bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-02-02: The Natural Fetal Estrogen Estetrol (E4), Causes Anti-Estrogenic Effects in Women with Endocrine-Responsive Positive Early Breast Cancer.
Authors: Singer CF , Natter C , Steurer S , Rudas M , Moinfar F , Appels NRCA , Visser M , Kubista E , Bennink C 
Published: June 2012

Abstract
Background: Estetrol (E4) is a natural fetal estrogen which exerts estrogenic effects on reproductive organs and on the bone, and effectively reduces menopausal smyptoms. In contrast to other estrogens, however, E4 has estrogen-antagonistic effects on breast cancer cell lines in vitro and in the rat DMBA model, which would make it a suitable Hormone Replacement Therapy (HRT) in breast cancer patients, particularly in women who are being treated with aromatase inhibitors.
Patients and Methods: We have investigated the effect of 14 days preoperative treatment with 20 mg E4 per day on tumor proliferation, apoptosis, ER-receptors, PgR receptor and several endocrine parameters in a prospective, randomised, double-blind, placebo-controlled, neo-adjuvant study in 15 pre- and 14 postmenopausal women with estrogen-receptor positive early breast cancer. Results: Estetrol induced a significant increase of SHBG, a significant decrease of FSH in postmenopausal women and no increase of gonadotrophins in premenopausal women. Estetrol had no effect on Ki67 expression and on apoptosis-related Bax and Bcl-2, but the apoptosis index in tumor tissue increased significantly. Systemic IGF-1 levels decreased significantly. Surprisingly the intratumoral epithelial ER-alpha expression decreased significantly, whereas the ER-beta expression showed a trend to increase.
Conclusion: Our data suggest that E4 may be suitable and safe for HRT in women with spontaneous or induced menopausal symptoms, since apoptosis increases, IGF-1 decreases and no unfavourable effects are observed on Ki67, Bax and Bcl-2. The decrease of ER-alpha and the increase of ER-beta suggest a mechanism of action, explaining why the natural fetal estrogen E4 has estrogen-antagonistic effects on breast cancer tissue.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-02.
P4-07-12: Identification of p53 Mutation in Whole Genome DNA from Single Circulating Tumor Cells (CTCs) and Primary Breast Cancers (BC) from Patients (pts) with Metastatic Breast Cancer (MBC).
Authors: Yang L , Wang Y , Chu P , Liu Q , Hsieh B , Liu X , Yen Y , Bruce R , Somlo G 
Published: June 2012

Abstract
Background: CTCs represent the source of distant metastases, and are also implied in the growth/re-growth of primary BC. Molecular/gene-level characterization of similarities and discordances between CTCs and BCs in pts with MBC may provide useful information for individualized treatment. Since somatic p53 mutations are frequently observed in primary BCs, we set out to assess the feasibility of identifying such mutations in CTCs from pts with MBCs, and compare the findings with those of the primary BCs from the same pts. Material and Method: Fiber-optic Array Scanning Technology (FAST) was used for identification and location of CTCs on large glass substrates. CTCs were identified after blood samples (10 ml) from MBC pts were stained to detect CTCs via automated digital microscopy by morphology, based on immunofuorescence staining for cytokeratin and nucleus, and the absence of CD45. Single CTCs from 10 pts with MBC were identified and removed from the glass substrates. DNA was extracted, and the whole genome of isolated CTCs was amplified by using whole genome amplification method (Sigma). P53 mutations in exon 5, exon 6, exon 7 and exon 8 were assessed. As comparison, genomic DNA from formalin-fixed and paraffin-embedded (FFPE) from primary BCs of the same pts, was amplified using the same method.
Results: p53 mutations were found in 8 out of 10 CTCs, and in 4 out of 10 in primary BC samples. Of 8 mutations detected in CTCs, one silent mutation and 7 missense mutations were seen. One particular point mutation, R181L, previously assessed as functional mutation, was observed in 4 out of 8 CTCs. None of the 4 mutations (a silent mutation, one missense mutation and two different deletions) detected in tumor samples were found in CTCs. We validated that the mutations detected in CTCs were not artifacts occurring during genome amplification, by comparing p53 mutations between unamplified tumor genomic DNA vs. amplified samples.
Conclusion: Whole genome amplification based on extracting DNA from single CTCs using FAST, and identification of mutations such as those in p53, is feasible. The quantitative and qualitative discordance in detecting p53 mutations between CTCs and primary BCs may be due to CTCs acquiring new -possibly epithelial-mesenchymal transition-like-characteristics with metastatic potential as they evolve from the primary tumors or metastatic sites, or, technical issues (analyzing FFPE-preserved vs. CTCs, tumor heterogeneity) may contribute to our findings. Further assessment of the functionality of high frequent functional mutations such as R181L is warranted.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-12.
P4-09-08: Secretory Leukocyte Protease Inhibitor as a Differential Diagnostic Biomarker of Tumor Emboli in Inflammatory Breast Cancer.
Authors: Robertson FM , Ye Z , Chu K , Luo AZ , Wright MC , Jin J , Barsky SH , Cristofanilli M , Krishnamurthy S 
Published: June 2012

Abstract
Background: Inflammatory breast cancer (IBC) is the most aggressive and lethal variant of locally advanced breast cancer. Pathologically, IBC is characterized by the presence of nests of cells, defined as tumor emboli, that undergo lymphovascular invasion into the skin and chest wall and represent the metastatic lesion of IBC. Due to the distinct presentation of IBC, it is often misdiagnosed due to a lack of defined biomarkers that are specific for tumor emboli in biopsy samples of IBC patients. To date, the only validated marker that has shown to consistently identify IBC tumor emboli is the surface glycoprotein E-cadherin.
Materials and Methods: With the goal of identifying genes specifically expressed by IBC tumor emboli, the present studies performed whole transcriptome analysis of tumor emboli from skin punch biopsy samples from IBC patients and tumor emboli from the Mary-X pre-clinical model of IBC which were isolated using laser capture microdissection.
Results: Secretory leukocyte peptidase inhibitor (SLPI) was a gene identified as being highly expressed by tumor emboli. This gene was previously identified as a metastasis related gene, has been reported to be associated with poor prognosis in serous ovarian carcinoma and is implicated in mediating resistance to paclitaxel. Immunofluorescence staining and confocal microscopy revealed that SLPI is a robust marker of tumor emboli in skin punch biopsies from IBC patient and in Mary-X tumor emboli. SLPI differentially delineates between IBC tumor emboli and hair follicles present in the skin, which also stain with E-cadherin. An additional marker, Cytokeratin 15 (CK15), can be used in combination with SLPI to differentially identify the components of the skin that are CK15 positive, and IBC tumor emboli that reside within the skin, which are CK15 negative. Use of podoplanin antibodies, which stain lymphovascular endothelium, demonstrate that IBC tumor emboli that express SLPI protein, are completely encircled within the dermal lymphovasculature.
Conclusions: These studies are among the first to identify SLPI as a potential biomarker of tumor emboli in skin punch biopsy samples from IBC patients and in pre-clinical models of IBC. Studies are ongoing to establish the molecular function and role of SLPI in mediating the survival and invasion of IBC tumor emboli. Collectively, these studies are the first to identify SLPI as a potential biomarker of IBC tumor emboli in skin punch biopsy samples. In addition to serving as a potential biomarker of tumor emboli, SLPI may also serve as a therapeutic target for development of approaches to eradicate IBC tumor emboli.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-08.
P4-09-20: Expression Profile of Interleukin 17B and the Receptor IL-17BR in Clinical Breast Cancer.
Authors: Sanders AJ , Mansel RE , Mason MD , Jiang WG 
Published: June 2012

Abstract
Introduction:
Interleukin 17B (IL-17B) is a member of the interleukin 17 cytokine family. Members of this family have been implicated in conditions such as autoimmune diseases and the inflammatory response. A number of studies have examined the role of IL17A in cancer progression and angiogenesis and shown a variety of functions, both pro- and anti- tumorigenic. Currently there is little data on IL-17B and the receptor IL-17BR and their involvement in cancer progression. The current study looks at the expression profile of IL-17B and IL-17BR in a clinical breast cancer cohort.
Methods:
The expression profile of IL-17B and IL-17BR was examined in a cohort of human normal breast and breast cancer specimens (normal, n = 34; tumour, n = 109). IL-17B and IL-17BR transcript expression in the samples was analysed using Q-PCR and compared to clinical and pathological data.
Results:
Both IL-17B and IL-17BR expression seemed to correlate with NPI staging. IL-17B levels were low in patients with NPI-1 or -2 cancers (median values 3.1 and 1.1 respectively), with highest levels of IL-17B being observed in the poorer prognosis NPI-3 group (median value 206.9; p = 0.07 NPI-1 vs NPI-3 and p = 0.01 NPI-3 vs NPI-2). Similar to this IL17B levels in TNM stage 1 cancers were significantly lower than those in higher TNM stages (TNM1 median value = 0.3 vs grouped TNM234 median value 10.3, p = 0.03). IL-17BR expression also tended to increase with NPI staging (IL-17BR median expression, NPI-1 = 0.0, NPI-2 = 0.04 and NPI-3 = 1.59; NPI-1 vs NPI-3 p = 0.07). Additionally, levels of IL-17BR were found to be significantly lower in background tissue compared to cancer tissue (median values 0.00 vs 0.01 respectively, p = 0.014).
Conclusion:
IL-17BR expression seems to be higher in tumour tissue compared to normal background tissue. Additionally, expression of IL-17B and IL-17BR both appear to be associated with higher NPI stage, particularly in the poor prognostic NPI-3 group. Expression of IL-17B seems to be elevated collectively in TNM stage 2, 3 and 4 compared to the better prognostic TNM1 stage. Together the data suggests that IL-17B and IL-17BR expression may be useful molecules to identify poorer prognostic breast cancers in patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-20.
P4-09-35: Co-Expression of Ki-67 Is Critical for Outcome of Cyclooxygenase-2 Positive Breast Cancer.
Authors: Park S , Koo JS , Lee JS , Hwang H , Ko S , Kim SI , Park B-W 
Published: June 2012

Abstract
Background
The purpose was to investigate the implications of cyclooxygenase-2 (COX-2) and Ki-67 expression on the progression and prognosis of breast cancer.
Methods: COX-2 and Ki-67 levels were immunohistochemically determined using tissue microarrays of 1,028 breast tumors treated between November 1999 and August 2005. COX-2 and Ki-67 levels were compared by tumor progression and clinicopathological parameters were investigated in association with both markers status which was divided into 3 subgroups: COX-2(+)/Ki-67(+), COX-2(+)/Ki-67(−), COX-2(−)/Ki-67(any).
Results: COX-2 expression was significantly higher in intraductal carcinoma and progressively decreased in small T1 lesions and then in T2-T4 tumors, but Ki-67 was significantly expressed at high levels in T2-T4 lesions than in intraductal or T1 carcinomas. COX-2 expression was positively associated with favorable parameters such as older age at diagnosis, smaller size, well-differentiation, hormone receptor-positivity, and was inversely associated with Ki-67 expression. Among 816 invasive tumors, COX-2 expression alone was not related to outcomes. In combination with Ki-67 expression, however, COX-2(+)/Ki-67(−) tumors were significantly associated with favorable characteristics including HER2−negativity and demonstrated favorable outcomes. COX-2(+)/Ki-67(+) tumors showed unfavorable factors and the worst outcomes. COX-2(−)/Ki-67(any) subgroup presented intermediate prognosis. Statistical significance of COX-2 combined with Ki-67 was maintained in Cox's models adjusting for clinicopathological parameters among not only whole population but also ER-positive subgroup.
Conclusions: Our study suggests that COX-2 is expressed in early phase of breast cancer development and is associated with favorable prognostic markers. But co-expression of high Ki-67 proliferative index could indicate an aggressive phenotypic change in COX-2 positive breast cancer. The mechanisms should be further investigated.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-35.
P4-11-10: Perceptions, Knowledge and Satisfaction with Contralateral Prophylactic Mastectomy among Young Women with Breast Cancer.
Authors: Tracy MS , Meyer ME , Sepucha K , Gelber S , Hirshfield-Bartek J , Troyan S , Morrow M , Schapira L , Come S , Winer E , Partridge AH 
Published: June 2012

Abstract
Background: There has been an increasing prevalence of contralateral prophylactic mastectomy (CPM), particularly among younger women with breast cancer. There has been limited research evaluating patient preference, knowledge and decision-making regarding this issue.
Methods: We surveyed women who had bilateral mastectomy who were enrolled in a multicenter, longitudinal cohort study of women diagnosed with breast cancer at age 40 and younger. The CPM survey included 23 items on decision making, knowledge, and satisfaction with CPM.
Results: Of the 550 patients enrolled as of November 2010, 157 (28.5%) had bilateral mastectomy, of whom 124 completed the CPM survey (response rate 79%). Women with bilateral breast cancer (3) or bilateral prophylactic (1) indications for surgery were excluded. Median age at diagnosis was 37 years (range 26–40); 26 women (21%) reported having a genetic mutation (21 BRCA1 and 5 BRCA2). Excluding mutation carriers, women estimated that a median of 10 of 100 women (range 0–90) would develop contralateral breast cancer in the 5 years after unilateral breast cancer treatment and that 5 of 100 women (range 0 — 98) treated with CPM would develop contralateral breast cancer. Eighteen percent of all respondents believed that women who undergo bilateral mastectomy live longer. Women were asked the importance of potential reasons for undergoing CPM (see Table 1). Eighty-two percent of women were “extremely confident” in their decision to undergo CPM and 92% would “definitely” still choose CPM.

Conclusion: Young women with breast cancer have high rates of CPM. Many young women who have undergone CPM overestimate the risk of contralateral disease and the benefits of CPM, including believing that CPM will prevent metastasis and extend life. Interventions to counsel young women with early breast cancer to help them make optimal surgical treatment decisions are needed.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-10.
P4-12-10: A Prospective Study of Physical Activity Patterns and Changes in Breast Cancer Patients during Active Breast Cancer Treatment.
Authors: Kim I-R , Choi E-K , Nam S-J , Lee J , Lee S-K , Yang J , Noh DY , Han W , Cho J 
Published: June 2012

Abstract
Purpose Physical activity (PA) has been shown to benefit cancer patients’ physical functioning, emotional well-being, and symptom management. Moderate PA may reduce the side effects of breast cancer treatment and improve quality of life, but most of the studies have been conducted after active treatment was completed and there is little data on patterns of PA during active treatment. This study aims to evaluate patterns and changes in physical activity among breast cancer patients during active treatment.
Patients and Methods We recruited 411 women with non-metastatic breast cancer between July 2010 and Dec 2010 from two major cancer hospitals in Seoul, Korea. Trained researchers interviewed participants at enrollment (before surgery), and at 2 weeks, 3 months, and 6 months post surgery. Intensity and duration of PA were assessed using the Minnesota Leisure Time Physical Activity Questionnaire, and energy expenditure (the average calories spent per day) was calculated as metabolic equivalents (METs). Quality of life (EORTC), fatigue (BFI), socio-demographic and clinical characteristics were also assessed. After excluding 15 patients with recurrence during follow-up and 65 patients were lost to follow-up, the final sample size was 331 patients (80.5%).
Results The mean (SD) age and BMI of study participants were 46.4 years and 23.3kg/m2 (SD 3.35). 83.7% of women had lumpectomy, and 70.6% and 85.9% had adjuvant chemotherapy and radiotherapy respectively. Breast cancer patients were most likely to spend their energy in lifestyle (walking and driving) and leisure (shopping, reading, and watching TV) activities but spent little energy in sport activities (Table).

Conclusion PA declined after the surgery and gradually recovered at 3 and 6 months post surgery but it did not return to the baseline level. Breast cancer patients may need encouragement and support to perform more intensive physical activities during active treatment.
*Acknowledgement: The research was accomplished by the support from AMOREPACIFIC and Korea Breast Cancer Foundation.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-10.
P4-14-03: Support Groups in Breast Cancer: An Evidence Based Assessment of 1606 Patients with Concerning Topics for Support Group Discussion and Presentation.
Authors: Gralla RJ , Morse KD , Rittenberg CN , Petersen JA , Rosen LM , Lesser M 
Published: June 2012

Abstract
Background
Cancer support groups are conducted at most cancer centers. Although there is increasing demand among patients and families for support groups, little data exist outlining which topics patients and caregivers consider as most important for support group discussion and presentation. We conducted a large web-based anonymous survey to determine preferences of patients and caregivers for cancer support groups, including 1606 individuals with breast cancer and 3723 with other malignancies.
Methods: The established patient base of NexCura®, a web-based information resource, was used to survey registered patients and caregivers in this on-line assessment. Participants ranked 26 topics on a 5-point Likert scale which evaluated the importance of each item. Demographic characteristics, clinical factors, and support group content preferences were assessed.
Results: There were 4402 respondents to the invitation to participate, and 3723 patients and caregivers elected to participate (85%). Characteristics included for all 3723 patients: 70% women, mean age 58 (range 20–89). For the 1606 patients with breast cancer, 99.8% were women, the mean age was 56 (range 27–88); 53% were free of cancer. For the whole group, the four most common cancers were breast 45%, prostate 15%, lung 6%, and colorectal 5%. 90% of participants were patients and 10% were caregivers. 80% of participants rated all 26 topics. The table below shows rankings by the top 2 categories (the percent ranking each topic as “Very Important” or “Important”) of the 10 highest rated topics (and the rank order for each item) for patients with breast cancer and for all patients.

Conclusions: 1) This is the largest survey of patients and caregivers concerning support groups for patients with breast cancer and for a general cancer population. 2) Patients with breast cancer ranked most topics similarly to the general cancer population; however, topics dealing with fatigue and stress management were somewhat more highly ranked by those with breast cancer. 3) Physical, psychological, and communication issues were the most highly ranked issues by breast cancer patients and families. 4) These results should guide the content of support groups to meet the needs of patients and caregivers.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-03.
P4-17-02: Whole-Brain Radiation Therapy Plus Concomitant Temozolomide for the Treatment of Brain Metastases from Breast Cancer: A Randomized Prospective Multicenter Phase II Study.
Authors: Kirova YM , Hajage D , Gerber S , Le Scodan R , Pierga J-Y , Bourgier C , Campana F , Asselain B , Fourquet A , Levy C 
Published: June 2012

Abstract
BACKGROUND: A previously published study of temozolomide (TMZ) concurrent with whole-brain radiation therapy (WBRT) reported significant improvement in response rates and a nonsignificant trend toward improved overall survival compared with WBRT alone in patients with brain metastases in different type of tumors. A prospective randomized phase II trial of concurrent WBRT and TMZ versus WBRT alone was conducted to assess whether the concurrent use of WBRT-TMZ resulted in measurable radiological response differences at 6 weeks after the treatment in homogeneous population of breast cancer (BC) patients.
PATIENTS AND METHODS: In this intent-to-treat study, patients with metastatic breast cancer to the brain and not suitable for surgery or radio-surgery were enrolled in a randomized prospective multicenter phase II study between February 2008 and December 2010. Patients received temozolomide 75 mg/m(2)/day (days 1–15) concurrently with WBRT 30 Gy/10 fractions. Patients were stratified by type and metastatic sites. The (MRI) response at 6 weeks was the main criteria; response was defined as complete (CR) or partial response (PR). Initial and follow-up MRI were realized on a 1.5T unit (Siemens) by axial SE-T1 WIs and FLAIR WIs with GdDTA injection, EG-3DT1 WIs after GdDTPA. Five target lesions (over 10 mm greatest diameter) were measured in their 3 dimensions. Non measurable lesions were noticed."The treatment tolerance and clinical responses were also evaluated. The study was designed according to a modified Fleming two-stage plan based on response hypotheses of 30% (H0) versus 50% (H1). Twenty or more responses among 50 subjects were needed to declare the treatment effective, with risk errors alpha 9% and beta 7%.
RESULTS: One hundred metastatic breast cancer patients were enrolled in the study, as following: 49 in WBRT-TMZ and 51 in WBRT groups. The median age was 55 years [range, 29–79]. The median follow-up was 12 weeks [range, 1–94]. There were 15/49 (31%) partial responses (PR) in WBRT-TMZ and 18/5 1(35%) PR in WBRT group. No complete responses were observed. The symptoms relief was obtained in 27/49 and 31/51 pts, respectively. The treatment tolerance was acceptable in both groups.
CONCLUSION: The benefit of adding TMZ to WBRT was not confirmed at 6 weeks. The tolerance was good in both groups. Longer follow-up is needed to evaluate the combination of TMZ with WBRT in terms of progression free survival.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-02.