bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing the Development of Breast Cancer by Immunizing with Multi-Antigen Vaccines Targeting Proteins Associated with Oncogenesis.
Authors: Disis M. , Cecil D. , Gad E. , Park K. , Lai V. , Lubet R. , Lu H. 
Published: December 2010

Abstract
Vaccines have been extremely successful in the prevention of infectious diseases. Although cancer vaccines have long been studied for the treatment of cancer, they have not been exploited as chemoprevention agents except in virally mediated malignancies. Human breast cancer is immunogenic and a variety of proteins involved in the malignant transformation or maintenance of the malignant phenotype have been identified as tumor antigens. Transgenic animal models are uniquely suited for evaluating the potential efficacy of preventative cancer vaccines. TgMMTV-neu mice, for example, develop neu-mediated breast cancer at about 150-200 days of life. Tumors are histologically similar to human breast cancer and have a molecular profile consistent with the luminal subtype. We have developed two multi-antigen vaccines targeting immunogenic proteins associated with oncogenesis and evaluated whether we could prevent the development of breast cancer in TgMMTV-neu mice. Each vaccine was composed of 3 different antigens. Class II epitopes derived from antigenic proteins involved in growth factor pathways comprised one vaccine and the other vaccine was plasmid DNA based and encoded immunogenic proteins involved in cell proliferation. The ability of active immunization to prevent breast cancer was evaluated in both older (18 week) and younger (5 week) mice. Vaccines were administered intradermally every two weeks for 3 immunizations and then monthly until the development of disease or 1 year had passed. Both vaccines prevented breast cancer development in older animals. 40% of peptide immunized older mice were cancer free at 1 year compared to 5% of controls (p=0.02). The DNA vaccine appeared to be even more effective in older animals with 60% of vaccinated mice tumor free as compared to 20% of controls (p=0.01). Protection from the development of cancer was mediated by T cells as evidenced by adoptive transfer of CD3+ cells purified from vaccinated and protected mice, sham immunized mice, and naïve mice. T cells from protected mice resulted in significant inhibition of tumor growth after a syngeneic tumor challenge (p=0.01 protected vs. sham vaccine). The cancer protective effect of immunization was more pronounced when vaccines were administered to the younger mice. The Class II epitope vaccine prevented cancer development in 65% of mice as compared to 5% of controls. The plasmid based vaccine protected 70% of mice from breast cancer. Active immunization was associated with a survival benefit in all groups. These data suggest breast cancer vaccines targeting biologically relevant proteins may be an effective approach to the prevention of breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1045.
Effect of Body Mass Index on Recurrence in Hormone Receptor Positive Early Breast Cancer – A Retrospective Exploratory Analysis from the ATAC Trial.
Authors: Sestak I. , Distler W. , Forbes J. , Howell A. , Cuzick J. 
Published: December 2010

Abstract
Background: Third generation aromatase inhibitors have been widely used in postmenopausal women for the adjuvant treatment of hormone receptor positive breast cancer. As aromatase inhibitors work by inhibiting the conversion of androgens to oestrogens in adipose tissue the effectiveness of aromatase inhibitors might be dependent on body mass index (BMI).Methods: The ATAC study was a double-blind randomised clinical trial in which postmenopausal women with early breast cancer were randomly assigned to receive oral daily anastrozole (1mg) alone, tamoxifen (20mg) alone, or the combination in a double blind fashion. In this retrospective investigation, analyses were based on those women with hormone receptor positive breast cancers (oestrogen (ER) and/or progesterone (PgR) positive) for whom a baseline BMI measurement was available (anastrozole=2469; tamoxifen=2470). Here, we investigate the influence of BMI on time to recurrence (TTR) and time to distant recurrence (TTDR), and also the relative benefit of anastrozole versus tamoxifen according to baseline BMI, using a proportional hazard model.Results: After 100 months of median follow-up, obese women (BMI&gt;30 kg/m2) at baseline had a significantly higher breast cancer recurrence rate than lean women (BMI&lt;23 kg/m2) (adjusted HR=1.27 (1.02-1.57), Ptrend= 0.003) (Table 1). Obese women also had 38% more distant recurrences compared to lean women (adjusted HR=1.38 (1.08-1.76), Ptrend &lt; 0.0001). The relative benefit of anastrozole versus tamoxifen was slightly greater in women with a low BMI but this was not significant for recurrence or distant recurrence (data not shown).Conclusions: These results confirm the poor prognosis of obese women with early breast cancer. Recurrence rates were lower in anastrozole than tamoxifen for all BMI quintiles and these results do not support an increased efficacy for anastrozole in obese women.Table 1: Number of breast cancer recurrences (% of group) and hazard ratios according to approximate BMI quintile for all recurrences and distant breast cancer recurrences. All breast cancer recurrences Distant recurrences Approx. BMI quintileNumber of events (%)HR* (95% CI) for TTRNumber of events (%)HR (95% CI)* for TTDR&lt;23 (N=966)134 (13.9)Reference97 (10.0)Reference23-25 (N=810)137 (16.9)1.14 (0.89-1.45)97 (12.0)1.11 (0.83-1.47)25-28 (N=1171)204 (17.4)1.22 (0.98-1.52)149 (12.7)1.21 (0.94-1.57)28-30 (N=643)117 (18.2)1.26 (0.98-1.62)86 (13.4)1.26 (1.08-1.69)&gt;30 (N=1582)253 (18.8)1.27 (1.02-1.57)203 (15.1)1.38 (1.08-1.76)P-trend 0.003 &lt;0.0001*HR adjusted for age, region, chemotherapy, radiotherapy, mastectomy, tumour size, tumour grade, nodal status
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1047.
Breast Cancer Prevention by Letrozole in Post Menopausal BRCA1/2 Mutations Carriers: The Onco-03/LIBER Trial.
Authors: Pujol P. , Mijonnet S. , Karen S. , Martin A. ,   on Behalf the French Genetic and Cancer Group
Published: December 2010

Abstract
Women carrying germline BRCA1/2 deleterious mutations are an extreme risk population for developing breast cancer, with a cumulative life-time risk of 56-80%. Prophylactic bilateral mastectomy provides a valid option for reducing the risk of breast cancer by nearly 90 %. Although it greatly affects the quality of life, breast prophylactic surgery in BRCA1/2 mutation carriers have increased in Europe and in US over the last decade.The major breast cancer prevention trials using tamoxifen and raloxifen showed an approximately 50% risk reduction in high risk women. The contralateral risk reduction in current adjuvant trials comparing aromatase inhibitors (AI) to tamoxifen therapies reveals a higher preventive efficacy of AI after menopause. Two ongoing randomized studies using exemestane (MAP3) or anastrozole (IBIS2) are assessing the risk reduction of breast cancer in menopausal women but none are designed for BRCA1/2 carriers.The French federation of cancer centres, "FNCLCC" (Federation Nationale des Centres de Lutte Contre le Cancer) has developed a randomized phase III study to determine the efficacy of the aromatase inhibitor letrozole to reduce the incidence of invasive breast cancer in post menopausal BRCA1/2 carriers. The ONCO-03 (LIBER) study is a double-blind, letrozole versus placebo, controlled study involving 28 centres in France. The study opened for recruitment in march 2008. The study design, procedures and first analysis of patients enrolment are presented.Based on the known preclinical and clinical profile of AI, a greater reduction in breast cancer incidence with fewer side effects is hypothesized with this class of agents than with tamoxifen or raloxifen. For postmenopausal women bearing a BRCA1/2 genetic predisposition, prevention of breast cancer risk by letrozole could provide a precious alternative to bilateral mastectomy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1048.
Return to Work after Treatment for Breast Cancer: Single Center Experience in a Cohort of 273 Patients.
Authors: Peugniez C. , Peugniez C. , Fantoni S. , Leroyer A. , Leroyer A. , Skrypczak J. , Duprey M. , Bonneterre J. , Bonneterre J. 
Published: December 2010

Abstract
Background: An increasing number of patients (pts) are treated for breast cancer during professional life. The aim of this study was to assess medical as well as socio-professional factors impacting on the likelihood of patients to return to work after treatment.Patients and methods: 1067 pts who were less than 60 years of age, and surgically treated in our institution between January 1, 2004 and December 31, 2005 received a questionnaire with medical, sociodemographic and professional items. An answer was obtained in 586 cases. After excluding in situ carcinoma, local relapses, bilateral tumors and pts without professional activity before treatment, 273 were evaluable. All the clinical files of these patients were reviewed. We studied return to work qualitatively (by univariate, then multivariate logistic regression) and quantitatively, by measuring time until return to work (by log-rank and then multivariate Cox model).Results: Overall, 79.8% of the patients returned to work after a median delay of 11.5 months. In the multivariate analysis, the factors affecting the return to work were: age (p&lt;.0001), particularly pts &gt;55 years returning to work in 58% of cases vs more than 80% in younger ones, education level (p&lt;.001), colleagues support (p&lt;.001), chemotherapy (p&lt;.05), lymphedema (p&lt;.01), and the physical (p=.01) and psychological constraints of the job (p&lt;.01). Surprisingly, local pain with ankylosis of the shoulder was significant only in the univariate analysis (p&lt;.0001). In the multivariate analysis, the factors affecting the delay between treatment and return to work were very similar: age (p&lt;.01), education level (p&lt;.0001), colleagues support (p&lt;.0001), chemotherapy (p&lt;0001), lymphedema (p&lt;.01), and the professional constraints of the job (p&lt;.0001). No significant difference was observed according to type of surgery, tumorectomy vs mastectomy, sentinel lymph node vs axillary clearance, radiation therapy or not, hormonotherapy or not.Conclusion: in our study, 80% of the pts with a professional activity before treatment returned to work; the factors affecting the return to work as well as its delay were: medical (chemotherapy and lymphedema), demographic (age) and socioprofessional (education level, which induces differences in the socio-professional groups, constraints of the job, colleagues support). We could not find any influence of the other treatments such as radiotherapy or hormonotherapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1060.
Prevalence and Risk Factors for Insomnia in Breast Cancer Survivors Receiving Aromatase Inhibitors.
Authors: Mao J. , Gehrman P. , Su I. , Bruner D. , Xie S. , El Sehamy A. , DeMichele A. 
Published: December 2010

Abstract
Purpose: Insomnia is increasingly recognized as a major symptom outcome in oncology; however, its prevalence and risk factors have not been previously defined in women receiving aromatase inhibitors (AI) for breast cancer.Patients and Methods: We performed a cross-sectional analysis of a cohort of postmenopausal women with stage 0-III breast cancer receiving adjuvant AI therapy at an outpatient breast oncology clinic at a large university hospital. The validated Insomnia Severity Index (ISI) was the primary outcome (Cronbach's alpha of 0.91 in this population). According to ISI, Insomnia was categorized as: no clinically significant insomnia, 0-7; sub-threshold insomnia 8-14; clinical insomnia (moderate severity), 15-12; clinical insomnia (severe), 22-28. We defined anyone who had clinical insomnia with a score of 15 or above. Multivariate logistic regression analyses were performed to assess risk factor(s).Results: 367 patients have been analyzed, with a mean age of 61.6 +/- 10 years. 83.6% were White and 12.9% Black. While 124 (34.1%) had sub-threshold insomnia, 67 (18.4%) met criteria for clinical insomnia based on ISI: 58 (15.9%) for clinically moderate insomnia and 9 (2.5%) clinically severe insomnia. Of the entire sample, 31% considered seeking treatment for insomnia over the previous month. In a multivariate logistic regression model, clinical insomnia was independently associated with current joint pain (odds ratio [OR], 4.41, 95% confidence interval [CI], 2.17-8.96, p&lt;0.001) and hot flashes (OR, 3.00, 95% CI, 1.58-5.71, p=0.001). While education level (college only vs. graduate or professional degree) was also associated with increased risk for clinical insomnia (OR, 2.46, 95% CI, 1.18-5.14, p=0.016), no other demographic, clinical or treatment variable was related to clinical insomnia.Conclusions: Insomnia is a substantial problem among breast cancer survivors receiving aromatase inhibitors and is highly associated with joint pain and hot flashes. Thus, effective treatment of joint pain and hot flashes may help improve insomnia in this population.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1062.
Psychosocial Interaction from the Patients Point of View – Patient Satisfaction by CPQ-BC (Cologne Patient Questionnaire – Breast Cancer) in 51 German Breast Centers.
Authors: Wuerstlein R. , Steffen P. , Kowalski C. , Alich M. , Warm M. , Pfaff H. , Harbeck N. 
Published: December 2010

Abstract
Background: The implementation of breast centers aims at improving the quality of care for breast cancer patients. Hereby the quality of psychosocial interaction from doctors and nursing staff is an essential aspect for patient satisfaction. This presentation based on empirical data shows the quality of psychosocial interaction from the point of view of patients in 51 german breast centers and if it has changed in annual comparison. Moreover, it analyses how the individual breast centers differ from each other and gives benchmarking data as well as data concerning the increasing significance attributed by patients to the assessment of quality of care and patient satisfaction.Material and Methods: Basis for the data is a retrospective survey of 10837 newly diagnosed breast cancer patients after primary surgery between 2006 and 2008 in 51 breast centers in Germany. After being inpatients, they were sent the specially developed Cologne Patient Questionnaire for Breast Cancer (CPQ-BC) which comprises key data to relevant aspects of psychosocial interaction such as support from physicians or nursing staff, doctor facilitation scale, patient information scale, patient participation in decision making, empathic provision of information, provision of information by physicians (basic and additional information), physical functioning, psychological well-being and tendency to excuse.Results: 88% of the contacted patients returned a completed questionnaire. The results of the descriptive analyses show that the quality of psychosocial interaction in the breast centers was overall evaluated very positively and that it is relatively stable in three years time. However, there are clear differences between the individual centers.Discussion: We noted that the quality of psychosocial interaction in the german breast centers already has a high standard from the patients point of view. This standard needs to be maintained and developed further. Moreover, the declared aim should be to dismantle the existing differences in quality between the centers. A specific evaluation of various structure and process features can give information on the reasons for these differences. Benchmarking data and specially developed benchmarking workshops help breast centers and their teams to improve quality of care and provide a good psychosocially supportive provider-patient interaction.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1071.
Medical Oncology Breast Cancer Quality Indicators: Adherence by the Florida Initiative for Quality Cancer Care (FIQCC) Consortium.
Authors: Gray J. , Laronga C. , Siegel E. , Lee J. , Fulp W. , Jacobson P. 
Published: December 2010

Abstract
Background: The Florida Initiative for Quality Cancer Care (FIQCC) is comprised of 11 practice sites across the state that participate in a comprehensive review of quality of care specific to cancer patients across many disease sites. Quality indicators were scripted based on accepted QOPI, NCCN, ACOS, and site-specific PI panel consensus indicators for breast cancer (BRCA) patients. An evaluation was performed to assess adherence to the performance indicators across sites within the FIQCC.Methods: Comprehensive chart reviews were conducted for all patients with BRCA first seen in 2006 by a medical oncologist at one of the 11 FIQCC sites (3 academic/8 community). Quality measures included: 1) documentation of menopausal status; 2) documentation of receptor status in the chart and evidence that it guided treatment recommendations accordingly; 3) documentation that consent for chemotherapy was obtained; 4) documentation of the planned chemotherapy regimen; and 5) documentation that chemotherapy started within 8 weeks of surgery. A pilot measure included: 6) documentation of fertility preservation being addressed in pre-menopausal women. Pearson's Chi-square test was used to test variability on the quality measurements across practice sites.Results: Charts of 622 patients (99% female), median age of 60 years (range 22-95) were reviewed. Menopausal status was documented in 49% (307/622). Documentation of the receptor status (ER/PR/ Her2Neu) was excellent, 99% (532/537). For those with ER/PR positive, non-metastatic disease measuring at least 1cm, 98% (432/441) were considered for an aromatase inhibitor or tamoxifen within one year of diagnosis. For patients with Stage II-III BRCA with over-expression of Her2Neu (H2N), consideration or administration of trastuzumab was documented in 82% (95/116). With respect to chemotherapy, there was documentation of consent in 75% (247/330), planned chemotherapy regimen in 75% (226/302), and initiation of chemotherapy with 8 weeks of surgery in 84% (233/279). Fertility preservation was only addressed in 11% (10/88) of patients who were documented as pre-menopausal. A statistically significant difference (p&lt; 0.05) across the sites was found for all quality indicators above, except two: documentation of consideration or administration of trastuzumab and discussions of fertility preservation.Discussion: The FIQCC allows for the identification of the need for quality improvements in multiple aspects of breast cancer care. Findings based on 2006 cases identified need for improvements in documentation and consenting for chemotherapy, reporting of menopausal status, consideration and administration of trastuzumab, and consideration of fertility counseling. These findings are now being used at the participating institutions to guide quality improvement efforts.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1078.
Breast Cancer Stem Cells Identified by ALDH1 Expression Were Associated with Resistance to Sequential Paclitaxel and Epirubicin-Based Chemotherapy for Human Breast Cancers.
Authors: Tanei T. 
Published: December 2010

Abstract
Background: Breast cancer stem cells have been demonstrated to be associated with resistance to chemotherapy in vitro, but their clinical significance has yet to be examined in human breast cancers. The aim of this study was to investigate whether breast cancer stem cells were clinically associated with chemo-resistance or not.Material and Methods: The subjects recruited for this study comprised 108 primary invasive breast cancer patients treated with neoadjuvant chemotherapy (NAC) consisting of sequential paclitaxel and epirubicin-based chemotherapy. Cancer stem cells were identified by immunohistochemical staining of CD44/CD24 or ALDH1 in tumor tissues obtained before and after NAC.Results: The pathological complete response (pCR) was achieved in 30 patients (27.8%) of the 108 patients treated with NAC. ALDH1 positive tumors were significantly associated with a low pCR rate (9.5% vs. 32.2%; P = 0.037), but there was no significant association between CD44+/CD24- tumor cell proportions and pCR rates. Changes in the proportion of CD44+/CD24- tumor cells or ALDH1 positive tumor cells before and after NAC were examined in 78 patients who did not achieve pCR. The proportion of ALDH1 positive tumor cells significantly increased (p&lt;0.001) after NAC, but no significant change was observed in the proportion of CD44+/CD24- tumor cells before and after NAC. In addition, we were able to show, by multivariate analysis, that tumors with negative ER, high Ki67, and negative ALDH1 were significantly more likely to achieve pCR.Discussion: Our findings suggest that breast cancer stem cells identified as ALDH1 positive, but not CD44+/CD24-, play a significant role in resistance to chemotherapy. ALDH1 positive tumor cells are likely to serve as a better marker for breast cancer stem cells than CD44+/CD24- tumor cells for the prediction of resistance to chemotherapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1084.
Effectiveness of Neoadjuvant Letrozole of Invasive Lobular Cancers.
Authors: Dixon J. , Renshaw L. , Evans D. , Thomas J. 
Published: December 2010

Abstract
Background:Invasive lobular cancers are poorly responsive to neoadjuvant chemotherapy. They are commonly hormone sensitive. This study set out to investigate the efficacy of neoadjuvant letrozole in post-menopausal women with large operable or locally advanced breast cancers.Patients and Methods:48 consecutive patients with large operable or locally advanced invasive lobular ER positive (Allred score 8 = 38, 7 =8, 6=1, 5=1) were treated in a single Breast Unit by neoadjuvant letrozole for 3 months or longer. The mean age was 76.7 years with a range of 55 to 91 years. 6 tumours measured &gt;2-4 cm (T2), 26 tumours measured &gt;4 cm (T2, T3) and 16 were locally advanced (T4). Response was assessed by a single observer at 3 months.Results:Response to TreatmentThe mean reduction in clinical volume at 3 months was 60% (95% CI 50-79%) with a median of 67% (95% CI 60-79%). Responses were classified as 1 Complete Response (CR), 25 Partial Response (PR), 16 Minimal Response (MR), 4 Stable Disease (SD) and 2 Progression.The mean USS in volume was 69% (60-78%), with a median of median 80% (66-84%). Response was classified as CR= 12, PR = 25, MR = 7, SD = 3 and Progression = 1.Surgery and Outcome32 have come to surgery and 16 have continued on letrozole.24 patients were considered suitable for breast conserving surgery (WLE) of whom 16 successful had WLE (67% with Clear Margins), 4 had a WLE and then a successful re- excision of margins and 4 had a WLE followed by mastectomy. The final rate of successful breast conservation was thus 20/24 (83%).8 patients with locally advanced breast cancer became operable and were treated by mastectomy.SummaryThis is the largest series of invasive lobular carcinomas treated by neoadjuvant letrozole ever reported.Invasive lobular carcinomas are often large at diagnosis.They are mainly ER rich.In post-menopausal women they respond well to endocrine therapy with letrozole.Neoadjuvant therapy with letrozole allows many women with large invasive lobular carcinomas to be treated successfully with breast conservation.This contrasts with the poor results obtained with neoadjuvant chemotherapy.ConclusionNeoadjuvant letrozole therapy is an effective treatment for shrinking invasive lobular ER positive breast cancers in post-menopausal women.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1085.