bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-11-05: Association between Bisphosphonate Use in Metastatic Breast Cancer (MBC) and Overall Survival.
Authors: Mathew A , Mathew IE , Rosenzweig MQ , Brufsky AM 
Published: June 2012

Abstract
Background
Pre-clinical studies on bisphosphonates in breast cancer have suggested an anti-tumor effect in addition to its bone protective role. However, randomized controlled trials of bisphosphonates versus placebo have found little evidence of increased overall survival (OS) in MBC. We conducted a retrospective single institution cohort study of MBC patients to evaluate the association between bisphosphonate use and overall survival.
Methods: Baseline demographic and tumor specific data were collected on newly diagnosed MBC patients between January 1998 and December 2009. Other variables included the number and sites of each metastasis, use of baseline neoadjuvant and adjuvant chemotherapy, and use of hormonal therapy. Bisphosphonate use was defined as present if it was administered for a period of at least 3 months in the metastatic setting. Overall survival was determined from the date of diagnosis of first metastatic disease. Survival analysis was performed using the Kaplan-Meier method and Cox proportional-hazards model.
Results: Data were available on 737 patients with MBC, of whom 434 died during a median follow-up of 2 years; median age was 50.3 years. 92% of patients were Caucasian; 32% were both ER and PR-negative; and 31% were HER2−positive. Over 67% of MBC patients had bone metastasis and nearly 80% received bisphosphonates. Multivariate analysis found an overall survival benefit for bisphosphonate use, with a hazard ratio of 0.63 (95% confidence interval: 0.48−0.84; p&lt;0.002), when adjusted for variables with significant effect on survival on univariate analysis and other known prognostic variables. These variables include age, stage at diagnosis, race, hormone receptor status, HER2 status, and number of metastatic sites, presence of bone metastasis and the use of adjuvant therapy. The administration of adjuvant therapy did not yield a significant survival advantage in the analyses.
Conclusion: This retrospective cohort study provides evidence for an OS benefit with the use of bisphosphonates in MBC even after controlling for other significant prognostic factors.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-05.
P4-11-07: Feasibility and Acceptability of Offering Breast Cancer Risk Estimation in the Context of the UK National Health Service Breast Cancer Screening Programme: A New Paradigm for Cancer Prevention.
Authors: Evans DGR , Astley S , Stavrinos P , Sahin S , Ingham S , McBurney H , Eckersley B , Wilson M , Beetles U , Harvie M , Warren R , Sergeant J , Hufton A , Warwick J , Newman W , Buchan I , Cuzick J , Howell A 
Published: June 2012

Abstract
Background: Currently there are no real attempts internationally to tailor breast screening programmes to individual risk Methods: We have assessed the feasibility of collecting breast cancer risk information during routine mammographic screening in the National Health Service Breast Screening Programme (NHSBSP) in England, in order to consider, ultimately, adapting the screening interval to risk of breast cancer and introducing preventive strategies in women at high risk. The study Predicting Risk Of Cancer At Screening (PROCAS) aims to recruit 60,000 women over 3 years. Results: 26,000 women (June 8th 2011) have so far given consent to join the study. Thirty six percent of the first 20,000 women in nineteen screening sites in Manchester consented to enter the study and completed a risk factor questionnaire. The median 10 year breast cancer risk was 2.65%, with 926 (9.26%) of the first 10,000 women having a 10 year risk of ≥5% and 92 (0.92%) having a 10 year risk of ≥8% (Tyrer-Cuzick), IQR:1.35. 832 (8.32%) women had a mammographic density of 60% or greater (Visual Analogue Scale). We collected saliva samples from 1019 women for genetic analysis and will extend this to 18% of participants. Of those who agreed to participate in the study, 94% indicated that they wished to know their breast cancer risk. Women with a 10-year risk of ≥8%, and women with a 10-year risk of ≥5% and mammographic density ≥60% were invited to attend or be telephoned to be counselled. To date 138 have accepted with 135, so far, having received risk counselling. Nineteen percent of the high-risk women identified subsequently decided to enter a randomised breast cancer prevention study with either a dietary or drug intervention (IBIS2, anastrazole vs placebo). Results from the first 1,000 women who provided DNA samples suggest that the risk information from the 18 validated SNPS may enhance existing risk models. Conclusion: This study demonstrates that it is feasible to determine individual breast cancer risk and offer women appropriate risk-reducing interventions within the context of a population-based mammographic screening programme.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-07.
P4-11-08: Changes in the Distribution of Loco-Regional and Distant Breast Cancer Recurrences over the Last 20 Years: Implications for Patient Care and Future Research.
Authors: Bouganim N , Clemons M , Amir E 
Published: June 2012

Abstract
Introduction: Improvements in adjuvant therapy have led to a sustained fall in recurrences after early breast cancer. The differential reduction of both local-regional and systemic recurrences is poorly understood. This study aimed to explore changes in the distribution of loco-regional and distant recurrences in clinical trials reported over the last 20 years. We also aimed to determine the relative impact of adjuvant chemotherapy and endocrine therapy.
Methods: A MEDLINE search for adjuvant, Phase III randomized breast cancer clinical studies between January 1990 and March 2011 was performed. Neo-adjuvant, single agent biologics and studies that did not report the proportion of loco-regional and distant recurrences were excluded. Change in the frequency of recurrences was assessed as the non-parametric correlation between the number of loco-regional recurrences (as a proportion of all recurrences) and time. Studies were weighted by sample size. Pre-specified subgroup analyses were assessed using the interaction test and included type of surgery performed, radiotherapy use, menopausal status and type of systemic therapy delivered. Definition of local and distant recurrences differed between studies. For consistency, loco-regional recurrences were classified as recurrences limited to the ipsilateral breast, chest wall, axillary, supraclavicular and internal mammary lymph nodes. Any other recurrence was defined as distant, with the exception of contralateral breast cancer; that was excluded from this analysis.
Results: Fifty-three randomized clinical trials with a total of 86,598 patients were included in the analysis. Between 1990 and 2011, the proportion of loco-regional recurrences has decreased from approximately 50% to 10% (Spearman's rho = −0.40, p&lt;.001). There was no interaction between type of surgery (mastectomy vs. lumpectomy, p=0.40), adjuvant radiotherapy use (p=0.63) and menopausal status (p=0.95) and the correlation of loco-regional recurrences and time. Chemotherapy use showed a larger negative correlation compared with endocrine therapy (rho = 0.49 vs rho = 0.24, p=0.008).
Conclusion: Advances in treatment of early breast cancer have differentially reduced the proportion of loco-regional recurrences compared with distant recurrences. In recent trials, loco-regional recurrences account for less than 10–15% of all recurrences. These falling event rates may affect patient care, especially when deciding on treatments influencing loco-regional control. This change may also impact on the design of clinical trials assessing loco-regional therapy such as surgery and/or local radiation therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-08.
P4-11-12: Molecular Phenotype of Breast Cancers in a Large Cohort of Young Women According to Time Interval Since Pregnancy.
Authors: Collins LC , Gelber S , Marotti JD , Cole K , Kereakoglow S , Ruddy KJ , Brachtel EF , Schapira L , Come SE , Borges VF , Schedin PJ , Warner E , Winer E , Partridge A 
Published: June 2012

Abstract
Background: The increase in breast cancer risk during pregnancy and post partum is well recognized. The cross-over to protective effect does not occur until many years later and varies with age at first birth. Recently, a genomic signature specific to the pregnant compared with the non-pregnant breast has been identified; this signature remains present in the postmenopausal parous breast. Given this, we investigated whether time interval since pregnancy affects the phenotype of breast cancers arising in young women compared with nulliparous women. Methods: We examined molecular phenotype, according to histologic grade and biomarker status, in relation to time since pregnancy in an ongoing prospective cohort study (n=355) of young women (≤40yrs) with breast cancer. Medical records were reviewed for tumor stage and receptor status. Parity was ascertained from questionnaires completed within 9 months of diagnosis. Tumor grade was determined by central pathology review. Using tumor grade and biomarker expression, cancers were categorized as luminal A (ER+ and/or PR+, HER2−, histologic grade 1 or 2); luminal B ( ER+ and/or PR+, HER2+, or ER and/or PR+, HER2− and grade 3); HER2 type (ER-, PR-, HER2+); and triple negative (ER-, PR-, HER2−).
Results: The median age of the study population is 37 years (range 17–40). Overall, 80% of women had stage 1 or 2 disease; 67% of cancers were ER positive and 32% showed HER2 overexpression. The distribution of breast cancer molecular phenotypes by time interval since last pregnancy is shown in the table.
Distribution of molecular phenotype by interval between last pregnancy and diagnosis

In our large cohort of parous young women, we found no differences in the distribution of molecular phenotype according to time interval since pregnancy. However, nulliparous young women were more likely to develop luminal A cancers compared to parous women (40% vs. 29%; unadjusted chi square p-value=0.03) and appeared less likely to develop HER2−type and triple negative cancers (7% vs. 13%, p-value=0.09 and 17% vs. 23%, p-value=0.22 respectively). There were no differences in the distribution of luminal B cancers. Conclusions: The distribution of molecular phenotypes is similar among parous young women regardless of the time interval since parturition. Nulliparous young women appear more likely to develop luminal A cancers compared to parous women. Whether the difference in molecular phenotypes of pregnancy-associated breast cancers vs. cancers arising in nulliparous women is due to the effects of genomic alteration remains to be investigated. Effects of a prior pregnancy appear consistent across a 5-year period, in keeping with the concept of genomic alterations identified in the normal pregnant breast and thereafter.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-12.
P4-12-15: Cancer Survivor Care: An Evaluation of a Group Visit Model of Care for Breast Cancer Survivors at Duke Cancer Center.
Authors: Trotter KJ , Schneider S 
Published: June 2012

Abstract
Background: The number of cancer survivors is growing, currently with about 2.5 million breast cancer survivors. (ACS, 2010). The Institute of Medicine report on survivor care stressed care coordination along with attention to survivor concerns as key issues in improving follow-up care. Group visits have been shown to improve access, health outcomes and health care utilization rates, as well as self-management skills.
Purpose: This prospective program evaluation measured patients opinions about participation in a group visit clinic.
Methods: A new model of breast cancer survivor care was designed and piloted at Duke Cancer Center. Breast cancer survivors who were three years post diagnosis attended the clinic together in groups of six. An interdisciplinary group visit format in the initial part of the appointment provided surveillance, education and support, as well as formation of an individualized survivorship care plan to be shared with the primary care provider. The first hour included review of their personal care plan and a 45-minute facilitated discussion. Afterwards, individual visits with the nurse practitioner, and dietitian, physical therapist or social worker occurred.
A 22-item questionnaire designed to ascertain opinions regarding logistics and the style and function of care delivered is being administered to participants. The evaluation tool was approved by a panel of experts; pilot tested and has a reading level of 7.8. Data collection will be complete July 1, 2011. 103 surveys have been collected with a 91% response rate. Preliminary analysis shows high satisfaction with the group visit format. What participants liked most about the program was sharing with other survivors. 86% of participants indicate that they will share the survivorship care plan with their PCP. Only 10% responded that they were not sure they needed this type of follow up now and expressed that it would be more helpful immediately after finishing treatment. Final data will be presented. Barriers and facilitators to implementing this type of care model will be presented.
Conclusions: The group visit model applied to a breast cancer survivor clinic appears feasible and highly satisfactory to participants. Implications for practice: Group visits can be considered one option for survivor care.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-15.
P4-16-03: Proof of the Anti-Tumour Effect of Zoledronic Acid (ZA) in Naive Bone-Only Metastatic and Locally Advanced Breast Cancer: Results from the Biological Window Therapy.
Authors: Foroni C , Andreis D , Maldotti M , Cappelletti MR , Generali DG 
Published: June 2012

Abstract
Background: Pre-clinical studies have demonstrated an anti-tumour activity of ZA in several cancers. However, the clinical evidence of the ZA anti-tumour effect is still uncertain. Our study aimed to prove that ZA has anti-tumour activity administered alone as a biological window of 14 days therapy on naïve bone-only metastatic and locally advanced breast cancer.
Material and Methods: 27 patients with locally advanced breast cancer (Group 1) and 12 patients at their first relapse with bone metastasis only (Group 2) received 4 mg single dose of ZA before starting with any treatment. In Group 1, Ki67 expression was evaluated in tumour specimens obtained before and after ZA administration (basal, day 14). In Group 2, circulating tumour cells (CTCs) were evaluated at baseline, 48 hrs and day 14. In Group 1 and 2, the apoptosis and necrosis of tumour cells were tested on blood samples by M30 and M65 ELISA assay respectively. Parallel, the anti-antitumor activity of ZA, given at the dose of 250 mg/mouse every 4 days for 6 cycles, in MDA-Mb-231 bearing mice was evaluated.
Results: A significant reduction of Ki67 expression after 14 days (mean, 25.33% to 21.78%; p=0.035) was observed in Group 1. In Group 2, we detected a significant reduction of CTC number after 48 hrs (median, 16 to 7; p=0.045), followed by a tendency to increase on day 14 (p=0.093). The M30/M65 analysis performed on paired blood samples in Group 2 showed after 14 days a significant increase in M65 (median, 97 to 112 U/L; p=0.018), more accentuated than the concomitant increase in M30 (p=0.308). In MDA-MB-231 bearing mice, ZA treatment caused a significant inhibition of tumor growth.
Conclusions: These results are the first prospective clinical data showing a direct anti-tumour effect (either on the tumour or on CTCs) of ZA, confirming the in vitro data. By directly affecting the proliferation, ZA could have an anti-tumour effect via induction of necrosis, suggesting its possible use in combination with conventional oncologic treatments of breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-03.
P4-17-03: Incidence Rate of Asymptomatic Brain Metastases in Patients with HER2+ Metastatic Breast Cancer Screened for EGF111438/CEREBEL Study.
Authors: Pivot X , Hackmann J , Manikhas A , Moore Y , Parikh R , Kothari D , Joshi A , Aktan G , Coleman R 
Published: June 2012

Abstract
BACKGROUND Brain metastases constitute a major clinical concern occurring in 28–43% of women treated for HER2+ metastatic breast cancer (MBC). The initial diagnosis of Central Nervous System (CNS) lesion is commonly based upon development of neurological symptoms. Data to address incidence of CNS lesions in asymptomatic patients are rare and not generally reported. EGF111438/CEREBEL study requires systematic screening for brain metastases by brain MRI and the ineligible patients due to detection of asymptomatic brain metastases are reported here.
METHODS The patients screened for CEREBEL have consented to a multi-centre, open-label Phase III study in subjects with HER2+ metastatic breast cancer who received prior treatment with anthracyclines or taxanes and trastuzumab in the adjuvant or metastatic setting. Eligible subjects must not have any history of CNS metastases (including leptomeningeal involvement) or have evidence of benign or malignant brain tumours and/or clinical evidence of spinal cord metastases at baseline. In order to confirm this, subjects must have negative brain MRI at baseline as confirmed by independent review (IR). All MRI scans of the brain had to be acquired with gadolinium contrast agent (T1 only) and 3mm slice thickness without gaps. The primary endpoint of CEREBEL is the incidence of CNS lesions as first site of relapse. A total of 650 subjects (325 per group) are expected to be randomized between capecitabine + trastuzumab versus capecitabine + lapatinib.
RESULTS The study is currently recruiting with 322 patients enrolled as of 15.06.2011. At this date, the total number of patients screened were 492 and 170 of these patients were screen failures. There are 15 patients in screening. The percentage of screen failures due to asymptomatic brain metastases assessed by investigators was 13.5% (23/170). The overall incidence of clinically asymptomatic brain metastases assessed by investigators for this study is 4.7% (23/492).
CONCLUSIONS Around 5% of all screened patients (14% of screen failures) in this study who were clinically thought to be free of brain lesions actually had brain metastases verified by brain MRI. We therefore conclude that screening for occult brain metastases by MRI is important for trials with defined CNS endpoints.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-03.
P4-18-01: Prognostic Role of Tumor and Stromal p16/INK4A in Ductal Carcinoma In Situ (DCIS).
Authors: Linke SP , Bremer TM , Wärnberg F , Zhou W , Goldstein L , Jirström K , Amini R-M 
Published: June 2012

Abstract
Background
DCIS is a pre-invasive breast disease diagnosed in ∼50,000 women/year in the US. The standard treatment recommendation is for mastectomy or breast-conserving surgery plus radiotherapy (BCS+RT). However, only ∼10% of BCS patients avoid recurrence due to RT, and RT provides little or no survival benefit. Thus, it is important to stratify patients by risk to help tailor treatment to maximize benefit and minimize unnecessary adverse effects and costs.
Material and Methods: Tissue microarrays that included tumor cores from all women diagnosed with pure DCIS between 1986 and 2004 in Uppland and Västmanland, Sweden (n=458) were stained and scored for p16/INK4A (clone E6H4) using immunohistochemistry (IHC). Semi-quantitative manual scoring was done separately in the tumor epithelial cells and peri-tumoral carcinoma-associated fibroblasts (CAFs). Based on previous reports, thresholds to define low and high p16 levels were set at 25% and 5% positive staining, respectively, for the tumor and stromal components. HER2 IHC scoring was reported previously. Clinicopathologic characteristics of the set of patients for which complete marker data was obtained (n=176) were not statistically different than the full set of patients. For survival analysis, local ipsilateral DCIS and invasive recurrences, as well as lymph node and distant metastases, were included as events (patients were censored if they had contralateral breast or other cancers as the first event).
Results: Patients were stratified into low and high risk groups using a multivariate model incorporating tumor p16, stromal p16, HER2, and margin status. Patients treated with BCS only (n=67) had a baseline 10-year recurrence rate of 31%. The model identified high and low risk groups with 10-year recurrence rates of 38% and 7%, respectively (hazard ratio=7.1, p=0.009). Similar results were achieved when BCS only and BCS+RT patients were combined (n=130). Interestingly, all six recurrence events in the set of patients who received full mastectomies (n=43) were in the model high risk group.
Discussion: Previous studies have shown mixed results when p16 was used as a single marker. Our results suggest a prognostic interaction between tumor and stromal p16, as well as HER2, that will form the basis of a more comprehensive multi-marker IHC-based prognostic panel to assess risk of recurrence in DCIS patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-18-01.
P5-01-16: The Detection of Circulating CK19 mRNA-Positive Cells in the Blood and the Mitotic Index of the Primary Tumor Have Independent Prognostic Value in Early Breast Cancer.
Authors: Tryfonidis K , Perraki M , Apostolaki S , Kafousi M , Agelaki S , Georgoulias V , Stathopoulos EN , Mavroudis D 
Published: June 2012

Abstract
Background: Previous studies have shown that the molecular detection of CK-19 mRNA in peripheral blood and the mitotic index of primary tumor have prognostic value in early breast cancer. The aim of the present study was to assess the association between these variables. Patients and Methods: The primary tumors of 223 operable breast cancer patients (92 premenopausal and 131 postmenopausal) were evaluated for the mitotic activity index (MAI) classified either as &lt;5/10, 6–10/10 and &gt;10/10 or &lt;10/10 and &gt;10/10 mitoses/hpf using a standardized protocol as previously reported (Baak JP et al, Breast Cancer Res Treat 2009, 115:241–254). Peripheral blood was also collected before the start and after the end of adjuvant chemotherapy for detection of CK-19 mRNA-positive cells by RT-PCR as previously described (Stathopoulou et al, Clin Cancer Res 2003, 9:5145–5151). Results: After a median follow-up of 118 months, 75 (33.6%) patients have experienced disease relapse and 56 (25.1%) have died of breast cancer. MAI was strongly associated with disease-free survival (DFS) and overall survival (OS) (p&lt;0.001 for both DFS and OS). Detection of CK19 mRNA-positive cells in the peripheral blood before but not after adjuvant chemotherapy was marginally associated with worse DFS (p=0.055) and OS (p=0.059). There was no correlation between MAI and CK19 mRNA detection before chemotherapy. Cox regression analysis revealed that both MAI and CK19 mRNA-positive cell detection before adjuvant chemotherapy were independent variables associated with decreased DFS (p&lt;0.001 and p=0.038, respectively) and OS (p&lt;0.001 and p=0.029, respectively). The interaction test showed no significant association between MAI and detection of CK19 mRNA-positive cells.
Conclusion: MAI of the primary tumor and detection CK-19 mRNA-positive cells in the blood before the start of adjuvant chemotherapy in women with early breast cancer are two independent prognostic factors associated with clinical outcome.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-16.