bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-08-31: Putative role of genetic variants of eNOS in survival and toxicity of patients given antiangiogenic therapy
Authors: Del Re M , Fontana A , Del Re I , Bona E , Salvadori B , Ferrarini I , Landucci E , Fancelli S , Bertolini I , Michelotti A , Falcone A , Danesi R 
Published: August 2014

Abstract
Background: The development of tumor angiogensis is mainly driven by vascular endothelial growth factor (VEGF), which is strongly overexpressed in many cancers. VEGF induces the expression of the endothelial nitric oxide (NO) synthase (eNOS) and the resultant overproduction of NO may be associated with recruitment of inflammatory cells, disruption of endothelial barrier, edema and impaired drug delivery within tumors (1). Functional polymorphisms in the eNOS gene, including -786C&gt;T and 894G&gt;T, have been associated with impaired production of NO and higher incidence of hypertension (HT) (2), diabetic nephropathy (3) and glaucoma (4). Since suppression of VEGF-eNOS signal transduction by antiangiogenic drugs may normalize tumor vasculature by restoring interstitial fluid pressure and drug distribution in tumors, but may induce HT in patients, the purpose of this study was to examine the association between the major eNOS variants -786C&gt;T and 894G&gt;T with treatment outcome and risk of HT in metastatic breast cancer (MBC) patients given bevacizumab. Methods: Sixty-five MBC patients given bevacizumab as per approved indication were enrolled. Main characteristics were: mean age 49.5 years (range 29-73) at first diagnosis, 53 years (range 34-74) at metastatic progression and PS 0-1. Four subjects with HT and 1 patient with compensated cardiovascular disease were also included. First-line chemotherapy for metastatic disease was taxol plus bevacizumab. Germline DNA was extracted from peripheral blood with the Qiamp Mini Kit (Qiagen, Milano, Italy) and examined for eNOS -786C&gt;T and 894G&gt;T variants by Real Time PCR (Life Sciences 7900HT platform) and automatic sequencing (Life Sciences 3100 Avant). The study was approved by the local Ethics Committee. Results: Genotype frequencies are reported below (Table 1). The presence of -786TT genotype was associated with longer PFS compared with the other genotypes (median PFS 95%CI, CC/CT = 9 vs TT = 12 months, Log-rank [Mantel Cox] test p = 0.0066), but not with any grade of HT. Also the 894GT/TT was associated with longer PFS compaed with the GG homozygous wild-type genotype (median PFS 95%CI, GG = 7,5 vs GT/TT = 10 months, Log-rank [Mantel-Cox] test p = 0,0497). The incidence and severity of HT did not vary among genotypes. Conclusion: Patients bearing deficient eNOS variant did not experience higher risk or severity of HT with respect to the wild-type allele but enjoied a longer PFS.
Table 1. Genotype frequenciesSNPFrequencies%Frequencies%Frequencies%-786C&gt;TCCCTTT 37%33.8%26.2%894G&gt;TGGGTTT 41.5%53.8%4.6%
References
1. Goel S et al. Physiol Rev 2011;91:1071
2. Niu W, Qi Y. PLoS One 2011;6:e24266
3. Rahimi Z et al. Dis Markers 2013;34:437
4. Awadalla MS et al. Invest Ophtalmol Vis Sci 2013;54:2108.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-31.
Abstract P1-08-35: Androgen receptor expression and changes in serum dehydroepiandrosterone sulfate levels in locally advanced breast cancer patients who received neoadjuvant chemotherapy
Authors: Park S , Lee JS , Park JM , Park HS , Kim SI , Park B-W 
Published: August 2014

Abstract
Purpose: The associations between androgen receptor (AR) expression, serum dehydroepiandrosterone-sulfate (DHEA-S) level and response to neoadjuvant chemotherapy (NCT) were investigated in locally advanced breast cancer patients who received NCT.
Methods: Between May 2008 and April 2013, a total of 346 patients underwent NCT mainly based on anthracycline with or without taxane regimens. Biomarkers including AR were immunohistochemically determined using biopsy specimens before NCT and tumors with ≥ 1% nuclear staining were considered positive for AR. Changes in serum DHEA-S levels before and after NCT were examined by chemiluminescent immunoassay (Access DHEA-S, Beckman Coulter, Inc., Brea, CA) in 205 (59.2%) patients. Pathologic complete response (pCR) was defined as the absence of residual invasive carcinomas in the surgical specimens of breast and lymph nodes. Breast cancer subtypes were categorized by immunohistochemistry of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67.
Results: Mean age at diagnosis was 49.7 years (range, 26–76). Clinical tumor size was ≥ 2cm in 243 (70.2%) patients and 318 (91.9%) showed node-positive disease at initial presentation. AR-positive tumor was determined in 195 (56.4%) patients and 95 (27.5%) achieved pCR after NCT. AR-negative tumors were significantly associated with grade III, ER-negative, PR-negative, HER2-negative, high Ki-67 index, and triple-negative subtype tumors. By univariate logistic regression analysis, AR-negative tumor showed significantly higher odds ratio of 1.650 (95% CI, 1.026–2.654; p-value, 0.039) for achievement of pCR. Nevertheless, not AR status but breast cancer subtype, longer duration of NCT and use of targeted agents remained to be significant for pCR by multivariate model. In the analysis of subgroup by breast cancer subtypes, AR-negative tumor was associated with pCR in 75 patients with the low proliferative luminal A subtype, while AR-positive tumor achieved higher pCR in 59 patients with the HER2-positive luminal B subtype. In 205 patients available for serum DHEA-S levels, there was no difference in DHEA-S between pCR and non-pCR groups, although a trend of decrease in DHEA-S after NCT was noted among postmenopausal AR-positive or luminal A subtype women who achieved pCR.
Conclusions: AR expression might predict pCR in locally advanced breast cancer patients who undergo NCT, but this implication could be different according to breast cancer subtypes. Clinical significance of changes in serum DHEA-S levels during NCT remains to be elucidated.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-35.
Abstract P1-08-36: Neoadjuvant trial of bevacizumab (B) and trastuzumab (T) in combination with weekly paclitaxel (P) as neoadjuvant treatment in HER2-positive breast cancer: A phase II trial (AVANTHER). Analysis of biomarkers
Authors: Fernández M , Martinez N , Calvo I , Garcia E , Ugidos L , Herrero M , Quijano Y , Durán H , Garcia M , Suarez A , López-Rios F , Perez D , Perea S , Hidalgo M , Garcia-Estevez L 
Published: August 2014

Abstract
Background: AVANTHER is a phase II trial of preoperative systemic therapy combining B with T and P in a weekly regimen in HER2 positive breast cancer to assess safety and efficacy of the combination. The primary endpoint was pathological complete response (pCR), defined as the absence of invasive disease at the time of histological study. Tissue samples were collected at baseline and the relationship between the expression of PTEN, PI3KCA, TOPO 2a, VEGF, activation of insulin growth factor 1-receptor (IGF1R) and pCR was assessed.
Methods: Patients (pts) with centrally-confirmed HER2–positive (IHC 3+ or FISH amplified) breast cancer (stage II or III including locally advanced) received neoadjuvant chemotherapy (NC) with weekly P (80mg/m2/week) for 12 weeks in combination with weekly T (4mg/kg loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for 4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin plus cyclophosphamide every 3 weeks (4 cycles). Tumor samples were evaluated for the expression of PTEN and TOPO 2α by fluorescent in situ hybridization (FISH), IGF-1R, VEGF, and EGFR using standard immunohistochemistry (IHC). Status of PI3KCA was determined using Fluidigm-based real-time PCR.
Results: A total of 44 pts were enrolled. Median tumor size: 3.9 cm. Nine (21%) pts had stage IIA; 19 (45%) stage IIB; 10 (24%) stage IIIA and 4 (10%) stage IIIB. Twenty-nine (69%) pts had estrogen positive receptors. PCR achieved was 42.9%. PTEN expression was normal in all pCR group and 1 patient (pt) (3.8%) had a PTEN deletion in group with no pCR. PI3KCA was mutated in 3pts (16.7%) (1pt E542k and 2 pts H1047r) in the pCR group and 4 pts (15.4%) (1pt E545k, 1pt G1049r and 2 pts H1047r) in the no pCR. Topo 2α was amplified in 8 pts in both groups. The expression of IGFR 1 was negative in 44.4% in the pCR group and 15.4% in patients with no pCR (p = 0.04). VEGF was positive in 7pts (39%) in pCR group and 10pts (38.5%) in no pCR.
Conclusions: Our results are in agreement with some prior studies that show that expression of IGFR could be correlated with trastuzumab resistance. Therefore, these findings raise a hypothesis to be validated in prospective studies.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-36.
Abstract P1-08-38: HER2 heterogeneity affects trastuzumab responses and survival in patients with HER2-postive metastatic breast cancer
Authors: Lee HJ , Seo AN , Kim EJ , Jang MH , Suh KJ , Ryu HS , Kim YJ , Kim JH , Im S-A , Gong G , Park IA , Jung KH , Park SY 
Published: August 2014

Abstract
Purpose: Heterogeneity of HER2 gene amplification is found in a subset of breast cancers. However, it is not known whether breast cancers with heterogeneous HER2 amplification respond differently to HER2-targeted therapy than those with homogeneous amplification. In this study, we investigated the relationship between HER2 heterogeneity and trastuzumab resistance and clinical outcomes in patients with HER2-positive metastatic breast cancer.
Patients and methods: We studied tumor tissues from 127 patients with HER2-positive metastatic breast cancers who had received trastuzumab-based chemotherapy. Regional and genetic heterogeneity of HER2 amplification was determined in three different areas of each tumor by immunohistochemistry (IHC) and silver in situ hybridization. We also assessed the overall levels of HER2 amplification, and the proportion of tumor cells with a HER2/CEP17 ratio &gt;2.2 or HER2 overexpression (IHC score of 3+). HER2status including HER2 heterogeneity was correlated with trastuzumab responses and survival of the patients.
Results: HER2regional and genetic heterogeneity was confirmed in 7.8% and 3.6% of cases, respectively. Poor response to trastuzumab was associated with overall low-level amplification, HER2regional heterogeneity, HER2/CEP17 ratio &gt;2.2 in &lt;80% of tumor cells, and HER2 IHC score of 3+ in &lt;75% of tumor cells. In survival analyses, low-level HER2 amplification, HER2regional heterogeneity, and HER2/CEP17 ratio &gt;2.2 in &lt;80% of tumor cells were associated with shorter time to progression and lower overall survival in univariate and multivariate analyses.
Conclusion: Accurate assessment of HER2 status including HER2 heterogeneity is important in predicting trastuzumab responses and outcomes in patients with HER2-positive metastatic breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-38.
Abstract P1-09-06: Breast cancer in the Pan-American region: Inequities in incidence and mortality rates according to the human development index
Authors: Barrios CH , Werutsky G , Martínez-Mesa J 
Published: August 2014

Abstract
Background: Breast cancer (BC) is considered a public health problem in countries of the Pan-American Health Organization (PAHO). Data from GLOBOCAN 2008 shows BC age-adjusted incidence and mortality rates of 57.1 and 13.7 per 100,000 inhabitants in the region. The aim of the present study is to evaluate the association between BC incidence and mortality rates with the human development index (HDI) in PAHO countries.
Methods: This is an ecological analysis including 29 countries (PAHO) with reported data both in GLOBOCAN 2008 and in the 2013 United Nation Development Reports (UNDP). In alphabetical order the participant countries were Argentina, Bahamas, Barbados, Belize, Bolivia, Brazil, Canada, Chile, Colombia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala, Guyana, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Trinidad and Tobago, United States of America, Uruguay and Venezuela. HDI is a composite statistic of life expectancy, education, and income and was analyzed as a continuous score. Age-adjusted BC incidence and mortality rates were taken from GLOBOCAN 2008 and log-transformed due to skewness. Pearson correlation and simple linear regression were performed using Stata 12 (Stata Corp., College Station, USA).
Results: A positive correlation was found between HDI and log-transformed age-adjusted BC incidence and mortality rates. The correlation coefficient between HDI and BC incidence rate was 0.68 (p-value&lt;0.001). The correlation with BC mortality rate was 0.49 (p-value = 0.007). Linear regression showed that an increase in one HDI unit lead to a gain of 3.51 points (se = 0.72; p-value&lt;0.001) in the incidence rate and 2.14 points (se = 0.73; p&lt;0.007) in the mortality rate.
Conclusion: HDI inequities are important and should be considered in the analysis of the difference in BC incidence and mortality rates seen in PAHO countries.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-09-06.
Abstract P1-09-10: Disparities in presentation of breast cancer in a geriatric population
Authors: Ursem C , Camacho F , Anderson R , Kimmick G 
Published: August 2014

Abstract
Background: Although there are known to be disparities by socioeconomic status (SES) in breast cancer presentation, this has not been as well studied in the elderly. We examined older women in North Carolina (NC) using insurance status as an indicator of SES. Dual Medicaid/Medicare (dMM) status was used as a surrogate for low SES and Medicare only (M) as a surrogate for higher SES.
Methods: From the 1999-2002 NC Central Cancer Registry, we identified women age ≥65 years presenting with nonmetastatic breast cancer, having surgery within 60 days of diagnosis, no neoadjuvant therapy, and insured by Medicare only or dual Medicaid/Medicare. We used Chi-square tests to compare demographic and tumor characteristics, including: age, race, ACE comorbidity index, tumor size, lymph node status (LN), ER/PR status and HER2 status.
Results: We identified n = 3088 women with mean age 75 (SD 6.69) years, including 560 dMM and 2528 M insured women. We found that the dMM patients were older than M patients, with 57.7% ≥75 years, vs. 42.6% (p&lt;0.001) and mean age 76.9 vs. 74.5 years (p&lt;0.001), as well as composed of more African Americans, 34.6% vs. 6.6% (p&lt;0.001). The dMM group also had significantly more comorbidity, with ACE comorbidity index: none 21.4% vs. 40.0%, minimal 45.2% vs. 43.2%, moderate 15.5% vs. 9.8% and severe 17.9% vs. 6.9% (p&lt;0.001). The dMM patients were diagnosed more often with regional as compared to local disease, 26.3% vs. 19.7% (p&lt;0.001) and had larger tumors at diagnosis, mean 23.46mm vs. 18.50mm (p&lt;0.001). Additionally, the dMM patients were found to have more LN involvement: 0 LN in 73.4% vs. 80.0%, 1-3 LN in 19.6% vs. 15.5%, 4-9 LN in 5.7% vs. 3.5% and ≥ 10 LN in 1.3% vs. 1.1% (p = 0.004). We did not find significant differences in tumor histology, grade, ER/PR subtype or HER2 status.
Conclusions: We found that in a population of elderly breast cancer patients, lower SES as defined by Medicaid insurance status was associated with older age, African American race and more advanced comorbidity. These same patients presented with move advanced disease, characterized by larger tumors and more LN involvement.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-09-10.
Abstract P1-09-18: Doctors with breast cancer are more likely to opt for mastectomy: Fact or fiction?
Authors: O'Connell RL , Gui G , Rusby JE 
Published: August 2014

Abstract
Introduction
Doctors who are diagnosed with breast cancer make up a small but unique subset of women owing to their medical knowledge. Anecdote suggests that doctors with breast cancer are more likely to opt for mastectomy than non-medically qualified patients.
The primary aim of this study was to compare mastectomy rates in medically-qualified doctors with degree-educated controls with breast cancer.
Methods
Research ethics approval was obtained. Patients diagnosed with breast cancer between 1/1/2006 and 31/12/2011 and who had signed a generic research consent form were included in this observational study. Every patient was screened by occupation independently by 2 investigators to identify medically-qualified doctors and suitable (degree-educated) controls such as teachers, lawyers etc. Those with a medical background (e.g.nurse, physiotherapist etc) but not a medical doctor were excluded. Further exclusions were necessary if patients who were reviewed for a second opinion, reconstruction only or radiotherapy only or were male, surgery was not performed, BRCA positivity (might opt for bilateral mastectomy), unusual histology (e.g. lymphoma, sarcoma), recurrence or had a past history of contralateral breast cancer. Doctors and controls were compared by age, tumour characteristics and treatments using Student's t test for continuous variables and Fisher's exact test for categorical variables.
Results:
In total 8623 patients were reviewed and/or treated for breast cancer of whom 5215 had signed the generic research consent form. Overall 607 were either doctors or appropriate occupation controls. After exclusions 473 patients were eligible to be included in the analysis. Of these: 51 were medically-qualified doctors and 422 were degree-educated (controls).
Comparison of tumour characteristics and treatment between doctors and controls DoctorsControlspNumber51422 Mean age (years)53.350.80.11Mean total tumour size (mm)32.231.60.89 Number (%)Number (%)pDCIS alone10(20)53 (13)0.18Node positive16 (31)157 (37)0.44ER positive45 (88)337 (80)0.18HER2 positive12 (24)113 (27)0.73 Neoadjuvant chemotherapy6 (12)58 (14)0.83Adjuvant chemotherapy14 (27)154 (36)0.21 mastectomy17 (33)145 (34)1.00Immediate reconstruction9 (53)65 (45)0.61Post mastectomy radiotherapy5 (29)68 (47)0.20Comparison of age, tumour characteristics, mastectomy, chemotherapy and post mastectomy radiotherapy rates between doctors and the control group
There was no statistical difference in age and tumour characteristics between the doctors with breast cancer and the control group. There was no statistical difference in chemotherapy rate, mastectomy rate, or uptake of immediate breast reconstruction or post-mastectomy radiotherapy in mastectomy patients between the doctors with breast cancer and the control group.
Conclusion
Doctors in this study were not statistically more likely to undergo mastectomy than controls.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-09-18.
Abstract P1-10-01: Patient advocate involvement shapes UK’s first national breast cancer tissue bank - The breast cancer campaign tissue bank
Authors: Morgan A , Gath J , MacKenzie M , Matthews A , Stobart H , Turner L , Wilcox M 
Published: August 2014

Abstract
The Breast Cancer Campaign Tissue Bank (BCCTB) was initiated in 2010 after the charity Breast Cancer Campaign heard from breast cancer experts that insufficient high quality breast cancer tissue was preventing research which would impact people with breast cancer1. The charity decided to involve patient advocates in the development of the BCCTB from the beginning.
Two advocates reviewed the initial applications to form the BCCTB. These included both single and multi-centre applications so they suggested that, rather than choosing one centre to form the Bank, the charity consider a collaboration of centres. Throughout the development of the BCCTB, the patient advocates asked the ‘elephant in the room’ questions and brought a different perspective. They also helped to design the Bank's processes, including the consent process and asking that all tissue applicants produce a lay summary of their research.
There are now two advocates on the Board which provides strategic direction to the BCCTB. The advocates have equal status to other Board members. There are also three advocates on the Tissue Access Committee which controls the use of tissue in the Bank. Lay summaries of projects have to be approved by all advocates before an application can proceed. This means that no precious tissue is released without the approval of a lay person, who can ensure maximum patient benefit will be achieved from any research. The Bank's data return policy was also driven by the patient advocates who were keen that the tissues donated were used to their maximum benefit. This has resulted in the first publication from BCCTB2
Patient advocates have been involved in promoting the use of tissue from the bank presenting at conferences and at BCCTB road shows. Patient advocates have also been involved in asking potential donors to consent to donate to the tissue bank.
The involvement of patient advocates in the development and oversight of the BCCTB has shown researchers that patient and public involvement works. The advocates can also help promote the Bank and the benefits of tissue donation to both professionals and lay groups.
The patient advocates involved in the Breast Cancer Campaign Tissue Bank are members of the charity Independent Cancer Patients’ Voice
1. Thompson P, Brennan K, Cox A, Gee J, Harcourt D, Harris A, Harvie M, Holen I, Howell A, Nicholson R, Steel M, Streuli C. Evaluation of the current knowledge limitations in breast cancer research: a gap analysis. Breast Cancer Res 2008: 10(2); R26.
2. Speirs V, Morgan A. Investment biobanking – increased returns on tissue samples. Nat Rev Clin Onc 2013; 10:128-129.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-10-01.