bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-12-03: A pilot study evaluating the benefits and feasibility of an exercise program for breast cancer patients receiving adjuvant chemotherapy.
Authors: Petrella TM , Laredo S , Oh P , Marzolini S , Warner E , Dent R , Verma S , Eisen A , Pritchard K , Trudeau M , Zhang L , Bjarnason G 
Published: August 2014

Abstract
BACKGROUND: Breast cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, muscle strength and quality of life (QOL). Evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining QOL, cardiorespiratory fitness and strength, however the results of studies conducted to date have not been consistent.
OBJECTIVES: This study aimed to determine the effect of a structured, tailored exercise program involving both aerobic and resistance training, on QOL, physical function, and body composition in breast cancer patients undergoing adjuvant chemotherapy.
METHODS: Women who were within 4–12 weeks of surgery for stage I-III breast cancer and undergoing adjuvant chemotherapy, were randomized to either a structured exercise program (6 months) or to usual oncology care. Functional assessment of cancer therapy-breast cancer (FACT-B), and Short Form Survey (SF-36), weight, waist circumference, waist hip ratio, percent body fat, peak oxygen, strength and arm volume were performed at baseline, and 3-month intervals through 12 months. One-way analysis of variance (ANOVA) was performed at baseline, 3, 6 and 12 months for all endpoints. The Wilcoxon Rank-sum Nonparametric test was applied for all Primary and Secondary endpoints with changing scores at each follow-up visit, p-value &lt; 0.05 was considered as statistical significance.
RESULTS: Of the recruited 62 women, 51 completed all 12 months. One patient developed metastatic disease and 10 others withdrew (4 in the exercise arm and 6 in the standard arm). Median age was 48 (24–75) years. There was a general trend of improvement from baseline for most components of the FACT-B and SF-36 for the exercise group but only the FACT-B social wellbeing was statistically significant at 3 months with a p = 0.0164. Changes in other FACT-B and SF-36 scores were not significantly different between exercise and usual care groups. There were significant improvements at 6 months in weight (p = 0.0192), % body fat (p = 0.0337), max strength (p = 0.0029), and waist circumference (0.0359) and at 12 months in weight (p = 0.0293), % body fat (p = 0.0481), max strength (p = 0.0097) and endurance (p = 0.0037) in the exercise group compared to usual care.
CONCLUSIONS: This randomized prospective study suggests benefit of exercise during chemotherapy. This benefit continued 6 months beyond the completion of the exercise program with significant improvement in physical function, body composition, strength and endurance with no decline in quality of life. Regular moderate exercise may play an important role in improving function during adjuvant chemotherapy and should be further studied in a large randomized trial.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-03.
Abstract P2-12-09: A randomized controlled trial of support group intervention after breast cancer treatment: Results on sick leave, health care utilization and health economy.
Authors: Granstam Björneklett H , Rosenblad A , Lindemalm C , Ojutkangas M-L , Letocha H , Strang P , Bergkvist L 
Published: August 2014

Abstract
Background: More than 50% of breast cancer patients are diagnosed before the age of 65. Returning to work after treatment is, therefore, of interest for both the individual and society. The aim was, therefore, to study the effect of support group intervention on sick leave, health care utilization and health economy.
Material and Methods: Of 382 patients with newly diagnosed breast cancer, 191 + 191 patients were randomized to an intervention group or to a routine control group respectively.
The intervention group received support intervention on a residential basis for one week, followed by four days of follow-up two months later. The support intervention included informative-educational sections, relaxation training, mental visualization and non-verbal communication. Patients answered a questionnaire at baseline, 2, 6 and 12 months about sick leave and health care utilization.
Result There was a trend towards longer sick leave and more health care utilization in the intervention group. The difference in total costs was statistically significantly higher in the intervention group after 12 months (p = 0.0036)
Conclusion There was no economic benefit from intervention in its present form. In fact we saw a tendency towards longer sick leave and more health care utilization and we could show that the total cost in the intervention group was actually higher and that this difference was statistically significant after twelve months.
Key words: Support intervention, breast cancer, return to work, sick leave, health care utilization, health economy
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-09.
Abstract P2-13-09: Pharmacological impact of endoxifen in a laboratory simulation of tamoxifen therapy in postmenopausal breast cancer patients
Authors: Maximov PY , McDaniel RE , Bhatta P , Brauch H , Jordan VC 
Published: August 2014

Abstract
Tamoxifen is a well-established adjuvant drug for the treatment and prevention of Estrogen Receptor (ER) positive breast cancer, effective in both pre- and postmenopausal women. However, the metabolic activation of tamoxifen to endoxifen by the CYP2D6 enzyme system still remains controversial to plan the treatment of patients with breast cancer. Since the discovery and description of the pharmacological properties of endoxifen, clinical trials were undertaken to determine the pharmacological relevance of endoxifen. The results of these trials, however, vary. In this study we demonstrate the pharmacological impact of endoxifen in a laboratory simulation of breast cancer therapy with tamoxifen in postmenopausal women in vitro in a panel of human breast cancer cell lines (MCF-7, T47D, ZR-75-1 and BT474). The concentrations of estrogens (E1/E2) used to simulate postmenopausal women treated with tamoxifen, were obtained from published studies, as well as the concentrations of tamoxifen and its metabolites (N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen) based on the CYP2D6 genotype in postmenopausal breast cancer patients (Murdter TE et al, Clin Pharmacol Ther, 2011). Our results demonstrate that irrespective of CYP2D6 genotype, tamoxifen and its primary metabolites (N-desmethyltamoxifen and 4-hydroxytamoxifen) are able to inhibit completely the estrogen-stimulated growth of breast cancer cells in vitro. Additional endoxifen in any concentration corresponding to CYP2D6 genotype was not able to increase the antiestrogenic effect of tamoxifen and its primary metabolites. Moreover, we demonstrate that 4-hydroxytamoxifen is absolutely essentialforinhibition of estrogen action. Based on our results, we can conclude that endoxifen is pharmacologically supportive but not essential for any genotype of CYP2D6 in a postmenopausal setting. This study (PYM) was supported by Susan G. Komen for the Cure International Postdoctoral Fellowship under Award number SAC100009(VCJ), and the Department of Defense Breast Program under Award number W81XWH-06-1-0590 (VCJ).
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-09.
Abstract P3-01-01: Insulin, Insulin-like Growth Factor-1 and cycling estrogen predict premenopausal mammographic density.
Authors: Frydenberg H , Flote VG , Iversen A , Finstad SE , Furberg A-S , Fagerland M , Wist EA , Schlichting E , Ellison PT , McTiernan A , Ursin G , Thune I 
Published: August 2014

Abstract
Background: Mammographic density, a strong biomarker for breast cancer risk, represents epithelial and stromal proliferation. Insulin and insulin-like growth factor (IGF)-1 are suggested to influence cellular proliferation, while estrogen is a key factor in breast cancer development. However, whether the effects of these hormones among premenopausal women are mediated through mammographic density is less known.
Material and Methods: Fasting serum insulin, IGF-1, and IGF binding protein (IGFBP)-3 were assessed among 202 healthy premenopausal women (Norwegian Energy Balance and Breast cancer Aspects study-I (EBBA-I). Daily salivary levels of 17β-estradiol throughout an entire menstrual cycle were measured at the reproductive Ecology Laboratory, Harvard University, USA. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms taken at day 7–12 of the menstrual cycle. Uni- and multivariable regression models were used to study the associations between hormones and premenopausal percent mammographic density.
Results: Among women with a mean age of 30,7 years, a mean premenopausal percent mammographic density of 29.8 % was observed. Throughout the menstrual cycle when comparing women with a high percent mammographic density (≥28.5%) to women with a low percent mammographic density (&lt;28.5%), we observed insulin, IGF-1 and IGFBP-3 independently and in combination with cycling 17β-estradiol to predict premenopausal percent mammographic density. We observed among women with either serum insulin ≥89 pmol/, IGF-1 ≥24 nmol/l, IGFBP-3 ≥ 100 nmol/l, having a high (≥28.5%) versus a low (&lt;28.5%) percent mammographic density was associated with an increase in overall average 17β-estradiol of 4.0 %, 10.9 % and 14.9%, respectively. Moreover, we observed a higher adjusted Odds Ratio (OR) for having a high percent mammographic density for each standard deviation (SD) increase in overall average 17β -estradiol, insulin, IGF-1 and IGFBP-3: 17β-estradiol, 1.55 (1.06–2.27); insulin, 1.62 (0.76–3.48), IGF-1, 1.90 (1.10–3.27); IGFBP-3, 1.88 (1.05–3.37) (adjusted for age, body mass index-BMI kg/m2)).
Conclusion: Our study supports that insulin, IGF-1 and IGFBP-3 independently, and in combination with cycling estrogen, predicts premenopausal mammographic density. These hormones may be important biomarkers in breast cancer control and clinical practice.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-01.
Abstract P3-02-03: Increased risk of breast cancer in women with false-positive screening test: can it be entirely explained by misclassification?
Authors: von Euler-Chelpin M , Kuchiki M , Vejborg I 
Published: August 2014

Abstract
Background: Screening for disease in healthy people inevitably leads to some false-positive tests. A recent study (von Euler-Chelpin et al, JNCI 2012) showed that women with a false-positive test from screening with mammography had an increased risk of being diagnosed with breast cancer later in life as compared to women with only negative results (RR = 1.67, 95% CI 1.45 to 1.88). The reasons for this excess risk remain unknown. In the present study we have assessed misclassification and evaluated the impact of misclassification on over all excess risk.
Method: We used data from the population-based screening mammography program in Copenhagen, Denmark, and studied 295 women exposed to a false-positive test that later developed breast cancer. Screening took place between 1991 and 2006, with a follow-up for cancer until 2008. Cancers that developed in the same location as the finding that initially caused the recall were defined as misclassified and excluded in the assessment of the excess risk among the false-positives. Time from diagnosis, breast density, tumor size, receptor and nodal status were also taken into account.
Results: 72 cases were found to be misclassified. When the misclassified tests had been excluded, we still found a significant excess risk for breast cancer of 27% (RR = 1.27, 95% CI (1.11 to 1.46) among the women with a false-positive test compared to women with only negative tests. Women with a false-positive test proven at assessment (Type 1) had an excess risk of 27% (RR = 1.27, 95% CI (1.09 to 1.46), while false-positives proven at surgery (Type 2) had an excess risk of 30 % (RR = 1.30, 95% CI (0.86 to 1.96). In the group of women with misclassified tests there were a significantly higher proportion of breasts with fatty tissue (BI-RADS density classification 1 or 2) than among the non-misclassified. The average time from first false-positive test to time of diagnosis was significantly shorter among women with misclassified tests, 4.0 years versus 7.8 years (p &lt; .0001). There were no significant differences in tumor size, receptor or nodal status.
Conclusion: The results indicate that the increased risk can not be explained only by misclassification. The excess risk remains for both Type1 and Type 2 false-positives, which favors some biological susceptibility, as women with false-positive test Type 2 have undergone surgery, which thus makes residual misclassification unlikely.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-03.
Abstract P3-02-10: Implementation and uptake of a provincial, population-based, organized breast screening program for high risk women in Ontario: The Ontario breast screening program (OBSP) high risk program.
Authors: Eisen A , Carroll J , Chiarelli AM , Horgan M , Meschino W , Rabeneck L , Shumak R , Warner E 
Published: August 2014

Abstract
Background: Genetic testing for mutations in BRCA1/2 has been clinically available in Ontario since 2000. Over 15000 individuals have been tested. Evidence from clinical trials has consistently shown that women at high risk of breast cancer (BrCa) benefit from BrCa screening that includes both magnetic resonance imaging (MRI) of the breast and mammography, yet access to MRI in Ontario was variable. In 2011, Cancer Care Ontario (CCO) established an expert panel to develop a protocol for expanding the OBSP, initially created for average risk women 50–74, to include MRI and mammography for eligible high risk women.
Methods: The panel's tasks included: 1. determining high risk criteria 2. estimating the prevalence of high risk women 3. selecting a cancer risk model 4. developing a referral and assessment pathway for potentially eligible subjects 5. developing educational resources, training plan and communication strategy for relevant stakeholders 6. developing indicators for program evaluation, 7. providing guidance for post-implementation issues.
Results: The program was initiated July, 2011 and now includes 28 sites. Women aged 30–69 with and without a history of breast cancer are eligible if they 1. are BRCA1/2 mutation carriers or untested first degree relatives of carriers, 2. have a lifetime risk of breast cancer &gt;=25% based on family history according to IBIS or BOADICEA risk models, or 3. received prior radiation therapy to the chest. It is estimated that 34000 high risk women in the target age group live in Ontario. Preliminary volume data for the first 9 mos are shown in Table 1. Of the 5037 women participating, 802 have been referred directly by their physician and 4,235 have been referred for genetic assessment. Of the 2,946 women who received genetic assessment, 31% met the high risk criteria. To date, 729 high risk MRI scans have been performed.
Conclusions: A population based organized screening program for high risk women that includes genetic risk assessment has been implemented in Ontario. Further evaluation of risk assessment and screen results are underway. To our knowledge, this is the first organized screening program for women at high risk of breast cancer.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-10.
Abstract P3-06-18: Increase of serum androgen and its metabolites in postmenopausal primary breast cancer patients with disease progression during neo-adjuvant exemestane treatment; JFMC 34–0601 TR
Authors: Takada M , Saji S , Honma N , Masuda N , Yamamoto Y , Kuroi K , Yamashita H , Ohno S , Aogi K , Ueno T , Toi M 
Published: August 2014

Abstract
BACKGROUND: We reported a positive correlation between body mass index (BMI) and clinical response to neo-adjuvant hormonal therapy (NAH) with steroidal aromatase inhibitor, exemestane, in post-menopausal breast cancer patients (Takada M et al. Breast 2012). Here, we examined the relationship between serum concentrations of sex steroids and BMI, and explored their predictive value for clinical response.
PATIENTS AND METHODS: Among the 116 post-menopausal patients enrolled in the JFMC 34–0601 clinical trial of 24 weeks (wks) of NAH with exemestane, serums from 60 patients at pre-treatment, at 4wks and end of the treatment (24wks) were subjected to this study. Estradiol (E2), estrone (E1), dehydroepiandrosterone (DHEA), androstenedione (A-dione), 5-androstene-3β, 17β-diol (Aenediol), 5α-androstane-3β, 17β-diol (Aanediol) were measured using LC-MS/MS analysis and E1- sulfate (E1S) was by RIA.
RESULTS: There were no significant correlations between pre-treatment concentrations of sex steroids and BMI, except for moderate correlation of E2 and BMI (p = 0.004). In multivariate analysis, E1 was an independent predictive factor for objective response [odds 6.0, 95% confidence interval (CI) 1.5 — 34.6, p = 0.011], as well as BMI. All of the estrogens decreased to under-detection levels (0.5 for E1 and E2, 5 pg/assay for E1S) at 4 wks of treatment, and maintained through to the end of treatment in almost all patients independently of clinical response. The geometric mean percentage changes in androgens after NAH were: DHEA −0.2% (95%CI −15.3% — +17.6%) for patients without progressive disease (non-PD) and +44.8% (95%CI +22.1% — +71.8%) for patients with progressive disease (PD); A-dione −2.3% (95%CI −17.3% — +15.4%) for non-PD and +45.6% (95%CI +28.3% — +65.3%) for PD; Aenediol −11.5% (95%CI −20.6% — −1.4%) for non-PD and +24.9% (95%CI +1.9% — +53.0%) for PD; Aanediol +21.3% (95%CI −5.5% — +55.8%) for non-PD and +56.3% (95%CI +5.3% — +132.0%) for PD, respectively. The changes in the concentrations of both DHEA and A-dione in patients with PD were statistically significant (p = 0.008 and p = 0.002, respectively). In all of the PD patients, the serum concentrations of DHEA and A-dione were increased after NAH.
CONCLUSION: Pretreatment serum concentration of E1 was an independent predictive factor for clinical response to NAH with exemestane. Measurement of dynamics of the serum androgen concentrations might be helpful for monitoring treatment response, and mechanism of increase of androgens has a value for further investigation. Our results should be validated using a larger dataset. (UMIN ID; C000000345)
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-18.
Abstract P3-06-25: PTEN mRNA positivity using in situ measurements is associated with better outcome in Tamoxifen treated breast cancer patients.
Authors: Schalper KA , Li K , Rimm DL 
Published: August 2014

Abstract
Background: Aberrant phosphatidylinositol 3-kinase (PI3K) pathway signaling occurs in a high proportion of human breast cancers and is involved in carcinogenesis, tumor progression and resistance to targeted therapies. Reduced levels of the tumor suppressor PTEN has been associated with PI3K pathway activation and is observed in ∼40% of breast carcinomas. PTEN levels have traditionally been determined in breast tumors by qualitative immunohistochemistry (IHC) and its prognostic and/or predictive value has not been clearly established. We used a novel method of quantitative in situ measurements of PTEN mRNA and protein to determine their possible prognostic and predictive value in breast cancer.
Materials and methods: PTEN mRNA and protein were measured on formalin fixed paraffin embedded (FFPE) cell lines and tumor samples on tissue microarrays (TMAs) representing a retrospective cohort of 404 breast cancer cases collected from the Yale Pathology archives between 1975 and 2005. The RNAscope paired-primer method was used for PTEN mRNA in situ hybridization (ISH), with Ubiquitin C and DapB ISH probes used as positive and negative controls for each run. PTEN protein measurements were performed with monoclonal antibody 138G6 (Cell Signaling Technology). Both mRNA and protein were measured using the AQUA method of quantitative immunofluorescence.
Results: Both PTEN mRNA ISH signal and protein were highly reproducible in FFPE tissues and cell lines. PTEN mRNA levels were lower in cell lines with known PTEN downregulation. In breast carcinoma samples, PTEN mRNA scores showed a positive non-linear association with protein levels. Neither PTEN mRNA nor protein showed prognostic value. However, high PTEN mRNA expression using a visually defined cutoff was associated with better outcome in a subset of Tamoxifen treated breast cancer patients.
Conclusion: Initial data suggests that PTEN mRNA expression may be predictive of favorable response to endocrine therapy in breast carcinomas. However, validation in larger independent cohorts is required.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-25.
Abstract P3-07-02: Time-trends in survival in young women with breast cancer in a SEER population-based study
Authors: Ademuyiwa FO , Groman A , Hong C-C , Kumar S , Levine EG , Miller A , Ambrosone CB 
Published: August 2014

Abstract
Background: As mammography is not generally recommended to women under 40, it is reasonable to conclude that documented outcome improvements over time are attributable to treatment advances with screening playing a less important role. In order to determine the contribution of screening and treatment to improvements, we evaluated the odds of presenting with more advanced disease by time-period and examined the time-trends in outcome in a population-based cohort ≤50. We evaluated whether any outcomes differentials existed by ER status.
Methods: Patients in SEER diagnosed with breast cancer (BC) were divided into 4 by year of diagnosis (1990–1994, 1995–1999, 2000–2004, 2005–2008). Patients were also categorized into 2 age-groups: &lt;40 and 40–50 years. Odds ratios for presenting with more advanced disease over the 4 time-periods were calculated for the 2 age-groups. Multivariate analysis was done to investigate the association of survival with time-period for the 2 age-groups by ER status.
Results: 110,629 patient records were included. Multivariate adjusted hazard ratio for mortality in women aged 40–50 with ER positive BC declined over time. Comparing all time periods to 1990–1994, the HR for mortality in 1995–1999 was 0.83 (0.77–0.89), 0.61 (0.57–0.65) in 2000–2004, and 0.35 (0.30–0.40) in 2005–2008 (p &lt;.001). Those &lt;40 years with ER positive BC also had mortality improvements over time (HR 0.86, 0.63, 0.26 for 1995–1999, 2000–2004, and 2005–2008 respectively). On the contrary, no mortality improvements were seen in women with ER negative disease. Trends in progressively worsening mortality over time were observed in this cohort.
A 1.3-fold increase in the odds of presenting with stage I BC was seen in women 40–50 years comparing the 3 latter time periods with 1990–1994. Similarly, in the same age group, there was a 2.12-fold likelihood of presenting with a tumor ≤1cm in 2005–2008 versus 1990–1994. In women &lt;40 years at diagnosis, the probability of presenting with stage I disease was lower in the 3 latter time periods than in 1990–1994; and a 2.84-fold higher probability of presenting with stage III/IV disease was seen in 2005–2008 compared with 1990–1994.
Conclusions: Patients who are ER positive and between 40–50 years have had time-trend changes with improvements in breast cancer outcome and smaller tumors likely attributable to both screening and hormonal therapies. Patients who are &lt;40 years and/or ER negative have not had improvements in breast cancer outcome.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-02.