bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bevacizumab (BEV) and paclitaxel (PAC) every two weeks as first-line treatment for advanced breast cancer (ABC). Preliminary results.
Authors: Ardavanis A , Doufexis D , Kountourakis P , Malliou S , Karagiannis A , Kardara E , Sykoutri D , Rigatos G 
Published: December 2010

Abstract
Abstract #4121
Background: Targeting angiogenesis is nowadays one of the most promising approaches for breast cancer. BEV, an anti- VEGF monoclonal antibody, was recently approved in combination with PAC for first-line treatment of ABC. Preliminary of a biweekly regimen of the combination are presented here.&#x2028; Patients-treatment: P with ABC were to receive, after appropriate premedication, BEV 10 mg/kg and PAC 135 mg/m2 with growth factors where necessary, q2weeks for six months; responders and stabilized P had to receive maintenance with BEV 15 mg/kg q3weeks until progression. This regimen was chosen instead of the established one standard ( PAC weekly ) for better patient convenience, while maintaining the same dose intensity for both drugs (for PAC the DI of the 3-weekly 175/m2 schedule).&#x2028; Results: Thirty one ( 31 ) , HER 2 negative women aged 39-63 ( average 55 )were enrolled. Toxicity was in general acceptable: Neutropenia/leucopenia grade III/IV, anaemia I/II, neuropathy grade III and manageable hypertension in 5, 3, 7, 6 P ( 16%, 9%, 22%, 19% ) respectively were observed. Efficacy: Two P experienced a complete response, 12 responded partially, 12 P with stable disease and 5 progressed. Overall response and disease control rates were 45% and 83% respectively. Results for PFS and OS are still immature.&#x2028; Conclusion: This biweekly BEV/PAC combination seems to be active with acceptable toxicity in ABC. The activity observed in the small-size population of this study should be assessed in a larger number of patients; if confirmed, BEV/PAC/q2w might represent an interesting alternative option for this group of patients as it has a clear advantage for patient's convenience over the weekly regimen contributing to QoL preservation and saving of resources.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4121.
HER-2 and topoisomerase IIa gene alterations in male breast cancer.
Authors: Rudlowski C , Wardelmann E , Merkelbach-Bruse S , Buettner R , Kuhn W , Schildhaus H 
Published: December 2010

Abstract
Abstract #4128
Background:&#x2028; In accordance to the guidelines for female breast cancer and due to more advanced tumor stages at diagnosis primary male breast cancer (MBC) is treated predominantly with anthracycline-based chemotherapeutic regimens. However, amplification of the HER2 and topoisomerase IIalpha (TOPO2A) genes has been linked to the effects of anthracyclines in female breast cancer. Presently no data are available reporting the percentage of TOPO2A amplification/deletion and its potential clinical impact on MBC. Here we present first data about HER2 and TOPO2A genomic alteration in MBC.&#x2028; Patients and Methods:&#x2028; We studied HER2 amplification and TOPO2A amplification/deletion (by fluorescence in situ hybridization) and HER2 protein expression (by immunohistochemical analysis) in 96 primary invasive MBC's using tissue microarrays. A gene copy number/chromosome 17 copy number ratio of 2.0 respectively 1.8 or higher indicated amplification of HER2 and TOPO2A. A TOPO2A/chromosome 17 ratio of less than 0.8 indicated gene deletion. In addition, HER2 protein expression was scored according to standard HercepTest guidelines (DAKO, Carpenteria, CA). Tumor characteristics and follow-up data were available and correlated with HER2/TOPO2A gene alterations and HER2 protein expression.&#x2028; Results:&#x2028; 91/96 cases were evaluable for TOPO2A/HER2 assessment. HER2 gene amplification were found in 6 cases (6,25%) of which 3 were classified as 3+, 2 as 2+ and 1 as 1+ positive for protein expression. TOPO2A amplification/deletion showed 3 patients (3.1%), 2 with amplification and one with a deletion. Only one patient had both HER2 and TOPO2A gene amplification. HER2/TOPO2A gene alterations were not related to the tumor characteristics, response to therapy or the patients survival.&#x2028; Conclusion:&#x2028; In female breast cancer recent studies have suggested that deletions or amplifications of the TOP2A gene are associated with poor prognosis and predictive of greater response to anthracycline-containing than to non-anthracycline-containing regimens. In this study group both HER2 and TOPO2A gene alterations were rare events. A simultaneous amplification was observed in only one case. Our data for MBC suggest that due to the low number of TOPO2A gene amplification/deletion the clinical significance of TOPO2A is of limited value. Based on these findings the role of anthracycline-containing regimens for MBC has necessarily to be defined.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4128.
Matched-pair analysis of female and male breast cancer: a comprehensive cohort study.
Authors: Foerster R , Foerster FG , Wulff V , Schubotz B , Lange R , Habeck J , Baaske D , Rudlowski C 
Published: December 2010

Abstract
Abstract #4129
Introduction:&#x2028; Male breast cancer (MBC) is a rare disease accounting for approximately 1% of all breast carcinomas. Due to the low incidence treatment guidelines based on prospective studies are lacking. Presently treatment recommendations are derived from the standards for female breast cancer. However, those approaches might be inadequate because of distinct gender specific differences in tumor biology of breast cancer. This study was planned in order to elucidate potential differences between female and male breast cancer in both tumor biological behavior and clinical practice.&#x2028; Patients and Methods:&#x2028; MBC diagnosed 1995-2007 (region Chemnitz/Zwickau, Saxony, Germany) was retrospectively analyzed. Tumor characteristics, treatment and follow-up of the patients were documented. In order to highlight potential differences matched-pairs of female and male breast cancer patients were created. Each MBC was matched with a female counterpart (FBC) that showed accordance in at least 5-7 tumor characteristics (age, TNM, grade, hormone receptors, HER2 stage).&#x2028; Results:&#x2028; FBC and MBC (n=113 patients each) were evaluable for this analysis. For MBC the following tumor characteristics were documented: &gt;60% advanced stages (T2-4), only 6% well differentiated, 42.5% nodal-positive, 86% hormone-sensitive (ER-positive 79.2%, PR-positive 76.9%), 6.2% HER2 positive.&#x2028; 83.2% of MBC had a mastectomy/axillary dissection (FBC 49.0%), 55% adjuvant radiotherapy (FBC 66.7%), 64% adjuvant systemic therapy (FBC 80.6%), 32.7% chemotherapy (FBC 49.5%) and 47.8% endocrine treatment (FBC 60.1%). 31% of MBC had a relapse (FBC 25.9%), 68.1% overall survival (OS) (FBC 70.4%), 98 months (FBC 76 months) median survival time. In univariate analyses reduced OS of MBC was significant associated with advanced tumor stages (p&lt;.005), poor histological grade (p&lt;.05), receptor negative (p&lt;.05) and nodal-positive tumors (p&lt;.05). Furthermore adjuvant radiotherapy showed survival benefit. However, in multivariate analysis only tumor stage showed statistical significance (p&lt;.01). Regarding these tumor characteristics no OS differences could be observed between FBC and MBC. However, MBC showed a trend to a shortened survival for receptor negative tumors in comparison to FBC (p=.055).&#x2028; Discussion:&#x2028; 1. Delayed diagnosis of MBC; 2. Our study showed more advanced and undifferentiated tumors with a high percentage of nodal positivity; 3. In our analysis these unfavorable tumor characteristics were not related to a poor OS; 4. We found no significant differences regarding disease outcome between FBC and MBC; despite of a more aggressive adjuvant treatment for FBC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4129.
Local-regional and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies.
Authors: Yi M , Hunt KK , Meric-Bernstam F , Kronowitz SJ , Nayeemuddin KM , Feig B , Hwang RF , Symmans W , Lucci A , Ross MI , Ames FC , Bedrosian I , Singletary E , Kuerer HM 
Published: December 2010

Abstract
Abstract #4138
Background: Although skin-sparing mastectomies (SSMs) are becoming more common, there are few data regarding the local-regional and distant recurrence rates. The aim of this study was to examine the incidence of local-regional recurrence, distant recurrence, and survival in breast cancer patients who underwent SSMs or non-skin-sparing mastectomies (NSSMs) at our institution.&#x2028; Methods: We reviewed records of patients with primary breast carcinoma stage 0 to III who underwent total mastectomies with or without complete axillary dissection at our center from January 2000 to December 2005. After excluding patients with bilateral breast cancer, mastectomies for recurrent breast cancer, and patients with less than two-year follow-up, there were 1623 patients for study. Patient and tumor characteristics were evaluated and comparisons undertaken between the SSM and NSSM groups with univariate and multivariate logistic analyses. Kaplan-Meier curves and log-rank test were used to evaluate the overall and disease-free survival in the two groups.&#x2028; RESULTS: Of the 1623 patients, 465 (28.7%) patients underwent SSM and 1158 (71.3%) underwent NSSM. Patients who underwent NSSM were older (55.6 vs. 48.9, p&lt;0.0001) and had more advanced stage tumor (stage II or high: 48.3% vs. 28%, p&lt;0.0001). Significantly more patients in the NSSM group received systemic chemotherapy (p=0.045), radiation therapy (p&lt;0.0001), and endocrine therapy (p=0.002). At a median follow-up of 24.4 months (range 1.1-95.3), 138 patients (4.6%) had local-regional or distant recurrence. Specifically, 7 patients (1.5%) in the SSM group and 34 patients (2.9%) in the NSSM group had local-regional recurrences (p=0.097). The distant recurrence rate in patients undergoing SSM or NSSM was 14 (3.0%) and 110 (9.5%) patients (p&lt;0.0001) at median follow-up time of 29.2 and 25.4 months, respectively. There is no difference in disease-free survival between the SSM group and NSSM after adjusting for tumor TNM stage and final nodal status at a median follow-up time of 54.3 months and 53.2 months, respectively.&#x2028; CONCLUSIONS: SSM is safe and effective in appropriately selected patients with breast carcinoma.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4138.
Fibrin sealant for the prevention of axillary seroma formation after axillary lymph node disection. A prospective randomized study.
Authors: Sanchez-Mendez JI , Lopez-Rodriguez MJ , Sanchez-Martinez C , Martinez-Garcia MT , Iniesta Doñate MD , Ordas Santotomas J 
Published: December 2010

Abstract
Abstract #4139
Background&#x2028; The most frequent postoperative complication after axillary limph node dissection is the axilary seroma (AS) formation. Currently accepted practice includes insertion of one or more drainage system for fluid evacuation. Several methods have been proposed to decrease AS formation, such as closed suction catheters, shoulder immobilisation, tetracycline sclerotherapy, talc podrage and closure of dead space; however no of them have reduced the incidence of AS. Seromas are associated with wound infection, wound dehiscence and skip flap necrosis, which prolong the recovery and can extend patient´s stay in Hospital.&#x2028; The aim of this prospective randomized controlled trial was to evaluate the efficacy of fibrin sealant (FS) on the prevention of AS.&#x2028; Material and Methods&#x2028; Sixty-two patients undergoing axillary lymph node dissection were randomized to treatment with drainaje alone (arm A, n=49), drainage plus FS (arm B, n=12), or FS alone (arm C, n=53). Arm B was cancelled after primary results. Efficacy was evaluated in terms of lengh of hospital stay, volumen of fluid drainage and rate of wound related complications (seroma, hematoma, infection, dehiscence) in each arm.&#x2028; Results&#x2028; No significative differences are detected neither type of surgery, nor histlogycal characteristics.&#x2028; &#x2028; The mean result is a difference of almost minus 3 days in postoperative stay in the FS group.&#x2028; &#x2028; Conclusions&#x2028; 1- Application of fibrin sealant reduces the amount of serosanguinous drainage and the length of postoperative stay in patients who have undergone axillary lymph node dissection.&#x2028; 2- Fibrin sealant allows to avoid the insertion of an axillar drainage system&#x2028; 3- It is very important the correct preparation and application of the fibrin sealant and it should be performed by a qualified surgeon.&#x2028; 4- Future clinical trials toasses the role of fibrin sealant seroma are warranted.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4139.
Complications of methylene blue dye infiltration for sentinel lymph node biopsy in breast cancer.
Authors: Piscatelli N , Crawford S , Larkin A , Robert Q , Layeequr Rahman R 
Published: December 2010

Abstract
Abstract #4140
Background: Isosulfan blue has proven invaluable for sentinel lymph node identification in breast cancer. However, an intermittent supply shortage of this agent over the last few years has led to alternative usage of methylene blue. Worldwide, methylene blue is traditionally viewed as a less expensive and safer equivalent to isosulfan, with few reports of significant side effects. Its increased usage has led to anecdotal reports of local skin reactions. This study serves to review the rate of local complications observed following subareolar infiltration of methylene blue for sentinel lymph node identification in breast cancer staging.&#x2028; Material Methods: This is a retrospective review of prospectively collected data in a university based surgical oncology practice. Records of all patients undergoing sentinel lymph node biopsy for breast cancer between August, 2007 and April, 2008 were reviewed (the switch from Isosulfan to Methylene blue was made in August of 2007). Local complication of fat necrosis was recorded. Tumor stage, neoadjuvant therapy, volume and dilution of dye used were analysed for association with fat necrosis.&#x2028; Results: One hundred and three patients underwent sentinel node biopsy for breast cancer during the study period. Seven (7%) patients developed fat necrosis at the site of injection. The rate of injection site fat necrosis is associated with the volume of methylene blue [0% for &lt;3cc and 7.2% for &gt; 3cc (p = 0.0071)]; there was no association with tumor stage [3.2% for stage &lt;1, 13.1% for stage 2 and 0% for stage 3 (p=0.343)] and tumor type [7.3% for invasive ductal cancer, 8.3% for invasive lobular and 0% for in situ cancer (p=1.000)].&#x2028; Discussion: While methylene blue has typically been viewed as an inert agent for sentinel node biopsy, our study documents a 7% rate of fat necrosis. This is clinically significant in terms of painful symptoms and also the work-up that it may necessitate as a new mass in a breast cancer patient which has suspicious appearance on traditional imaging studies.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4140.
Lipomodelling of the breast.
Authors: ELFadl D , Mahapatra T , McManus P , Drew P 
Published: December 2010

Abstract
Abstract #4149
Background: Lipomodelling is the autologous transfer of fat to correct congenital and post-surgical deformities. Recent improvements in technique have provided the opportunity for a greater volume of fat transfer thus increasing its potential application following surgery for benign and malignant breast disease.&#x2028; Materials & methods: After injecting a solution of local anaesthetic, normal saline and 1:106 adrenaline into donor sites in the abdomen and thighs, fat was aspirated with 3mm cannulae and centrifuged for 5 minutes. The fat was then re-injected into pre-marked areas in the breast using a 3mm injection cannula. Patients were followed up in a specialist breast clinic.&#x2028; Results: 23 patients (22 female, 1 male) were treated between November 2007 and May 2008. The mean age was 50.6 years (36-61).&#x2028; &#x2028; Prior to lipomodelling, volume deficit was observed in all patients. A visible depression was identified in 43.5% (n=10), significant flap atrophy in 21.7% (n=5), skin tethering in 21.7% (n=5) and implant rippling in 13% (n=3). Ten patients (43.5%) required lipomodelling to the upper pole, while in 7 patients (30.4%), the location was closely associated with the surgical scar.&#x2028; The average volume of fat harvested was 210.7 ml (85-510), and that injected per breast was 107.1 ml (45-206). Injections were stopped when slight overfilling was observed. Excessive tissue tension was avoided. Operative time varied between 45-100 minutes.&#x2028; During the first follow up visit, satisfactory results were recorded. 3 patients were booked for their second operation.&#x2028; Nine patients were seen at 3-4 months (second follow up visit). Two patients had clinical and radiological evidence of fat necrosis. One patient had marked volume resorption and numbness at the donor site. Eight patients had good volume retention. Two patients were booked for further lipomodelling at this stage.&#x2028; One patient had further lipomodelling five months after the first session, with satisfactory results, and is awaiting a third session.&#x2028; &#x2028; Discussion: Early results have shown satisfactory cosmetic outcome and patient satisfaction. The technical simplicity and autologous nature make lipomodelling an attractive option to both surgeon and patient. However it is not universally successful and further follow-up is required before the long term effects of the technique in cancer patients can be confirmed.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4149.
A new enrichment model for high sensitivity detection and downstream analyses of circulating tumor cells in breast cancer patients.
Authors: Deng G , Mishaeli M , Miller M , Zayed AA , Huntsman D , Gelmon K , Yerushalmi R , Manna E , Krag D , Habib I , Williamson J , Burke J 
Published: December 2010

Abstract
Abstract #4162
The detection of circulating tumor cells (CTCs) in breast cancer patients have the potential to improve prognostication and the monitoring of response to treatment. Most CTC enrichment technologies are based on binding to anti-EpCAM antibodies. The sensitivity of such assays is limited by tumors that express no or undetectable levels of EpCAM. Improvements in CTC detection coupled with the development of systems to interrogate CTCs for therapeutic target expression could lead to novel applications for patient monitoring, clinical diagnosis and treatment. In this study, we describe a sensitive and reproducible enrichment method for CTCs. We defined cells as circulating tumor cells with three criteria: Positive for cytokeratin (CK+) and DAPI (nuclear) (DAPI+) and negative staining for CD45 (CD45-). We have previously reported that this system has a higher sensitivity for circulating tumor cell detection and provides a better platform for CTC downstream analyses compare to the methods currently available in the market. Herein, we describe the use of this platform for the evaluation of breast cancer biomarkers in CTCs. Blood samples from patients with metastatic breast cancer were used for CellSearch™ assay (Veridex , LLC ) and our CTC assay (A1000 CTC enrichment and detection kit, Genetix). We performed the CTC enrichment assay using the combination of anti-CK and anti-EpCAM antibodies. CTCs were identified with brightfield and fluorescence labeled anti-CK, anti-CD45 and DAPI (nuclear stain) images. The Ariol® system (Applied Imaging Corporation) was employed for automated cell image capture and analysis of CTCs on glass slides. CTCs enriched on the glass slides were used for CTC downstream analysis. Our CTC enrichment model is designed to have the capability to enrich all the three types of CTCs including CK+ & EpCAM+, CK+ & EpCAM-/low and CK-/low & EpCAM+ cells. Compared to the enrichment methods using anti-EpCAM or anti-cytokeratin antibody alone, a higher CTC detection rate and a larger dynamic CTC detected range were obtained with our new enrichment model. Interestingly there were clear CTC number differences with enrichment methods in the higher CTC count patient samples which indicate that the different enrichment methods may enrich different types of CTCs from patient blood samples.&#x2028; Results of DNA and RNA FISH analyses on enriched CTCs indicate that the CTCs on glass slides can be used for its downstream analyses directly or indirectly. Our method may have better performance on enrichment of heterogeneous CTCs and provide a better platform for CTCs profiling for biomarker evaluations and CTC downstream analyses.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4162.
MM-111: a novel bispecific antibody targeting ErbB3 with potent anti-tumor activity in ErbB2 over-expressing malignancies.
Authors: Nielsen U , Huhalov A , Harms B , Paragas V , Adams S , Gu J , Nguyen S , Luus L , Oyama S , Razlog M , Overland R , Wallace M , Kohli N , Feldhaus M , Schoeberl B , McDonagh C 
Published: December 2010

Abstract
Abstract #4166
ErbB3 has been identified as a preferred dimerization partner of ErbB2, critical for driving the proliferation of ErbB2 over-expressing breast tumors. We have designed a bispecific antibody, MM-111, which inhibits ligand-induced phosphorylation of ErbB3 with sub-nanomolar potency by exploiting the abundant expression of its dimerization partner, ErbB2, for specific targeting to cancer cells that express both receptors. We employed computational physicochemical modeling to guide the kinetic optimization of the monovalent binding affinities to the ErbB2 and ErbB3 receptors to increase the potency and specificity of MM-111 for tumor cells. We have demonstrated that MM-111 inhibits activation of the phosphatidylinositol 3-kinase pathway in vitro and in vivo, resulting in attenuation of tumor proliferation. Inhibition of growth by MM-111 has been observed in several murine xenograft models including BT474 and MDA-MB-361 breast tumors. While the antitumor activity of MM-111 is positively correlated with ErbB2 expression levels, MM-111's potent inhibition of ErbB3 phosphorylation and signaling downstream from this receptor differs markedly from currently available therapies targeting ErbB2 over-expressing breast tumors and thus provides a novel approach to treatment for these malignancies. In conclusion, our data demonstrate that the combination of computational biology with antibody engineering has resulted in the development of a promising, novel therapeutic, MM-111, that has potent antitumor activity in malignancies driven by the ErbB2/3 oncogenic unit.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4166.