bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of tumor-specific HMG-CoA reductase expression in primary breast cancer.
Authors: Borgquist S , Jögi A , Pontén F , Ryden L , Brennan D , Jirström K 
Published: December 2010

Abstract
Abstract #5071
Background&#x2028; We have previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-term follow up.&#x2028; Methods &#x2028; The expression of HMG-CoAR was assessed by immunohistochemistry (IHC) on tissue microarrays with tumour specimens from 498 consecutive breast cancer cases with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free and breast cancer specific survival.&#x2028; Results &#x2028; In line with our previous findings, tumour-specific HMG-CoAR expression was associated with, low grade (p &lt;0.001), small (p = 0.007), ERα positive (p =0.01), Ki-67 negative (p =0.02) tumors. Patients with tumours expressing HMG-CoAR, had a significantly prolonged disease-free-survival, also when adjusted for established prognostic factors; RR= 0.60, 95% CI (0.40-0.92); p=0.02. In estrogen receptor negative tumours, however, there was a trend, however non-significant, towards a shorter DFS in HMG-CoAR expressing tumours.&#x2028; Conclusion&#x2028; HMG-CoAR expression is an independent predictor of a prolonged disease-free-survival in primary breast cancer. This may, however, not be true for ERα negative tumours. Further studies are needed to shed light on the value of HMG-CoAR expression as a surrogate marker of response to statin treatment, especially with respect to hormone receptor status.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5071.
JNK, essential for anticancer therapy-induced apoptosis, promotes breast cancer progression.
Authors: Wang J , Kuiatse I , Casa AJ , Lee AV , Cui X 
Published: December 2010

Abstract
Abstract #5075
The c-Jun N-terminal kinase (JNK) is a critical mediator of stress-induced apoptosis and is required for the cytotoxic effect of anticancer therapies. Interestingly, recent clinical studies showed that high JNK activity is associated with poor prognosis in human breast cancer. The molecular basis of this potential dual function of JNK in breast cancer is poorly understood. Here we report that overexpression of a constitutively active JNK in breast cancer cells increased cell migration and invasion. In agreement with this, fibroblast-specific markers like the intermediate filament vimentin and the extracellular matrix protein fibronectin were up-regulated. AP-1 transcription factor, which induces expression of these two proteins, was markedly increased by JNK overexpression. In addition, hyperactive JNK reduced Akt1 activation but enhanced Erk activation in breast cancer cells. In relevance, we also found that JNK levels are significantly higher in invasive breast cancers including those with distant metastases (n = 235, p &lt; 0.0001, Wilcoxon rank sum test) than in normal breast tissues (n = 69). Most surprisingly, an increase of JNK attenuated the apoptosis of breast cancer cells treated with chemotherapy drugs doxorubicin and taxol. This suggests that the role of JNK changes when its activity/expression increases above the basal levels associated with apoptosis. Our data, together with a recent finding that cells undergoing cytotoxic agent-induced apoptosis can induce compensatory hyper-proliferation of proximal cancer cells, suggest a novel mechanism of breast cancer therapeutic resistance. Therapy-elicited apoptosis of tumor cells with basal JNK activity may release mitogens that induce hyperactive JNK in neighboring cells to promote growth and invasion. Thus JNK activation may serve as a marker of breast cancer progression.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5075.
Levels of 25-hydroxy-vitamin D in pre-menopausal women at high risk for development of breast cancer.
Authors: Fabian CJ , Kimler BF , Phillips T , Zalles CM 
Published: December 2010

Abstract
Abstract #5079
Background: There is biologic and epidemiologic evidence to suggest an inverse relationship between vitamin D intake and the risk of developing breast cancer, particularly for adolescent and premenopausal women. A recent meta-analysis of nested case control studies in an average risk cohort has suggested that those with &gt;50 ng/ml of the pro-hormone 25-hydroxy-vitamin D, 25(OH)D, a good measure of recent vitamin D intake from all sources, have 50% fewer breast cancers than women with 25(OH)D levels regarded as severely deficient (&lt;12 ng/ml) and 20% fewer breast cancers than those with levels regarded as deficient (12-20 ng/ml) or insufficient (20-30 ng/ml) [Garland et al. J Steroid Biochem Mol Biol 2007;103:708].&#x2028; Materials and Methods: To determine if vitamin D supplementation should be explored as a prevention strategy in young women, we assessed the distribution of 25(OH)D levels in 100 high risk pre-menopausal women being screened for possible participation in Phase II prevention trials of a COX-2 inhibitor. These women were between the ages of 20 and 52, had undergone a random periareolar fine needle aspiration (RPFNA) and had serum frozen at -80°C within 2 months of the RPFNA. Serum was batch assayed for 25(OH)D, using the Liaison kit by DiaSorin (chemiluminescent assay) in a CLIA approved lab.&#x2028; Results: Of 100 high risk women, 15% exhibited 25(OH)D levels considered severely deficient, 34% deficient, and 27% insufficient, Only 24% women exhibited 25(OH)D levels above 30 ng/ml, considered to be sufficient for bone health while only 4% had levels suggested as optimal for breast health. We have previously reported that high risk women with cytologic evidence of atypia had a 5 fold increase in their 4 year risk of developing DCIS or invasive cancer compared to those who do not [Fabian et al. J Natl Cancer Inst 2000; 92:1217]. Ninety-nine percent of women in our cohort were considered to have cytologic evidence of hyperplasia without (70%) or with (29%) atypia and median 25(OH)D levels were not different between samples regarded as hyperplastic and those assessed as atypical.&#x2028; Discussion: These results indicate that 75% of high risk pre-menopausal women likely to participate in tissue biomarker-based chemoprevention trials will exhibit 25(OH)D levels that are insufficient for bone health and only 4% will have levels suggested from case control studies as being optimal for breast health. In this retrospective study, no association was observed between serum 25(OH)D levels (a marker of recent vitamin D intake) and a cytologic marker of increased breast cancer risk. A prospective trial is in progress to confirm the high prevalence of vitamin D insufficiency in young high risk women and to correlate 25(OH)D levels with a variety of tissue, imaging and serum-based risk biomarkers.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5079.
Comparison of weight loss with a National Cancer Institute diet and a plant-based olive oil diet in overweight women with invasive breast cancer.
Authors: Flynn MM , Fenton M 
Published: December 2010

Abstract
Abstract #5080
Background: Breast cancer risk increases with increasing body weight, higher blood levels of fasting insulin and triglycerides, and lower HDL-c. Weight loss and diet can affect these variables. Lower fat diets are routinely recommended for weight loss and cancer prevention, yet no firm evidence indicates an advantage compared to moderate fat diets. Further, lower fat diets can adversely affect fasting blood levels of insulin, triglycerides and HDL-c.&#x2028; Methods: Overweight women diagnosed with invasive breast cancer after the age of 50 consumed a National Cancer Institute diet (NCI; total fat: &gt;15% to &lt;30%) and a plant- based, olive oil diet (PBOO; total fat: &gt;35%, primarily from extra virgin olive oil) for 8 weeks each in a crossover trial with random assignment to order. Fasting blood samples at the end of each diet were analyzed for insulin, triglycerides and HDL-c.&#x2028; Results: Results for 20 subjects. Percent weight loss (NCI: 4.2+1.9; PBOO: 5.6+2.2) in this preliminary group exhibited a significant diet-order effect.&#x2028; &#x2028; Conclusion: These initial results suggest that weight loss can be achieved with a plant- based, higher- fat diet emphasizing extra virgin olive oil, and such a diet may have a metabolic advantage compared to the standard, lower-fat diet. This study was funded by Susan G. Komen for the Cure Grants Program.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5080.
Postmenopausal hormone therapy in a prospective randomized trial of termination versus long-term continuation results in greater regional brain metabolism.
Authors: Silverman DH , Geist CL , Kenna HA , Rasgon NL 
Published: December 2010

Abstract
Abstract #5088
Objective: Beyond the potential effects of sex steroids on the risk of developing breast and other cancers, the effect of postmenopausal hormone therapy on human brain aging and cognition is also currently highly controversial. In a prospective study of women at increased risk for developing Alzheimer disease (AD), we examined the influence of exogenous and endogenous estrogen exposure on regional cerebral metabolism. Methods: Women on postmenopausal hormone therapy (HT) and at increased risk for AD were randomized to immediately terminate or continue HT. Of 81 total subjects studied to date, data from the first 25 consecutive subjects to complete the 2-yr protocol are presented. Subjects in each randomized arm were similar in average yrs of education (16.5 vs. 16.6), age at menarche (13.1 vs. 12.6), age at menopause (47.3 vs. 47.9), and age at recruitment (58.4 vs. 58.9). All subjects underwent FDG-PET imaging at baseline as well as 2 yrs after randomization, and scans were assessed for interactions of time-, exogenous therapy arm-, and endogenous hormonal covariate-based effects, with statistical parametric mapping. Results: Across all subjects, yrs of endogenous estrogen exposure (age at menopause minus age at menarche) positively correlated most significantly (t=4.23,p&lt;0.0005) with metabolism of the precuneus area of the posterior medial cortex (area where perfusion is most significantly diminished in early stages of AD), which is consistent with experimental animal and human epidemiologic data supporting a neuroprotective role for estrogen. Two years after termination of HT, subjects demonstrated a highly significant negative correlation (t=-9.27,p&lt;0.0005) of yrs of endogenous exposure with metabolism of anterior medial frontal cortex (area of the brain undergoing the most significant decline of perfusion and metabolism with normal aging), suggesting that the levels of frontal metabolism reached during the years of greater endogenous exposure were more rapidly lost during 2 yrs of estrogen deprivation. Moreover, those women who continued HT during the 2 yr interval of randomization, actually demonstrated a significant increase in the most anterior portion of their medial prefrontal cortex during that period (t=5.06,p&lt;0.0005), while those women who discontinued HT did not, and this part of the brain was the location of the largest increase over 2 yrs (4083 contiguous voxels having signigicance of p&lt;0.01) throughout the brain. Conclusion: Both exogenous and endogenous hormone exposure were associated with changes in medial cortical metabolism consistent with neuroprotective roles relevant to metabolic changes occurring in brain aging and dementia.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5088.
Day surgery for breast cancer: a pilot randomised controlled trial.
Authors: Marla S , Proctor M , Romics L , Ogston K , Cooke T , Stallard S 
Published: December 2010

Abstract
Abstract #5090
Background: Over the past 10 years, surgical management of Breast Cancer has undergone a huge change. More patients are now treated by breast conserving surgery (BCS) and lesser axillary surgery. Therefore, great potential exists to carry out Breast Cancer surgery in day surgery (DS) setting. However, at present few centres in the United Kingdom are practicing this.&#x2028; The objectives of the present study were: (i) to review the evidence in literature, (ii) analyse current practice and (iii) conduct a pilot randomised controlled trial (RCT) comparing DS and inpatient surgery (IS) for patients undergoing BCS for Breast Cancer.&#x2028; Methods:&#x2028; (i) A systematic review of literature searching DS for breast cancer was performed using standard search tools.&#x2028; (ii) Age, treatment and length of stay information about all breast patients admitted at a tertiary centre from March, 07 to Jan, 08 was prospectively collected.&#x2028; (iii) Newly diagnosed breast cancer patients undergoing BCS with axillary sampling who had passed the DS preassessment were randomised to DS or IS. Physical and psychosocial outcomes were assessed using a Surgical Site Infection Form (Day 7 and Day30), FACT-B questionnaire (Baseline, Day7 and Day30) and a Patient Diary for the first post-operative week.&#x2028; Results:&#x2028; (i) No RCTs were found in the literature. Ten observational studies describing DS for breast cancer were included. Seven of these found DS to be safe with equivalent complications to IS and 3 highlighted its economic benefits. Only 1 study used a validated psychological distress scoring system and found results in favour of DS.&#x2028; (ii) Over the 10-month period there were 288 breast cancer operations. Of these, only 112 (38.9%) stayed in the hospital for &gt; 23 hours. Hence, it would be ideal to consider breast cancer for DS.&#x2028; ((iii) There were 18 patients in the pilot RCT; 11 in the DS arm and 7 in the IS arm.&#x2028; Physical outcomes: There were no significant differences in pain, nausea or vomiting scores and infection rates. Patients in the DS group mobilised and stepped out of their house earlier (Day2 vs. Day4) after surgery and also more frequently (4 days vs. 3 days) in the first week than the IS group.&#x2028; FACT-B: Longitudinal differences in overall FACT B scores obtained on Day 7 and Day 30 compared to Baseline scores are detailed in Table1. A difference of &gt; 5% was considered significant.&#x2028; &#x2028; Conclusions: Systematic review of literature showed DS to be safe for the patient but there is lack of evidence in the form of RCTs.&#x2028; This pilot RCT shows that DS patients mobilise earlier and have equivalent results for the other physical outcomes. FACT-B scores suggest better quality of life a week after surgery in the DS group.Larger RCTs are needed to support these results.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5090.
Choosing chemotherapy: who says “yes please”?.
Authors: Price RK , Morgan CZ , Roe T , Massey E , Chaudry A , Jenkins* P , Bristol JB , Chan CH 
Published: December 2010

Abstract
Abstract #5091
Introduction:&#x2028; Increasing numbers of patients are being offered adjuvant chemotherapy for early breast cancer. In the United Kingdom, the National Health Service provides cancer treatment free at the point of delivery. So what makes people decide whether to have chemotherapy?&#x2028; Methods:&#x2028; We examined the decision made by patients treated in our centre in 2007. Data were obtained from our prospectively collected database about age, prognosis (Nottingham Prognosis Index/Score - NPI), ER, HER2 status, and residential ZIP code. The UK Government Index of Multiple Deprivation (ID2000, Office for National Statistics) is based on the 2000 national census and provides two measures, the ID 2000 score and the ID2000 Rank (1 to 8414 in England and Wales). We matched ID2000 scores and ranks to ZIP codes. Low ID2000 scores and ranks are seen in affluent areas. Chemotherapy uptake was examined by age, NPI, ER, HER2 status and ID2000 using Stat View 5.0® software (SAS Institute).&#x2028; Results:&#x2028; 282 patients (279 women and 3 men) with invasive breast carcinoma were treated in 2007 at our centre. 135 (47.9%) were offered chemotherapy. 103/135 (76.3%) decided to have chemotherapy and 32/135 (23.7%) declined.&#x2028; Chemotherapy was more commonly accepted by patients of young age (Mann Whitney U, p=0.0003), high NPI (Mann Whitney U, p=0.0012) and with HER2 positive tumours (Chi2 test, p=0.05). ER status (Chi2 test, p=0.27) and deprivation (Mann Whitney U, ID2000 score p=0.46, ID2000 rank p=0.46) had no effect on whether patients chose to have chemotherapy.&#x2028; Conclusion:&#x2028; Significant numbers of patients are now being offered adjuvant chemotherapy. Most patients accept chemotherapy when this is offered, although a significant minority (23.7%) decline the offer. Younger patients and those with poorer prognosis are more likely to accept this. Social deprivation, however, is not an influence in patient choice, when the patient has care 'free at the point of delivery'.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5091.
Influence of private practice setting on adjuvant chemotherapy use for elderly women with early-stage breast cancer.
Authors: Hershman DL , Buono D , McBride RB , Tsai W , Neugut AI 
Published: December 2010

Abstract
Abstract #5096
Background:&#x2028; For elderly women with breast cancer (BC), the decision to undergo treatment with adjuvant chemotherapy may be associated with non-medical factors, such as physician and practice characteristics. Since physicians influence medical decision-making, we evaluated the association between oncologist characteristics and receipt of adjuvant chemotherapy in elderly women at both high and low-risk for breast cancer recurrence.&#x2028; Methods:&#x2028; We used the SEER-Medicare database to identify women &gt;65 years, diagnosed with stages I-III BC, between 1992-2002, and used the Physician Unique Identification Number linked to the American Medical Association Masterfile to obtain information on oncologists. We investigated the association of patient demographic, tumor, and oncologist-related factors with receipt of chemotherapy for both women with high and low risk of recurrence, using Generalized Estimating Equations to control for clustering. We defined patients as low-risk who had hormone sensitive, stage I/II cancer, and high-risk if they were hormone receptor negative and stage II/III.&#x2028; Results:&#x2028; Of 42,544 women with stage I-III BC, 8,714 (20%) were treated with adjuvant chemotherapy. The proportion of women with high-risk tumors treated was 61% while the proportion with low risk cancers was 15%. Patients who received chemotherapy were younger, of higher SES, and had less favorable tumor characteristics. They were also more likely to be married, diagnosed more recently and have fewer comorbid conditions. In a multivariable analysis, women who underwent chemotherapy were more likely be treated by an oncologists who was primarily employed in a private practice (OR=1.40; 95%CI 1.23-1.59), and completed training after 1975 (OR=1.12; 95%CI 1.01-1.26), and were less likely to have an oncologist who trained in the United States (OR=0.83; 95%CI 0.74-0.93), than oncologists of patients who did not receive chemotherapy. The association between oncologists in private practice and receipt of chemotherapy was slightly stronger for patients who were at high-risk (OR=1.55) than those for low-risk (OR=1.35) for cancer recurrence.&#x2028; Conclusions:&#x2028; After controlling for confounding variables, elderly women with both high risk and low risk BC treated by oncologists who were primarily employed in a private practice were more likely to receive adjuvant chemotherapy. Other oncologists characteristics, such as gender, patient volume and type of degree were not independent predictors of receipt of chemotherapy. Efforts to differentiate whether these associations reflect experience, practice setting, insurance type, or other economic incentives are warranted.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5096.
Preliminary findings from a patient navigator program with Hispanic women from community clinics in South Texas.
Authors: Ramirez AG , Gallion KJ , Miller AR , Velez LF , San Miguel de Majors SL , Falkenberg M , Covarrubias SV , Munoz E 
Published: December 2010

Abstract
Abstract #5097
A patient navigator program that uses a trained community health worker to assist Hispanic women in utilizing cancer care services has been successfully implemented in South Texas for the past two years. The objectives of this program are to 1) reduce the rate of noncompliance after reception of abnormal breast and cervical cancer screening results, which will in turn reduce the time between screening and the commencement of treatment, and 2) improve patient satisfaction with the health care system experience. Participants include low-income Hispanic women who receive abnormal breast and/or cervical cancer screening results from two community clinics, a Treatment and a Comparison clinic. Participants from both clinics are administered a pre-(baseline) and a post-survey. The pre-survey is administered upon recruitment into the study, and the post-survey is administered six months after the baseline survey. Clinical data about participants' abnormal screening results are also extracted from their medical records. In addition, a patient navigator facilitates scheduling clinic visits, resolving medical problems and avoiding non-medical delays in evaluation for patients participating in the Treatment Arm. This session will present preliminary results, lessons learned, common patient barriers and strategies to address the barriers.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5097.