive lobular carcinomas were treated with IORT if they were not candidates for standard treatment.
For the present study information regarding complications occurring within the first year after surgery was analyzed. Patients treated between 2006 and 2012 were included in this analysis.
Results:
393 patients were treated from 2006 – 2012. 4 were lost to follow up. Median age was 70 years (55-90) and median clinical tumor size was 1.2 cm (5-30).
102 patients (26.2%) had a complication. Infections were most frequent. Misdiagnosis of radiation dermatitis as infection in some cases cannot be excluded. Clinically meaningful seromas occurred in 10.2% of patient and 8.2% had a wound dehiscence, possibly related to rupture of pre-existing seromas.
Table 1Complication typeN (%)N with grade 3 (%)N with grade 4 (%)median time to recovery (range)Infection42 (11)3 (3.3) 0.62 (0.1 - 3.8)Seroma40 (10.2) 13.2 (0.3-50)Wound dehiscence33 (8.5)2 (0.5) 5.8 (0.36-15.3)Bleeding11 (2.8)3 (0.8) Skin necrosis2 (0.5) 2 (0.5)3.88 (3.45-4)frequency, severity and time to recovery of acute complications of IORT.
18 patients (4.6%) had a grade 3 complication. 2 patients (0.5%) had grade 4 radiation induced skin necrosis of small size and both resolved within 4 months. All other complications resolved completely (table 1). Risk factors for complications in this cohort will also be presented.
Conclusions:
Intra-operative radiotherapy was associated with a relatively high rate of clinically meaningful seromas and wound dehiscence and rare small size skin necrosis. Most complications were mild – moderate. 5% of patients experienced grade 3 or 4 complications, and all resolved completely. Further study of the factors predisposing to severe complications is warranted.
Citation Format: Ayelet Shai, Maoz Zur, Michelle Leviov, Arie Bitterman, Shiloni Eitan, Mariana Steiner. Short term toxicity of intra-operative radiotherapy for patients with breast cancer treated at a single center [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 P1-15-13.
Abstract P2-01-09: Application of the Z0011 criteria on Dutch breast cancer patients
Authors: Verheuvel Nicole C , Tjan-Heijnen Vivianne CG , Voogd Adri C , Roumen Rudi MH 
Published: May 2015

Abstract
Background
The American College of Surgeons Oncology Group reported a randomized controlled trial (Z0011-trial) among women with T1-2N0M0 breast cancer treated with breast conserving therapy. It showed that axillary lymph node dissection may be redundant in selected sentinel node positive patients. Though, it raises questions as to the general applicability of these results. Therefore, this study aims to examine the practice changing effect and the clinical relevance of the criteria described in the Z0011 trial, when applied to a Dutch population of patients diagnosed with invasive breast cancer.
Methods
This is a multicenter study including patients with T1-2N0-1M0 invasive breast cancer treated in either of the 10 different hospitals affiliated with the Dutch National Cancer Registry region South in the period between January 2007 and December 2012. All patients underwent a clinical examination, a mammography and sonographic examination of the breast and the ipsilateral axilla. Chi-square analyses or a Fisher’s exact test were used to assess differences in patient and tumor characteristics the Z0011 population and the Dutch cohort. A p-value of ≤0.05 was considered statistically significant.
Results
A total of 11,031 patients had invasive breast cancer, of whom 5368 patients were treated with breast conserving therapy. In 6.8% axillary status was determined by the ultrasound guided lymph node biopsy and in 93.1% axillary metastases were found trough the sentinel node procedure after a negative or inconclusive ultrasound. When applying the Z0011 criteria to our study population of node positive patients, 5.7% of all breast cancer patients, equalling 11.8% of patients receiving breast conserving therapy, met the Z0011 criteria.
Conclusion
These results suggest that when applying the Z0011 criteria to all node positive patients, including patients with a positive sentinel node and patients with a positive ultrasound guided lymph node biopsy, only in 5.7% of all invasive breast cancer patients could be spared an ALND and its morbidity. This is a small practice changing effect. Nevertheless, it is worthwhile to consider implementing the findings of Z0011 trial in daily clinical practice.
Citation Format: Nicole C Verheuvel, Vivianne CG Tjan-Heijnen, Adri C Voogd, Rudi MH Roumen. Application of the Z0011 criteria on Dutch breast cancer patients [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 P2-01-09.
Abstract P2-01-14: Pre-operative axillary staging results in over-treatment in some breast cancer patients
Authors: Pieri Andrew , Cain Henry , Aspinall Sebastian 
Published: May 2015

Abstract
Introduction
Following a diagnosis of breast cancer, pre-operative ultrasound staging of the axilla is recommended. Patients found to have metastatic disease on biopsy or FNA can proceed directly to axillary clearance (ALNC) at the time of their breast tumour excision. However, although ultrasound staging is a sensitive test to detect axillary disease, it does not differentiate between low and high volume nodal metastasis. Recent evidence suggests that, in selected patients with low volume axillary disease following SLNB, completion ALNC may be safely omitted. This has been reflected in the recently updated ASCO guidelines. In light of this current trend towards axillary conservation, some patients undergoing ALNC after positive axillary staging may be over-treated.
The aims of this study is to establish the nodal burden of patients undergoing ALNC following positive axillary staging and to compare the nodal burden of those patients with those undergoing completion ALNC after a positive SLNB.
Methods
Data was collected prospectively over 12 months from nine hospitals within the North of England Cancer Network. Age, tumour characteristics, breast operation, axillary staging results, axillary operation(s) and nodal results were recorded.
Results
A total of 1010 patients with breast cancer underwent pre-operative axillary staging. 215 patients (21%) had an ALNC. Of these, 115 (53%) cases underwent a primary ALNC after positive staging. The remaining 100 (47%) patients had a completion ALNC following a positive SLNB. The nodal burden for patients undergoing ALNC is shown in the table below:
Total number of positive nodesALNC after positive stagingALNC after positive SLNB n patients% patientsn patients% patients087001322847472131124243121011114111044≥539341414Totals115 100
Analysis of the data revealed that tumour size was a significant predictor of low volume axillary disease (i.e. &lt;3 nodes positive) [p=0.02, Mann-Whitney test].
Conclusion
In this study, 46% of patients undergoing ALNC after positive staging had low volume disease (2 or less positive nodes). In the context of recent evidence if these patients had undergone a SLNB following the positive pre-operative staging they may have avoided a completion ALNC.
This study demonstrates tumour size to be a significant predictor of low volume axillary disease and thus may be an important factor to consider alongside pre-operative staging when selecting patients who may be better managed by a SLNB rather than proceeding directly to ALNC.
Citation Format: Andrew Pieri, Henry Cain, Sebastian Aspinall. Pre-operative axillary staging results in over-treatment in some breast cancer patients [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 P2-01-14.