bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Androgen Receptor in Breast Cancer.
Authors: Park S. , Park H. , Choi S. , Lee J. , Park B. , Lee K. 
Published: December 2010

Abstract
Background: Androgen receptor (AR) is one of biomarkers and its role in breast cancer is still unclear. The aim of this study was to investigate the relationship between AR expression and clinicopathological factors in breast cancer patients.Patients and Methods: AR was consecutively evaluated in 413 primary breast cancers from whole sections of surgically resected specimens using immunohistochemical staining from January 2008 to March 2009. The associations between AR expression and clinicopathological parameters were analyzed. Tumors with 10% or more nuclear stained cells were considered as positive for AR expression. The differences between variables were calculated by chi-square test and Fisher's exact test was used when appropriate.Results: The median age at diagnosis was 49 years (range, 26-84). AR was found in 72.7% (48/66) of in-situ carcinoma and in 72.9% (253/347) of invasive carcinoma. Overall expression rates of AR were 72.9%, which were higher than those of ER and PR expression, 68.5% and 62.0%, respectively. AR was significantly expressed in patients with no elevated preoperative serum cancer antigen 15-3 (CA 15-3) levels (p = .042), smaller tumor size (p = .035), lower histologic grade (p &lt; .001), ER-positive (p &lt; .001), progesterone receptor-positive (p &lt; .001), and non-triple-negative breast cancer (p &lt; .001). Metaplastic, medullary, and mucinous types carcinomas showed less AR expression (p = .030). Although it was statistically not significant, patients with younger age (≤ 35 years), axillary lymph node involvements, and higher stage showed higher rates of AR negativity. In ER-negative tumors, AR expression was significantly correlated with HER-2 over-expression (p &lt; .001). In ER-positive tumors, however, there was no relationship between AR expression and HER-2 over-expression (p &gt; .05).Conclusions: AR is expressed in a significant number of breast cancers and is associated with favorable tumor differentiation and smaller tumor size. These results might suggest that AR may be an independent prognostic factor in breast cancer. AR may also be associated with growth factor signaling and be useful therapeutic target in ER-negative tumors.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4156.
Tumor Volume Analysis and Tumor Doubling.
Authors: Gordon A. , Stebbing J. , Shousha M. , Coombes R. 
Published: December 2010

Abstract
Background: Volume is the most sensitive and accurate parameter to assess tumor response to treatment. We have proposed that data be expressed as volume in cubic centimetres TVA (Tumor Volume Analysis)1. When we applied TVA to a breast cancer trial and converted the data from diameter centimetres to volume in cubic centimetres the differences were statistically signifcant2.Three dimensional measurements: Volume measurements are most accurate if all three dimensions are measured to record any asymmetric growth[ref]. In Table 1 diameter permutations are shown of a 3cm mass together with percentage changes in each example. This demonstrates the extent that changes in the lesser two axes of a mass affect tumor volume. Accurate 3D volume measurement is essential to estimate tumor doubling.Tumor Doubling and Redoubling: Tumor doubling for a carcinoma is quoted as under 177 days [ref] or under 500 days[ref]. With a mean of 100 days[ref] or 117 days[ref]. Much of the work has been carried out on metastatic pulmonary nodules of various tumors. An early paper did quote doubling times as by diameter and provided a graph to convert data into volume8. A calculator has been described and patented to provide these functions2.Tumor Doubling Time (TDT): Tumor doubling can be regarded as an increase in volume over a unit of time[8, ref]. We propose this TDT be quantified with the period of growth expressed in days for example TDT 120 implies a tumor doubling time of 120 days. A formula that does allow for exponential growth assuming a constant growth is as follows: TDT = D x log(2)/log(1+ r/100). Where TDT = tumor doubling time; D = interval in DAYS between volume measurements; r = rate of growth; r/100 = (Vol 2-Vol 1)/Vol 1 x 100%. This option for measuring tumor doubling can be added as a fourth and further facility to the calculator already described [Patent PCT/GB07/003526]2Conclusions: 1. Tumor doubling is qualified by volume changes in cm3. Tumor doubling time (TDT) in days quantifies tumor doubling. 2. Measurement of TDT can be made as an extra facility on the calculator already described. The calculator can be used to estimate TDT using two measured volumes and the interval in days. 3. A similar formula can also be used to measure downsizing in response to neoadjuvant therapy as complete response time (CRT).References:1. SABCS 2007 Poster # 2021Tumor Volume Analysis. A better way than RECIST? [A B Gordon, J Stebbing, R C Coombes]2. SABCS 2008 Poster # 4023 Tumor Volume Analysis in Clinical Oncology. [A B Gordon, J Stebbing, R C Coombes] 8. V P Collins et al. Observations on Growth Rates of Human Tumours. American Journal of Roentgenology. V. 76 p. 988-1000 1956Table 1. Volume Calculation of Three Dimensional MassSHAPE SphereOne Diameter3x3x3cm14.14cm3100%TangerineTwo Diameters3x3x2cm9.42cm367%EggTwo Diameters3x2x2cm6.28cm344%CigarTwo Diameters3x1x1cm1.57cm311%DateThree Diameters3x2x1cm3.14cm322%
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5030.
Bilateral Breast Cancer: Analysis of Incidence, Characteristics and Outcome of the Disease.
Authors: Kheirelseid E. , Jumastapha H. , Miller N. , Curran C. , Sweeney K. , Newell J. , Kerin M. 
Published: December 2010

Abstract
Background: Despite the widespread adoption of breast conservation therapy in breast cancer, there is a dramatic increase in the rate of bilateral mastectomy in USA. The aim of this study was to address the incidence of bilateral breast cancer (BBC) and to investigate its characteristics, survival and outcome compared to unilateral breast cancer.Methods: Data was acquired from the prospectively maintained NUI Galway breast cancer database between 1988 and 2008. BBC were then categorized as synchronous (within 12 months) or metachronous cancer (after 12 months of first tumour). SPSS was used for data analysis.Results: The incidence of bilateral breast cancer in our population was 4.4% (112 of 2524). Of those 2.1% were synchronous while 2.3% were metachronous. Compared to unilateral cases, bilateral cancer patients were younger (0=0.021) and had smaller size (p=0.001) and earlier stage (p&lt;0.001) tumours at diagnosis. There were no differences in histological type (p=0.630) and grade (p=0.054)). While there was no significant difference in survival for patients with bilateral compared to unilateral tumour (p&gt;0.05), the synchronous bilateral tumour was associated with poor overall survival (p=0.010) and disease free survival (p=0.013) in comparison to metachronous bilateral tumour.Conclusion: We observed significant differences in bilateral tumour characteristics compared to unilateral disease. Although bilateral synchronous tumour was associated with poor outcome and overall survival, patients with metachronous disease do as well as patients with unilateral tumour. The increasing practice of bilateral mastectomy is not supported by this large single centre experience.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5033.
Use of BIBW 2992, a Novel Irreversible EGFR/HER1 and HER2 Tyrosine Kinase Inhibitor To Treat Patients with HER2-Positive Metastatic Breast Cancer after Failure of Treatment with Trastuzumab.
Authors: Hickish T. , Wheatley D. , Lin N. , Carey L. , Houston S. , Mendelson D. , Solca F. , Uttenreuther-Fischer M. , Jones H. , Winer E. 
Published: December 2010

Abstract
Background: BIBW 2992 (Tovok™*) is a novel, oral, irreversible inhibitor of the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER)1 and HER2 inhibitor, with preclinical activity in trastuzumab-resistant cell lines overexpressing HER2 and Phase I clinical activity. A Phase II study of BIBW 2992 in patients with HER2-positive breast cancer who have progressed following treatment with trastuzumab was conducted in the US and the UK.Methods: A multi-institutional, open-label, single-arm Phase II study was conducted. Eligible patients had stage IIIB or IV HER2-positive metastatic breast cancer, with progression following trastuzumab treatment or intolerance of trastuzumab, received no prior EGFR-targeted therapy, had measurable disease, Eastern Cooperative Oncology Group performance status of 0–2 and adequate organ function. Patients received 50 mg BIBW 2992 once-daily until disease progression. Tumor assessments were performed every two treatment courses (one course is 28 days). The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors). Safety data were also collected.Results: A total of 41 patients started treatment on the trial. Patients had received a median of three lines of prior therapy (range, 0–15). Thirty-four patients are evaluable for response. Of these, four patients had a partial response (PR) and eight patients had stable disease maintained for at least four cycles. One patient with confirmed PR remained on treatment until progression at 63 weeks. The most frequently observed side-effects to date are rash (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 in four patients [9.8%]) and diarrhea (CTCAE Grade 3) in nine patients. There have been 21 dose reductions in 18 patients.Conclusion: BIBW 2992 was safe and induced promising early clinical responses in HER2-positive breast cancer patients who have progressed following treatment with trastuzumab. Manageable cutaneous adverse events and diarrhea were the main side-effects.*Trade name not FDA approved.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5060.
Addition of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) to Trastuzumab Stabilizes Disease in Patients with Trastuzumab-Resistant, HER2+ Metastatic Breast Cancer.
Authors: Cheng Y. , Cheng Y. , Valero V. , Davis M. , Hortobagyi G. , Ueno N. , Ueno N. 
Published: December 2010

Abstract
Introduction: Trastuzumab with or without chemotherapy is the standard of care for patients with HER2+ metastatic breast cancer. The proposed mechanism of trastuzumab-induced regression of HER2+ tumors includes inhibition of tumor cell proliferation, potentiation of chemotherapy, and facilitation of immune function through antibody-dependent cell-mediated cytotoxicity. GM-CSF (Leukine) is a cytokine that mediates antibody-dependent cell-mediated cytotoxicity. We studied the feasibility and efficacy of adding GM-CSF to trastuzumab in patients with trastuzumab-resistant, HER2+ metastatic breast cancer.Patients and Methods: Patients with measurable, HER2+ metastatic breast cancer that progressed after treatment with trastuzumab with or without chemotherapy were continued on trastuzumab alone at 2 mg/kg intravenous weekly. GM-CSF (250 μg/m2 subcutaneous daily) was added until the absolute neutrophil count (ANC) was greater than 10,000/mm3, then given every other day while the ANC was maintained below 10,000/mm3. Disease was restaged every 8 weeks. Treatment with trastuzumab and GM-CSF was continued until disease progression or intolerable toxicity.Results: Of 18 eligible patients with progressive HER2+ metastatic breast cancer, 17 (median age 48 yr, range 27–75 yr) were evaluable. Nine had hormone receptor–positive disease. The median number of metastatic sites was 2 (range 1–3); the most common site was the liver (n=10). The median number of prior regimens (trastuzumab with or without chemotherapy) for metastatic disease was 2 (range 1–5). One patient developed rapidly progressive disease 2 weeks after the start of study therapy and died soon after. The other 16 patients continued treatment until disease progression. No disease response was observed, but 5 patients (29%) had stable disease with a median duration of 15.8 weeks (range 10–53.9 weeks). Thirteen patients had grade 1 toxic effects; 6 patients, grade 2; and 2 patients, grade 3 (fatigue and muscle aches). The most common toxic effect was rash at the injection site, followed by skin rash, fatigue, and muscle aches. No grade 4 or irreversible toxic effect was seen.Conclusion: The addition of GM-CSF to trastuzumab alone in patients with trastuzumab-resistant, HER2+ metastatic breast cancer stabilizes the disease for a median duration of 15.8 weeks without causing any significant toxic effects in 29% of heavily pretreated patients. Its administration is simple, safe, and feasible. This regimen, trastuzumab and GM-CSF, needs further evaluation in combination with chemotherapy or other biological agents.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5103.
In Vivo Activity of ARRY-380, a Potent, Small Molecule Inhibitor of ErbB2 in Combination with Trastuzumab, Docetaxel or Bevacizumab.
Authors: Lee P. , Anderson D. , Bouhana K. , Garrus J. , Napier C. , Avrustkaya A. , White A. , Pheneger T. , Winkler J. 
Published: December 2010

Abstract
ARRY-380 is an orally active, potent small molecule tyrosine kinase inhibitor targeting ErbB2. The compound is a reversible, ATP-competitive inhibitor with nanomolar potency against ErbB2 in both in vitro and in cell-based assays. This compound has very good in vivo and in vitro PK/ADME properties and has shown excellent activity in numerous mouse tumor models including breast (BT-474, MDA-MB-453), ovarian (SKOV-3) and gastric (N87) carcinoma models. Here we demonstrate excellent single agent activity and combinability with trastuzumab, docetaxel or bevacizumab in breast and ovarian carcinoma models. For the BT-474 studies, female SCID beige mice were implanted with tumor fragments. For the SKOV-3 tumor studies, female nude mice were inoculated with cells subcutaneously in the flank. Animals received: doses of ARRY-380 ranging up to 200 mg/kg/d, PO; and/or trastuzumab at 20 mg/kg, IP, Q3D or QW; and/or docetaxel at 10 mg/kg, IV, Q3D; and/or bevacizumab at 10 mg/kg, IP, Q4D x3. Tumor size was measured at regular intervals and subsets of animals were monitored for up to 90 days to determine tumor-free survival. In the BT-474 model, ARRY-380 demonstrated significant dose-related tumor growth inhibition (TGI; 50% at 50 mg/kg/d and 96% at 100 mg/kg/d) with numerous partial regressions (&gt;50% reduction from baseline size) at the higher dose level in 9/12 animals. One complete response was observed at the higher dose. Trastuzumab alone provided a 45% TGI with no regressions. ARRY-380 (50 mg/kg/d) in combination with trastuzumab showed a 98% TGI with complete regressions in 9/12 animals and two partial regressions. At dose of 100 mg/kg/d of ARRY-380 in combination with trastuzumab, there was 100% TGI and all animals had complete responses. Docetaxel as a single agent produced a 55% TGI with no regressions. In combination with ARRY-380 (50 mg/kg/d), there was an 81% TGI and five partial regressions. In the SKOV-3 model, ARRY-380 demonstrated significant dose-related tumor growth inhibition (TGI; 39% at 50 mg/kg, BID and 96% at 100 mg/kg, BID) with partial regressions (&gt;50% reduction from baseline size) at the higher dose level in all animals. Bevacizumab alone provided a 55% TGI with no regressions. ARRY-380 (50 mg/kg, BID) in combination with bevacizumab showed 80% TGI with partial responses in 7/8 animals and one stable disease. From this work we have demonstrated superb single agent activity for ARRY-380 in the BT-474 human breast carcinoma xenograft model and the SKOV-3 human ovarian carcinoma model. In addition, ARRY-380 has shown additive activity and tolerability with trastuzumab, docetaxel and bevacizumab. ARRY-380 has entered Phase I clinical trials in patients with advanced cancers.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5104.
Evaluation of Factors Associated with Recruitment in Breast Cancer Clinical Trials in a Specialized Breast Cancer Centre.
Authors: Lemieux J. , Forget G. , Brochu O. , Camden S. , Provencher L. , Robert J. , Cantin G. , Desbiens C. , Doyle C. , Morin J. , Poirier B. 
Published: December 2010

Abstract
Background: Recruitment of patients (pts) in cancer clinical trials has been reported to be between 3-5%. Very few data come from Canada. Methods: The objective was to measure the recruitment and its associated characteristics in breast cancer clinical trials for non-metastatic breast cancer pts. This was a retrospective cohort study at the Centre des Maladies du Sein Deschênes-Fabia, a specialized breast cancer centre in Québec City, Canada. Clinical trials opened between 2004 and 2008 were used. For each protocol, main criteria were used to define the population under study (e.g. triple negative breast cancer). Charts were identified from our database and reviewed in decreasing chronological order of diagnosis. Staging, hormone receptors status and Her2 status were available from the database. All charts were reviewed to assess eligibility criteria (inclusion and exclusion criteria). Also, information was sought in the notes about whether or not the protocol has been proposed to the pt, if the pt accepted and if not, reason(s) for refusal. Protocol and physicians characteristics were collected. Results: A total of 9 protocols were studied and 244 charts identified (relates to 704 pt-protocols because one pt could be assessed for more than one protocol if applicable). Eligibility could not be assessed for 19% (n=138) pt-protocols. Among all pt-protocols, 74.4% met all the eligibility criteria. There was a note in the chart, about protocol being proposed to a potentially eligible pt, in 13.8% of the pt-protocols. Overall, 9.7% of pt-protocols were recruited. Among patients who had a protocol offered, 74.2% accepted. Data on characteristics associated with recruitment will be presented at the meeting. Conclusion: Enrollment in clinical trials in a specialized breast cancer centre is slightly higher than the 3-5% generally reported but still low. Interventions should focus on finding ways to offer a clinical trial when available to every suitable eligible patient.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5122.
The Interaction of High Mobility Group Proteins with the p160 Coactivator SRC-1; a Role in Endocrine Resistance.
Authors: Redmond A. , Stafford A. , McIlroy M. , Hill A. , Young L. 
Published: December 2010

Abstract
Breast cancer affects one woman in ten in the western world and despite the phenomenal advances in recent years, the mortality rate still remains at around 35%. Resistance to current endocrine therapies, including tamoxifen and aromatase inhibitors, is common with recurrence of disease in 30-40% of patients. The estrogen receptor (ER) coactivator protein SRC-1 plays an important role in this resistance. We examined SRC-1 protein expression in a large cohort of breast cancer patients (n=560) and found expression to be a strong predictor of disease recurrence in patients treated with adjuvant tamoxifen (hazard ratio: 5.032, p&lt;0.0001). Identification of SRC-1 interacting proteins will provide key insights into the role of SRC-1 in the development of tumour recurrence. We employed a mass spectrometry-based screen to identify proteins which could differentially interact with SRC-1 in endocrine resistant compared with endocrine sensitive breast cancer cells. Selected SRC-1 interacting proteins relevant to endocrine resistance include the high mobility proteins HMGB1 and HMGB2, which have previously been reported to enhance binding of the estrogen receptor to its response elements in target gene promoters. Immunoprecipitation assays confirmed increased interactions between HMGB2 and SRC-1 following treatment of the endocrine resistant cell line LY2 with tamoxifen and estrogen. Steroid treatment also increased trafficking of the coactivator and the SRC-1 interacting protein to the nucleus of tumour epithelial cells. Treatment enhanced recruitment of SRC-1 to the promoter of the oncogene c-Myc and enhanced target gene expression. HMGB2 expression in the breast cancer patient TMA correlated with SRC-1 and poor disease-free survival. These findings would indicate an important role for HMGB2 in the development of endocrine resistance in breast cancer patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5138.
Prediction of Metastasis in Node-Negative, Hormone Receptor Positive, Tamoxifen Adjuvant Treated Primary Breast Cancer Patients Using Ki-67 (IHC) and RT-PCR Based 14-Gene Prognostic Signature.
Authors: Schlotter C. , Wassmann K. , Bosse U. , Kemming D. , Brandt B. , Vogt U. 
Published: December 2010

Abstract
Background: Risk estimation based on the recommendations of St. Gallen Consensus commonly decides for additional cytostatic therapy in node-negative (N-), hormone receptor positive (HR+) primary breast cancer patients. High proliferative activity in the HR+ subtype confers a 19-fold relative risk of relapse compared with HR+ tumors of low proliferative activity. Furthermore immunohistochemically determined Ki-67 is characterized as a Luminal B marker that identifies a high risk subgroup in HR+, N- breast cancer patients.Aim of this investigation was to compare risk estimation using Ki-67 (%) with the results of a RT-PCR based multi-gene prognostic signature. Methods: Tumor tissues of totally 321 unselected primary breast cancer patients were formalin fixed and routinely processed for immunohistochemical determination and scored for protein expression of ER, PgR and Ki-67. HER2 was determined using dd-PCR. Content of both hormone receptors and proliferation activity were evaluated counting positively coloured nuclei from at least 100 tumor cells. The median follow up was 61 months. To calculate the cut off for high proliferation Ki-67 values were subjected to a log rank CART analysis. High proliferation was defined by Ki-67 of 19% and more. With this cut off it was possible to distinguish significantly various patient cohorts (N-, pT1, postmenopausal) into two different risk groups regarding metastasis free survival. The definition of low risk was low proliferation and HER2 negativity, of high risk high proliferation or HER2 positivity. The risk for metastasis of 16 new primary breast cancer patients was estimated based on two surrogate risk groups and the multi-gene prognostic signature. Results: Tamoxifen adjuvant treated HR+, HER2-, low proliferating (Ki-67 &lt;19%), N- low risk patients (N= 68) and HR+, HER2-, high proliferating/HR+, HER2+, N- high risk patients (N= 84) showed a recurrence rate of 2.94% and 27.4%, respectively (P&lt; .000). In the ongoing observation study all 5 low proliferating HER2- tumors had a low risk gene prognostic signature. From 11 high proliferating HER2- patients one patient had a low risk gene signature (9%), 3 patients a moderate risk gene signature (27%) and 7 patients a high risk gene signature (64%). Conclusion: Despite the small number of patients investigated up to now (N= 16) the preliminary results appear to show that low proliferative activity is associated with a low risk gene prognostic signature, whereas high proliferation means only in part a high risk gene prognostic signature.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6025.