bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Clinical Study of Protection of Nail Change and Skin Toxicity by Using a Frozen Glove in Japanese Patients with Early Breast Cancer Treated by Docetaxel and Cyclophosphamide (TC) [TBCRG-03 Study].
Authors: Hayashi T. , Fujita T. , Mase T. , Nakano S. , Wada M. , Kashizuka T. , Sugiura H. , Mizuno T. , Iwata H. , Ohashi Y. 
Published: December 2010

Abstract
Background: The combination docetaxel with cyclophosphamide (TC) regimen is one of standard treatment for early breast cancer patients. TC regimen has been widely used in Japan. However, a management for adverse event such as especially edema and nail/skin toxicity by docetaxel is very important due to give a completely full dosage. This multicenter phase II study was designed to evaluate the protection of nail and skin toxicity by using a frozen glove for early breast cancer patients treated by TC.Methods: Four cycles of docetaxel (75mg/m2) and cyclophosphamide (600mg/m2) administered intravenously (i.v.) every 21 days after surgery for primary breast cancer. All patients were attached frozen glove at right or left hand (protected hand) from 15 minutes before to 30 minutes after administration of docetaxel. The other hand (control hand) of same patient is not attached frozen glove between a administration of TC. Safety was assessed every cycle after the start of treatment. Primary endpoint is comparison the rates of nail and skin toxicity between protected and control hand. Secondary endpoints are feasibility of adjuvant TC regimen and adverse events by frozen glove in Japanese women.Results: Fifty two patients were enrolled from September 2007 to June 2008. The nail changes (grade 1 and 2) was occurred in 10 events (19.2%) and 19 events (36.5%) at protected and control hand, respectively. The skin toxicity was occurred in 14 events (26.9%, G1:8, G2:6) and 21 events (40.4%, G1:14, G2:7) at protected and control hand, respectively. The appearance of nail and skin toxicity was significantly decreased at protected hand than control hand (p=0.01). Overall, 41 patients (78%) completed the planned four cycles of TC without dose reductions or study discontinuation. One patient discontinued because of hematological toxicity defined as discontinuation by protocol. The dose reductions were necessary in 10(19%) patients because of hematological (febrile neutropenia) and non hematological toxicity by TC. Grade 3 and 4 adverse events (AEs) were neutropenia (G3:3.9%, G4:21.6%), febrile neutropenia (21.2%), fatigue (1.9%) and dermatitis (3.8%). Grade 1 or 2 AEs frequently observed (more than 20%) were dermatitis such as rash (45%, G1:29.4%, G2:15.7%), pigmentation, nausea, anorexia, disturbance of taste, tear dropping, fatigue, edema and peripheral sensory disturbance. However, there are no adverse events by frozen glove.Conclusion: TC is feasible regimen for early Japanese breast cancer patients after surgery. Frozen glove may be useful procedure which protected the nail and skin toxicity. Furthermore, it is necessary to protect the severe dermatitis due to completely performed planned TC treatment after surgery in Japan.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 808.
Extra-Nuclear Estrogen Receptors: Functions in Breast Cancer.
Authors: Levin E. , Levin E. 
Published: December 2010

Abstract
Pools of classical estrogen receptors alpha and beta exist in various cellular locations including the nucleus, plasma membrane, and in cytoplasmic organelles (e.g.-mitochondria). The roles and importance of the extra-nuclear receptors are under investigation but in some women with breast cancer, membrane ERalpha greatly exceeds the nuclear ER pool. To understand how these receptors traffic to the plasma membrane and function, we took a proteomic approach that identified Heat Shock Protein 27 (Hsp27) as an important promoter of membrane ER localization. Hsp27 physically interacts with the ERalpha monomer, promoting palmitoylation of the sex steroid receptor, leading to enhanced association with caveolin-1 in cytoplasm and subsequent trafficking to the membrane. Using RNAi for Hsp27, this protein was shown to be necessary for ERalpha to localize to the membrane and signal through ERK and PI3 kinase, accounting for about 50% of total cell proliferation induced by estradiol. Membrane ERalpha and not nuclear ERalpha also blocks DNA repair signaling through ATR and ATM kinases in both normal breast epithelial cells and breast cancer cells (Mol Biol Cell 20:3374,2009).This occurs in the setting of radiation or chemotherapy-induced cell damage, in-vitro. Inhibiting kinase signaling leads to loss of cell cycle checkpoints, delay of DNA repair, inhibition of p53 function, and enhanced chromosomal damage upon exposing cells to gamma radiation. As for ERbeta, we find that this receptor exists mainly in extra-nuclear, mitochondrial locations in breast cancer cell lines. There is evidence that the cytoplasmic ERbeta 2 isoform correlates to a poor prognosis in women with breast cancer (Clin Canc Res, 2008). We found that mitochondrial ERbeta regulates reactive oxygen species formation. This function importantly participates in the response to tamoxifen, sensitivity (apoptosis) versus resistance (survival and growth), in several breast cancer cell lines. Mechanisms involved will be explored at the meeting. In summary, new and potentially important functions of extra-nuclear ERalpha and ERbeta could contribute to breast pathobiology.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr BS2-1.
Value of axillary ultrasound and cytology in assessing nodal status preoperatively.
Authors: Absar MS , Barr N , Wilson M , Beetles U , Knox F , Morris J , Bundred NJ 
Published: December 2010

Abstract
Abstract #1007
Preoperative identification of axillary node involvement in early breast cancer allows correct surgical procedures to be performed and avoids second axillary operations. We compared preoperative axillary assessment using ultrasound ± cytology with the eventual histopathological results to identify the accuracy of preoperative axillary node assessment.&#x2028; Methods: Preoperative axillary ultrasound was used to identify the presence of suspicious or malignant nodes which were then confirmed with cytological assessment to allow management decisions regarding axillary clearance (or sentinel node biopsy (SNB) if nodes appeared negative).&#x2028; Results: Overall 79/365 (21%) early breast cancer patients had suspicious or malignant nodes on ultrasound, of which 78 were confirmed on cytology, thus avoiding an unnecessary SNB operation in these patients. Ultrasound and cytology accurately identified patients with ER negative (P=≤0.001), high grade (P=≤0.001) and large size tumours ≤20mm (P=≤0.001), with involved nodes. Only 11% ER negative compared to 46% ER positive tumours were incorrectly classified (P=0.002). In contrast ER positive, low grade, small tumours were most likely to have a false negative axillary assessment. Specificity of cytological assessment of nodes was 99% and sensitivity 54%.&#x2028; Conclusions: Axillary ultrasound combined with cytological assessment of suspicious nodes accurately identifies majority of women who require axillary clearance.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1007.
The value of preoperative axillary ultrasound staging in the management of early breast cancer.
Authors: O'Mahony DM , Quinn LM , Hafeez A , Dunne BM , Griffin M , Wilson GF , McDermott RA , Boyle TJ , Connolly EM 
Published: December 2010

Abstract
Abstract #1023
Background: The prognosis of breast cancer is strongly associated with the presence of metastatic disease in the axillary lymph nodes at the time of diagnosis. Sentinel lymph node biopsy (SLNB) is the current standard of care for staging a clinically negative axilla in early breast cancer. Approximately 25% of women with early stage breast cancer undergoing SLNB are node positive and require completion axillary lymph node dissection (ALND). Ultrasound guided fine needle aspiration cytology (FNAC) of axillary lymph nodes is a minimally invasive technique that can be used preoperatively to stage the axilla in breast cancer patients, reducing the number of operative procedures required for staging and local control of disease. Aim: To determine the sensitivity and specificity of ultrasound guided axillary FNAC to detect positive axillary lymph nodes in breast cancer patients and to determine the number of patients who avoided unnecessary SLNB. Methods: Newly diagnosed invasive breast cancer patients were prospectively followed from January 2007 to June 2008. Patients with stage IV breast cancer, clinically node positive disease and patients who did not proceed to surgery were excluded. Criteria for a suspicious sonographic axillary node included diffuse cortical thickening &gt;3mm, focal nodular cortical thickening and a mass-like appearance with loss of the fatty hilum. Results: 133 patients who met the inclusion criteria were diagnosed with invasive breast cancer between January 2007 and June 2008. Median age was 60 [21-87]. 49 patients had T1 tumours, 77 patients had T2, and 7 patients had T3 tumours. 126 (95%) patients had axillary ultrasounds, 44 ( 35%) of which showed abnormal axillary lymph nodes. 38 ( 86%) of these 44 patients proceeded to ultrasound guided axillary FNAC and 27 (71%) of these were positive for malignant cells. All patients with positive axillary nodal FNAC underwent axillary clearance and all had positive nodes on final histopathology. The median number of positive nodes was 2, range was 1 to 21. 26 (20%) patients avoided unnecessary SLNB. 82 patients had a negative axillary ultrasound and 27 of these had axillary node positive disease. The median number of positive nodes was 1, the range was 1 to 8.&#x2028; &#x2028; Conclusion: Ultrasound guided axillary FNAC has a high specificity and positive predictive value in radiologically suspicious nodes. A positive FNAC allows definitive treatment of the axilla in radiological node positive patients and avoids the unnecessary step of SLNB.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1023.
Anti-angiogenic effects of tamoxifen in breast cancer by decreased secretion and reduced nuclear accumulation of angiogenin.
Authors: Nilsson UW , Dabrosin C 
Published: December 2010

Abstract
Abstract #1033
Angiogenin, is a 14.2 kD polypeptide member of the RNase A superfamily of enzymes with potent angiogenic activity. Angiogenin binds to endothelial cells and induces proliferation, cell migration, and invasion. Nuclear accumulation of angiogenin is essential for its angiogenic activity. In breast cancer, increased angiogenin expression has been associated with the transition from normal to invasive breast carcinoma and to ER expression. We have previously reported a pro-angiogenic action of estradiol and anti-angiogenic activity of tamoxifen in breast cancer by regulation of VEGF secretion and generation of endostatin. In this paper we investigated if estradiol and/or tamoxifen affected angiogenin. We show that estradiol increased and tamoxifen decreased angiogenin secretion of human breast cancer cells in culture. In vivo, in solid human breast cancers in nude mice, tamoxifen therapy decreased angiogenin extracellularly, sampled using microdialysis. Moreover, estradiol-induced angiogenin derived from cancer cells significantly increased human endothelial cell (HUVEC) proliferation. Adding tamoxifen to the estradiol treatment as well as an antibody against angiogenin, reversed this increase. Additionally, exposure of tamoxifen to HUVEC in culture significantly decreased the endogenous secretion of angiogenin as well as the translocation of angiogenin to the nucleus. We conclude that angiogenin expression is estrogen-regulated in human breast cancer cells. In addition, decreased secretion of angiogenin by cancer and endothelial cells, and a restrained nuclear accumulation of angiogenin, may suggest novel anti-angiogenic mechanisms of tamoxifen. This may be a target for anti-estrogen therapeutic options in the future.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1033.
Angiogenesis in breast cancer: comparison between three vascular endothelial markers.
Authors: da Silva BB , Lopes-Costa PV , dos Santos AR , Sousa-Júnior EC , Facina G , Nazário AC 
Published: December 2010

Abstract
Abstract #1037
Background: Controversial results have been reported on the three vascular endothelial markers most commonly evaluated in breast carcinomas. The objective of this study was to evaluate the quantification of angiogenesis by comparing the performance of anti-Factor VIII related antigen, anti-CD31 and anti-CD34 monoclonal antibodies to assess microvessel density in breast cancer. Methods: Twenty-three postmenopausal women diagnosed with stage II breast cancer and submitted to mastectomy or segmentectomy were evaluated. The monoclonal antibodies used were anti-Factor VIII, anti-CD31 and anti-CD34. Microvessels were counted in the areas of highest microvessel density using a magnification of 200x in 10 random fields. Microvessel density was defined as the mean number of microvessels counted in 10 fields. The data were analyzed using the Kruskal-Wallis nonparametric test (p&lt;0.05). Results: Mean microvessel densities with anti-Factor VIII, anti-CD31 and anti-CD34 were 4.16, 4.09 and 6.59, respectively. Microvessel density as detected by anti-CD34 was significantly greater than that detected by anti-CD31 or anti-factor VIII (p&lt;0.0001). There was no statistically significant difference between microvessel density detected by anti-CD31 and anti-Factor VIII (p=0.4889) (see Table 1 and Figure 1).&#x2028; &#x2028; [figure1]Discussion: In the present study, despite the current controversies, a higher density of microvessels and a greater intensity of staining were found when anti-CD34 was used in comparison with anti-CD31 and anti-Factor VIII related antigen in paraffin-fixed samples of infiltrating ductal breast carcinoma from postmenopausal women. These findings justify the increasing use of this monoclonal antibody in the study of angiogenesis, not only in breast cancer but also in other neoplasias.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1037.
Differences in outcome of young breast cancer patients according to BRCA1 mutation status.
Authors: Gabrys D , Trela K , Boratyn-Nowicka A , Suwinski R , Grzybowska E , Behrendt K , Galwas K , Wojcieszek P , Idasiak A , Thames H 
Published: December 2010

Abstract
Abstract #1044
Introduction&#x2028; 5 to 10 % of all breast cancer and 25 % of early onset breast cancer are inheritable, which may be caused by mutations of tumour suppressor genes such as BRCA1. Moreover, the issue of a familial breast cancer has raised much attention in recent years due to numerous medical and social implications. In the present paper we investigate the clinical characteristic and outcomes of younger (&lt;50 years old) breast cancer patients with BRCA1 mutation in comparison to patients without this germline mutation.&#x2028; Methods and Materials&#x2028; This is an ongoing study and patients will be enrolled till end of 2008. Till now we followed 495 breast cancer patients who were diagnosed before age 50 and were asked to provide a blood sample for BRCA1 mutation screening. We compared contralateral breast cancer and ovarian cancer incidence, disease free, metastases free, and overall survival, between BRCA1 mutation carriers and non-carriers.&#x2028; Results&#x2028; BRCA1 mutations were detected in 90 breast cancer patients (5382insC in 60 patients, 300T/G in 18 pts, 185delAG in 10 pts, and 4153delAin 2 pts); the remaining 405 women did not carry the mutation. BRCA1 related tumours showed higher grade, higher Ki67 protein expression, more frequent negative oestrogen, progesterone, HER2-neu receptor status. Patients with BRCA1 mutation had a higher incidence of bilateral breast (40% compared to 10% in non mutated patients) and ovarian cancer (16% compared to less than 1% in non mutated patients. 10-years OS (overall survial) was 81% in no BRCA1 mutation patients compare to 88% in mutated BRCA1 patients (p=0.7), 10-years DSF (local-regional and distant failure) was 81% vs. 67% (p=0.8), 10-years MFS (metastases free survival) was 85% vs 71% (p=0.1), and 10-years RFS (recurrence free survival) was 90% vs. 80% (p=0.1) respectively.&#x2028; Multivariate Cox analysis for DFS showed that node ratio &gt; 12% (HR=2.12), increasing tumour diameter (HR=1.23), experienced significantly decreased DFS. Furthermore, overall survival analysis also showed that node ratio &gt; 12% (HR=2.65), increasing tumour diameter (HR=1.23), experienced significantly decreased OS. There is an insignificant trend for patients without BRCA1 mutation and younger to have worse DFS (HR=1.28) and worse OS (HR=2.23).&#x2028; Conclusions&#x2028; Patients with BRCA1 mutations have higher incidence of bilateral breast and ovarian cancer which imposes the need for frequent and careful follow-up after therapy. Node ratio and tumour diameter are the strongest prognostic factors. A final conclusion will require more patients and longer follow up.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1044.
Lobular breast carcinoma as a possible candidate phenotype for recessively inherited breast cancer.
Authors: Olsson HL 
Published: December 2010

Abstract
Abstract #1045
Background:There are reasons to believe that beside dominant inheritance of breast cancer other modes of inheritance as recessive inheritance ought to exist. Studies have however failed to find recessive inheritance.Patients developing lobular carcinoma who often show multifocal and bilateral presentation could be a candidate phenotype for such a recessive disorder. Further a previous hypothesis suggests that lobular carcinomas develop from a more mature breast tissue later in reproductive life than f.i. tumours of ductal origin. Therefore lobular carcinomas ought to present at a later age and breast cancer without other cancer sites would be the predominant tumour occurring in such families.&#x2028; Objective: To study breast cancer patients and relate their type of family history (vertical, horizontal or combined) to tumour histology and then especially the number of lobular carcinomas in relation to age at presentation in order to possibly identify a recessive phenotype for breast cancer.&#x2028; Material and methods: Two different sets of patients have been used. First from a consecutive series of breast cancer patients(n=1682) seen at the Department of Oncology, University Hospital, Lund between 1980-2002, randomnly seen by one physician, a comprehensive standardized family history was taken. Family history was classified into 4 groups; vertical (sister-sister), horizontal (mother-daughter), combined or none. Family history was related to whether the patient had developed lobular carcinoma and the age at tumour presentation (≤50 years or above 65 years). Secondly in patients with ≥4 malignant tumours of which at least one is a breast cancer, n=67, (identified through the population based cancer registry) extended family trees were used and related to the tumour histology of the proband (lobular cancer or not).&#x2028; Results: Patients with a horizontal family history (sister-sister) had more lobular carcinomas (18.8%) compared with the other groups (11.3%), p=0.05. The relationship was strongest for patients with disease above 65 years of age (31% lobular carcinoma for horizontal vs 10.9% for the others), p=0.0003, but not significant for disease presentation below age 50.&#x2028; Conclusion: A horizontal family history (sister-sister) was significantly associated with lobular carcinoma developing at higher ages. These type of families may be the phenotype for studies of recessive genes in breast cancer, while in patients with multiple tumours of various types lobular carcinoma is not associated with a horisontal family history. This indicates that the possible phenotype for a recessive disorder encompassing lobular carcinoma should exhibit breast cancer as the only tumor type in the family.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1045.
TP53 mutation is an early event in breast cancer progression.
Authors: Zhou W , Muggerud AA , Vu P , Due EU , Sørlie T , Børresen-Dale A , Wärnberg F , Langerød A 
Published: December 2010

Abstract
Abstract #1047
Background: In breast cancer, previous studies have shown that somatic TP53 mutations cause a more aggressive disease with poor clinical outcome and may impact treatment response. Although TP53 mutation is considered to be an early event in breast cancer, the timing of TP53 mutations is not known, and there are controversies regarding the cellular origin and linear model of breast cancer. The purpose of this study was to investigate whether TP53 mutations are early events in breast cancer progression.&#x2028; Methods: From a population-based cohort of women diagnosed between 1986 and 2004 either with a pure ductal carcinoma in situ (DCIS), a pure invasive cancer (&lt;15mm) or a mixed lesion (i.e. invasive cancer with a DCIS component), we included 118 women with stored frozen tissue. Mixed lesions were microdissected using LCM (laser capture microdissection) on a PALM slide to separate in situ and invasive tumor cells. DNA was isolated using phenol-chloroform extraction. The entire coding sequence of TP53 was analyzed for mutations by direct sequencing on a 3730 DNA analyzer.&#x2028; Results: Of 118 tumor samples, 19 were detected with a TP53 mutation; five 5 of 32 (15.6%) pure DCIS, 4 of 38 (10.5%) pure invasive cancers and 10 of 48 (20.8%) mixed lesions. In the mixed lesions, both the invasive and the DCIS component showed the same mutation in all 5 cases where we successfully could microdissect the two components separately. Pure DCIS demonstrated missense mutations (4/5, 80%) more frequently than pure invasive cancers (2/4, 50%) and mixed lesions (4/10, 40%), although this difference was not statistically significant (p=0.3). Also, the frequency of missense mutations in the DNA binding domain was not statistically different between the three groups.&#x2028; Conclusion: TP53 mutation is likely an early event in breast cancer, occurring previous to or in the in situ stage. Presence of the same mutation in both DCIS and invasive component from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression into invasive cancer is less clear and may vary between subtypes of breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1047.