bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative proteomic analysis of radioresistant breast cancer cell lines.
Authors: Smith L , Potts D , Qutob O , Watson MB , Beavis AW , Garimella V , Lind MJ , Drew PJ , Cawkwell L 
Published: December 2010

Abstract
Abstract #5074
Background: Resistance to radiotherapy may be a significant factor in the development of local recurrence following surgical resection and radiotherapy. We aimed to develop a novel in vitro model of radioresistance using a breast cancer cell line and to subsequently identify molecular biomarkers which may be associated with the radioresistant phenotype. We utilised a quantitative proteomics technique (iTRAQ) based on MALDI-TOF/TOF mass spectrometry (MS) to identify differentially expressed proteins.&#x2028; Material and Methods: We established 3 novel breast cancer cell sublines which were significantly resistant to radiotherapy when compared with the parental cells. The radioresistant sublines were created by irradiating cells in fractionated doses of 2Gy up to a total dose of 40Gy. Sufficient time was allowed for the cells to recover between subsequent irradiations. A dose response curve was assessed at the end of treatment to demonstrate a statistically significant increase in radioresistance for each novel cell subline when compared with parental cells. One radioresistant/parental cell pair was first analysed using in-solution digestion and liquid chromatographic separation with protein identification by MALDI-TOF/TOF (LC-MALDI analysis) on an Applied Biosystems 4800 Plus instrument. Quantitative iTRAQ (Applied Biosystems) was then performed on the same instrument for all 3 radioresistant/parental cell pairs.&#x2028; Results: A total of 586 and 652 proteins were identified in T47D and T47DRR cells respectively by LC-MALDI. Those proteins identified in both cell lines and any redundant entries were removed to reveal those proteins which were unique to each cell line. In total 244 unique proteins were identified in T47D cells and 311 unique proteins were identified in T47DRR cells.&#x2028; Comparison of the 3 pairs of radioresistant/parental cell samples by iTRAQ revealed a number of differentially expressed proteins. Using a standard ≥2-fold change in expression, these iTRAQ analyses revealed significant changes in the expression of 51 proteins in one or more of the radio-resistant derivatives.&#x2028; Further confirmation by immunoblotting is underway. Currently the decrease in expression of 26S proteasome associated subunits has been confirmed by this method.&#x2028; Conclusion: LC-MALDI and iTRAQ analysis has revealed a large number of candidate proteins which may be associated with a radioresistant phenotype. These now require further confirmatory studies. These MS-based techniques offer a powerful proteomic approach to identify candidate biomarkers which may be involved in radioresistance.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5074.
Enterolactone but not genistein decreases estradiol-induced tumor growth, angiogenesis, and secreted VEGF in vivo in human breast cancer.
Authors: Saarinen NM , Abrahamsson A , Dabrosin C 
Published: December 2010

Abstract
Abstract #5081
Phytoestrogens have been shown to be potential compounds in breast cancer prevention and treatment by poorly understood mechanisms. There are two major classes of phytoestrogens in the diet; lignans and isoflavones. One main phytoestrogen in Western diet is the mammalian lignan enterolactone (ENL) whereas soy is the major source of the isoflavone genistein (GEN) usually found in Eastern diets. In this paper we investigated the effects of ENL and GEN on estradiol induced breast cancer growth in nude mice. Ovariectomized mice treated with a continuous release of estradiol were used. MCF-7 tumors were established and mice were fed with basal diet (BD), or BD with added ENL, GEN, or a combination of ENL and GEN. Tumor growth was followed and microdialysis was used to sample extracellular VEGF and FGF-2 in vivo after 2-3 weeks of treatment. We show that ENL alone or in combination with GEN, counteracted estradiol-induced growth and angiogenesis of solid tumors. GEN alone did not affect tumor growth or angiogenesis compared with BD. The pro-angiogenic extracellular levels of VEGF in vivo were significantly decreased by ENL and ENL+GEN diets compared with tumors in the BD group whereas GEN diet alone did not affect the levels compared with BD. FGF-2 levels were similar in all groups. Our in vivo findings were confirmed in vitro. By adding ENL and/or GEN, estradiol-induced VEGF secretion in MCF-7 cells decreased significantly in the ENL and ENL+GEN groups whereas GEN alone had no effects compared with estradiol exposed cells. FGF-2 was unaffected by estrogen and phytoestrogen exposure compared with control cells without added hormones. Estradiol up-regulated VEGFR-2 in human umbilical vein endothelial cells and this up-regulation was inhibited by ENL suggesting a pro-angiogenic effect by estradiol by two different mechanisms, both of which were inhibited by the addition of ENL. Our results suggest that ENL has potent anti-estrogenic effects on ER+ breast cancer whereas GEN failed to inhibit estradiol-induced tumor growth and VEGF secretion. Various phytoestrogens may have very different effects on breast cancer. ENL may prove to be beneficial in breast cancer prevention strategies in the future while GEN may cause opposite effects.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5081.
Effect of exemestane on bone mineral density in postmenopausal women at increased risk for breast cancer.
Authors: Eng-Wong J , Reynolds JC , Venzon D , Wedam S , Prindiville S , Zujewski J , Korde L 
Published: December 2010

Abstract
Abstract #5086
Background: The aromatase inhibitors (AIs) show promise for breast cancer prevention in postmenopausal women. However these agents have been shown to decrease bone mineral density in women with breast cancer. Exemestane, a steroidal aromatase inhibitor, may be more bone sparing than the non-steroidal aromatase inhibitors.&#x2028; Methods: We conducted a phase II trial of exemestane in postmenopausal women at increased risk of breast cancer to assess the effect on anterior-posterior (AP) spine and total hip bone mineral density (BMD). Eligible participants are at increased risk for breast cancer by virtue of: Gail model risk &gt; 1.7% over 5 years; high risk pathological lesion (e.g. lobular neoplasia, ductal carcinoma in situ); known BRCA1/2 deleterious mutation or prior stage I/II breast cancer at least 2 years from breast cancer treatment and not treated with AIs. Women were required to undergo DEXA scan of the AP spine and hip at baseline and were excluded if AP spine T-score was ≤-2.5. AP spine measurements were done twice at each time point and the results averaged. Study participants receive exemestane 25 mg, calcium carbonate 1200 mg and vitamin D 400 IU daily for two years. We report the results of a planned interim safety analysis assessing one year change in bone density in the first 18 subjects. Student's t-test was used to determine relative change from baseline in AP spine and total hip BMD.&#x2028; Results: To date, 30 women have enrolled in the trial and 21 have completed 1 year of exemestane. Three women discontinued agent after an average of 3 months due to joint pain. For the 21 included in this analysis 15 were eligible due to a high risk pathological lesion, 4 by Gail Model and 2 by prior breast cancers. The average change in AP spine BMD from baseline to 1 year (N= 21) is –1.3 %, range -10.0 to +7.0% (p=0.20 for the null hypothesis of zero overall change; 95% C.I. for the mean -3.2% to +0.7%). Average AP spine T score is -0.28 at baseline and -0.45 at one year. Change in total hip BMD is -1.4%, range -7.5% to 5.9% (p=0.058, 95% C.I. -2.8% to +0.1%). Average total hip T score is -0.05 at baseline and -0.17 at one year.&#x2028; Conclusions: These preliminary data suggest that exemestane 25 mg/day for one year with concurrent calcium and vitamin D has acceptable effects on bone density in postmenopausal high risk women, although there were wide ranges in effects. The observed average reduction in BMD is less than the reported effect in treatment studies of women with invasive breast cancer. Studies are in progress to determine whether exemestane use by postmenopausal women is effective in reducing the risk of invasive breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5086.
Hormone therapy – who takes it – the rich or the poor?.
Authors: Massey EJ , Chaudhry A , Thomas R , Robert P , James B , Charlie C 
Published: December 2010

Abstract
Abstract #5093
Introduction: In the UK, hormone therapy is provided to all breast cancer patients for a standard NHS prescription charge (approximately USD13 per month). Previous studies in the USA and the UK have shown that only 60% of patients comply fully with prescribed therapy. This study examines the effects of age, drug type, prognosis and social deprivation on hormone therapy compliance.&#x2028; Method: During scheduled outpatient appointments data was collected from patients as part of their routine follow-up. Parameters included: age, name of drug, time on drug, drug compliance (full; deviation – missing &lt;1 pill/week; holiday – missing pills &gt; 1 week; stopped), and side effects (subjective – mild; moderate; severe). Prognostic information was derived using the Nottingham Prognostic Index (NPI). The patients' home postal codes were collected and allocated to the correct electoral ward (small geographical areas with average population of 5500). Using data from the UK National Census in 2000, information on social status was derived from the patients' postal codes and given as the Index of Multiple Deprivation (ID2000). The ID2000 has both an ID2000 score and ID2000 ranking (1 to 8414) for different electoral wards across England & Wales. Low ID2000 scores and high ID2000 rankings correspond to areas of affluence. Patients in ID2000 rankings &lt;4212 were assigned as 'deprived' and &gt;4212 as 'affluent'. The predominant social grade for each ward was recorded (AB, C1, C2, D and E).&#x2028; Results: To date, 117 patients have been analysed. The ID2000 ranks ranged from 1033 to 8297. Ninety two (89%) of patients were fully compliant, 5 (5%) deviated, 2 (2%) took a holiday and 4 (4%) stopped taking their hormone treatment. Compliance was significantly better for those taking an aromatase inhibitor (AI) (96.7%) than tamoxifen (80.5%) (Chi2 test Chi2 = 7.147. p = 0.0075). Compliance is unaffected by affluence (92.5%) v deprivation (80.9%) (Chi2 test Chi2 = 2.486, p=0.11). Compliance is also unaffected by NPI (Mann Whitney U test p=0.84) and age (Mann Whitney U test p=0.78).&#x2028; Conclusion: These early data suggest that hormone drug compliance in our centre is higher than previously reported. Compliance is significantly higher for aromatase inhibitors than tamoxifen; currently there is no discernable difference between individual AIs. Compliance appears higher in affluent patients; however this is not statistically significant. Compliance appears to be independent of age, duration of therapy and prognosis. This study is ongoing and further work comparing different areas is recommended.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5093.
Choosing breast reconstruction – for richer, for poorer?.
Authors: Roe T , Massey E , Chaudhry A , Price R , Chan C 
Published: December 2010

Abstract
Abstract #5094
OBJECTIVE&#x2028; To assess whether the age or socio-economic status of patients undergoing mastectomy play any part in influencing their decision to undergo breast reconstruction.&#x2028; METHODS&#x2028; Details were collated from all patients undergoing mastectomy with or without reconstruction under the care of a single surgeon at Cheltenham General Hospital over a 5 year period. All patients having a mastectomy were offered a reconstruction. Zip codes were used to assign government deprivation scores and the corresponding national rank for each patient's residential district, according to the 2000 UK national census. Affluent areas have low scores and high rank; deprived areas have high scores and low rank. The Mann-Whitney U test was used to determine whether there was a statistical difference in age or social status between those patients in the mastectomy only group and those who were reconstructed.&#x2028; RESULTS&#x2028; 50 patients underwent mastectomy only (median age 63.5, IQR 52-72), 30 opted for reconstruction (median age 53.5, IQR 44.5-58). There was a statistically significant difference (at the 95% confidence interval) between the average age of the 2 groups (P=0.0002).&#x2028; Median deprivation score for the mastectomy group was 10.4 (6.28-17.84) and for the reconstruction group 9.67 (6.52-17.37). This was not significant (P=0.26).&#x2028; Median ranks were 6224 (4008-7525) and 6511 (2502-7213) respectively (P=0.29).&#x2028; CONCLUSIONS&#x2028; The socio-economic status of patients does not affect their decision on whether or not to undergo post-mastectomy reconstruction. However, younger patients are statistically more likely to opt for a reconstructive procedure.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5094.
Racial disparities in breast cancer knowledge.
Authors: Petrak GA 
Published: December 2010

Abstract
Abstract #5099
Background: Many women fear breast cancer, but may know a great deal about the disease. We assessed the breast cancer attitudes and knowledge of women who self-identified as Caucasian, African American, Asian American, and Hispanic/Other.&#x2028; Methods: We created a survey to measure women's attitudes and knowledge regarding breast cancer. We surveyed women outside retail establishments in Michigan and Washington, DC. We obtained 160 responses. We analyzed the data using the students t-test for continuous variables and the chi-square test for categorical variables, with significance set at the 0.05 level.&#x2028; Results: The racal distribution was: Caucasian, N = 119 (74.4%); African American, N = 19 (12%); Asian American, N = 17 (11%); other, 4 (2.5%), one respondant did not state her race. We asked: (1) Have you ever had a mammogram? Caucasian, No = 38 (32%); African American, No = 6 (33%); Asian American, No = 13 (76%): P=0.007. (2) True/False: A mammogram does not use radiation to image the breast. Caucasian, False = 72 (64%); African American, False = 13 (76%); Asian American, False = 9 (56%): P = 0.07. (3) True/False: All women with breast cancer need chemotherapy. Caucasian, False = 88 (93%); African American, False = 11 (92%); Asian American, False = 10 (77%): P = 0.03. (4) True/False: All women who need chemotherapy receive it. Caucasian, False = 88 (93%); African American, False = 11 (92%); Asian American, False = 10 (77%): P = 0.04.&#x2028; Discussion: Caucasians and African Americans were very similar in their breast cancer knowledge, but Asian Americans were less likely to have had a mammogram, less likely to know about radiation and mammograms, less likely to believe that all women with breast cancer need chemotherapy, and more skeptical regarding whether women who need chemotherapy actually receive it.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5099.
The UK NIHR multicentre randomised COMICE trial of MRI planning for breast conserving treatment for breast cancer.
Authors: Drew PJ , Harvey I , Hanby A , Brown S , Olivier C , Napp V , Brown J , Turnbull LW , Trialists on Behalf of Comice 
Published: December 2010

Abstract
Abstract #51
The role of the addition of MR imaging (MRI) to routine techniques for loco-regional staging of primary breast cancer is unclear. The UK NIHR HTA multicentre COMICE trial considered whether adding an MRI scan to conventional triple assessment (mammogram, ultrasound and biopsy) assisted loco-regional staging and thereby reduced re-operation rates, for patients with primary breast cancer scheduled for wide local excision.&#x2028; The primary endpoint of the COMICE trial considered the proportion of patients undergoing a repeat operation or mastectomy at further surgery within six months of randomisation, or an avoidable mastectomy at initial surgery (re-operation rate). This was compared using logistic regression adjusting for age, breast density, and surgeon.&#x2028; Between December 2001 and January 2007 1625 patients were randomised to receive MRI (817) or not (808). Re-operation rate within six months (primary outcome) was 18.8% (MRI) and 19.3% (no MRI). No significant difference between the arms was detected (odds ratio=0.96, 95% CI=[0.75, 1.24], p=0.7691). Secondary endpoints included quality of life, imaging effectiveness and local recurrence.&#x2028; The results of the COMICE trial indicate no significant benefit in terms of reduction in re-operation rates, by the addition of MRI to conventional triple assessment for this patient group. These results have importance from both health economic and patient burden perspectives.&#x2028; This project was funded by the NIHR Health Technology Assessment (HTA) Programme (project number 99/27/05) and will be published in full in an HTA report.The view and opinions expressed therein are those of the authors and do not necessarily reflect those of the UK Department of Health.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 51.
Racial disparities in magazine coverage of mammography.
Authors: Petrak GA 
Published: December 2010

Abstract
Abstract #5100
Background: African-American (AA) women are diagnosed with breast cancer later, at a higher stage disease, and have a higher mortality than European-American (EA) women. AA women have a lower rate of mammography screening and this lower rate may account, in part, for AA women's more severe disease at diagnosis and higher mortality. One possible reason for this racial disparity in mammography screening may be that AA women receive a different message than EA women from mass circulation magazines about mammography.&#x2028; Material and Methods: A computer-aided content analysis was performed of AA and EA women's magazines with a circulation of greater than one million that contained at least 1,000 words across all the mammography-related articles or sections of articles that were published between January 1, 2002 and December 31, 2007. The words that shared similar meanings were grouped into seven categories: (1) religiosity, (2) activity, (3) positive and (4) negative emotions, (5) medical terms, (6) risk factors, (7) race portrayed, by which is meant when race was noted in articles as African American/Black or European American/White. The frequencies of each word were counted across all articles by type of magazine, i.e., predominately AA readers and EA readers. The Pearson product-moment method was used to calculate correlations, the Student's t-test was used for correlated samples to compare the means of the continuous variables, and McNemar's test was used to assess the difference between two correlated proportions. Significance was set at the 0.05 level.&#x2028; Results: The magazines that met the study criteria were the African-American magazines Ebony and Essence and the European-American magazines Good Housekeeping, Marie Claire, Redbook, and Vogue. The six magazines yielded the following total number of words per magazine that focused on mammography: (a) Ebony: 17,221 words, (b) Essence: 20,257 words, (c) Good Housekeeping: 12,998 words, (d) Marie Claire: 7,654 words, (e) Redbook: 29,201 words, and (f) Vogue: 11,482 words. The word categories were compared in terms of their relative word frequencies, AA and EA.&#x2028; &#x2028; Discussion: There were clear differences in the mammography messages presented in the AA and the EA magazines. The AA magazines contained more references to religiosity, activity, positive and negative emotions, and risk. It was striking that racial references to African Americans were ubiquitous in the African-American magazines, whereas, racial references to either African Americans or European Americans were almost completely absent from the European-American magazines.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5100.
Clinical impact of pathological axillary downstaging in locally advanced breast cancer after primary systemic chemotherapy.
Authors: Zambetti M , Bianchini G , Bianchi G , Mariani G , Moliterni A , Mariani P , De Benedictis E , Valagussa P , Greco M , Gianni L 
Published: December 2010

Abstract
Abstract #5103
Background Primary Systemic Chemotherapy (PSC) can result in pathologic axillary downstaging even in Locally Advanced Breast Cancer (LABC), which is generally associated with unfavorable prognosis and high incidence of nodal metastases. Aims were to evaluate: the clinical and biological factors associated with the likelihood of obtaining negative pathological nodes (pN0); the relationship between outcome and axillary nodal status at diagnosis (cN) and at surgery after PSC (pN).&#x2028; Methods Women with LABC consecutively treated at the Istituto Nazionale Tumori in Milan from 1991 to 2007 were evaluated. Patients received PSC containing Doxorubicin ± Paclitaxel (+ adjuvant or neoadjuvant CMF) and endocrine therapy ± trastuzumab. Fixed right-censoring at 5 years was performed. Associations with Disease-Free Survival (DFS) and Overall Survival (OS) were evaluated using Kaplan-Meier (log-rank test) and Cox regression analysis. All confidence intervals are at 95%.&#x2028; Results 451 women submitted to surgery and complementary RT were included in the analysis. 68% of surviving patients were followed for at least 5 yrs. 5y-DFS and OS were 51% (46-57%) and 70% (65-75%) respectively. ER negative, PGR negative, high grade and age &lt;50 yrs were correlated with likelihood of pN0 at univariate logistic analysis, while ER negative only (OR 3.49, CI 1.65-7.66; p=0.001) retained significant role in the multivariate analysis.&#x2028; Relationship between axillary status and outcome are shown in table 1.&#x2028; &#x2028; Multivariate Cox regression analysis showed that positive nodes at diagnosis (HR 2.13, CI 1.07-4.22; p=0.03) and at surgery (2.84, CI 1.77-4.56; p&lt;0.001), negative PGR (HR 1.79, CI 1.12-2.86; p=0.01), inflammatory status (HR 1.51, 1.02-2.23; p=0.04) and age &lt; 50 yrs (HR 2.23, CI 1.58-3.16; p&lt;0.001) were independent predictors of DFS. Multivariate analysis for OS demonstrated positive nodes at surgery (HR 3.46, 1.80-6.67; p&lt;0.001), negative PGR (HR 2.21, CI 1.16-4.20; p=0.01) and age &lt; 50 yrs (HR 2.00, CI 1.26-3.17; p=0.003) as significant variables. Pathologic complete response in breast was not significant in both multivariate analysis.&#x2028; Conclusions Axillary downstaging was obtained in a significant proportion of patients with LABC. pN0 status after PSC identifies a clinical subgroup with better prognosis irrespectively of locally advanced disease and, in this subgroup of patients, it is a prognostic factor stronger than pathologic complete response in the breast.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5103.