bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers associated with pathologic complete response to neoadjuvant chemotherapy in women with locally advanced breast cancer: results from the I-SPY TRIAL (CALGB 150007/150012 & ACRIN 6657).
Authors: Livasy C , Carey L , DiMichelle A , Cowan D , Little D , Markey J , Moore D , Investigators I-SPY Clinical , Dressler L 
Published: December 2010

Abstract
Abstract #5102
Background: The I-SPY trial is a multi-institutional study of locally advanced breast cancers in which serial biopsies of breast tumors are performed at multiple timepoints, allowing comparison of tumor biomarker status pretreatment, during treatment, and after treatment. The primary objective is to identify markers of response to neoadjuvant chemotherapy. The aim of this study was to identify immunohistochemical biomarkers associated with pathologic complete response (pCR).&#x2028; Methods: Eligible patients had biopsy-confirmed primary breast cancer measuring at least 3 cm. Required initial treatment was an anthracycline based neoadjuvant chemotherapy regimen: AC followed by T (91%), AC without T (6%), and chemotherapy beyond AC +/- T 2%. Immunohistochemistry (IHC) for HER2, EGFR, p53, Bcl2 and Ki-67 was performed centrally on core samples at baseline. Estrogen receptor and progesterone receptor results were obtained from each institution. Proxy IHC tumor subtypes were defined as follows: luminal A (ER or PR+/HER2-), luminal B (ER or PR+/HER2+), basal-like (ER-/PR-/HER2-), and HER2 (ER-/PR-/HER2+). Following completion of chemotherapy, post-surgical excision/mastectomy cases were reviewed centrally to determine residual cancer burden including pCR rate.&#x2028; Results: 221 patients were enrolled and completed therapy. The median age was 49 years, with a range of 27-69. Median tumor size was 6 cm; 58% had clinically positive nodes. The positive rate for each biomarker was as follows: ER+ (57%), PR+ (47%), HER2+ (23%), EGFR+ (14%), p53+ (44%), Bcl2+ (49%), Ki-67 index ≥25% (38%), Ki-67 index ≥10% but &lt;25% (34%), and Ki-67 index &lt;10% (27%). The pCR rates based on biomarkers results are shown in the table below.&#x2028; &#x2028; Conclusion:&#x2028; For patients with locally advanced breast cancer, pCR to neoadjuvant chemotherapy was associated with tumor HER2 overexpression, hormone receptor-negative status, high Ki-67 index, EGFR expression, and absence of Bcl2 expression. Luminal A tumors, defined by IHC proxy, showed a very low pCR rate following neoadjuvant chemotherapy.&#x2028; Support: CALGB CA31964 and CA33601, ACRIN U01 CA079778 and CA080098, NCI SPORE CA58207.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5102.
Weekly paclitaxel improved pathological response of primary chemotherapy compared with standard 3 weeks schedule.
Authors: Ouyang T , Li J , Xie Y , Lu A , Li B 
Published: December 2010

Abstract
Abstract #5109
Background: Weekly paclitaxel is superior to every-3-wk schedule in the management of MBC. This single institute, prospective randomized trial was designed to compare the efficacy of the weekly paclitaxel to every-3-wk schedule in terms of pathological response.&#x2028; Material and methods: Histologically confirmed T1-3 N0-1M0 invasive breast cancer pts planed to receive adjuvant chemotherapy were eligible. After the completion of 2 cycles of CTFci ( CTX 500mg/m2 d1/d8, pirarubicin 35 mg/m2 d1/d8, 5-Fu 200 mg/m2.day.ci d1-28, every 4 weeks) primary chemotherapy, pts were randomized to received 4 cycles of PTq3w (arm A: carboplatin AUC 6mg/ml.min day1, paclitaxel 175mg/m2 day1, every 3 weeks) or PTq1w (arm B: carboplatin AUC 6mg/ml.min day1, paclitaxel 60mg/m2 day1/8/15, every 3 weeks) before surgery, stratified by clinical response to 2 cycles of CTFci. Status of axillary node were determined by sentinel node biopsy or ultrasound guided FNA (if abnormal ultrasonographically) before primary chemotherapy. Pathological response of the primary tumor was evaluated by using Miller and Payne system, clinical response was determined by ultrasonography.&#x2028; Results: From 05/2005 to 10/2007, 220 pts ( 196 were planed) under 65yr entered in this trial. 201 pts completed planed treatment and 12 pts(arm A 4 pts, arm B 8 pts)choice to have surgery after 2 cycles of paclitaxel treatment, other 7 pts (5 protocol violation, 1 without surgery, 1 treated in other hospital) were excluded for analysis. Clinical tumor status, node status, estrogen receptor expression, Her-2 expression and clinical response to CTFci were no different between two arms.&#x2028; &#x2028; Arm A resulted more G1/G2(loss of tumor cells less than 30%) and less G5/G4 ( loss of tumor cells more than 90%) than arm B (28.70% vs. 14.28% p=0.011, 44.44% vs. 58.10% p= 0.047 ). The pCR rate of positive node were 39.29%(11/28) in arm A and 54.17%(13/24) in arm B ( p=0.283).&#x2028; &#x2028; There were 17(15.74%) pts in arm A and 67(61.81%)pts in arm B experienced treatment delay caused by neutropenia(G3), thrombocytopenia(G2), anemia(G2) or hepatotoxicity(G2). There was no treatment related death.&#x2028; Conclusion: Weekly paclitaxel was well tolerant and more effective than 3 week schedule.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5109.
Changes in ER beta versus ER alpha in short-term studies of antiestrogen therapies.
Authors: Dzagnidze G , Robertson JF , Ellis I , Green A , Zhang H , Speirs V , Shaaban A , Garnett S , Lindemann J 
Published: December 2010

Abstract
Abstract #5113
Background: Fulvestrant (Faslodex™) is a novel estrogen receptor (ER) antagonist with no agonist effects used in the treatment of postmenopausal women with advanced breast cancer. Compared with other antiestrogen therapies, fulvestrant has a distinct and different mode of action; on binding to the ER it induces a rapid and dose-dependent degradation of ER alpha and concomitant decreases in progesterone receptor (PgR) levels and Ki67 labeling index (LI). The action of fulvestrant on ER beta is unknown and has been investigated in relation to other biomarkers in this study.&#x2028; Methods: This randomized, multicenter study included postmenopausal patients with previously untreated breast tumors (stage T1-T3) that were either ER+ or ER unknown. Patients were randomized to receive a single intramuscular dose of fulvestrant (50 mg [n=39], 125 mg [n=38], or 250 mg [n=44]), continuous daily tamoxifen (Nolvadex™) (20 mg/day [n=36]), or matching tamoxifen placebo (n=33) for 14–21 days prior to surgery. The effects of antiestrogen therapy on ER beta 1 and ER beta 2 levels and the relationship between these effects and changes in ER alpha, PgR and Ki67 LI were investigated. Effects on ER (alpha and beta) and PgR were determined by immunohistochemistry and expressed as mean percentage change from baseline H-score. Ki67 LI was determined as described previously1 and was expressed as median percentage change from baseline.&#x2028; Results: There was no overall treatment effect following placebo or antiestrogen therapy on ER beta 1 H-score (p=0.8537) or ER beta 2 H-score (p=0.5494). There were no significant differences between the individual fulvestrant dose groups, tamoxifen and placebo for mean changes in either ER beta 1 (50 mg: +34.8%, 125 mg: +42.8%, 250 mg: +15.5%; tamoxifen: +29.8%; placebo: +29.7%) or ER beta 2 (50 mg: +87.9%, 125 mg: +82.9%, 250 mg: +97.4%; tamoxifen: +98.1%; placebo: +64.2%). No correlations were observed between changes in ER beta 1 and changes in ER beta 2, nor between either ER beta 1 or 2 and ER alpha, PgR or Ki67 LI.&#x2028; Conclusion: Changes in ER beta did not correlate with fulvestrant dose (50 mg, 125 mg, or 250 mg) or other variables that have previously been shown to be related to fulvestrant activity. This study does not support the investigation of ER beta 1 or 2 as markers of the biological activity of fulvestrant high dose (500 mg/month) in ongoing trials such as FIRST and CONFIRM.&#x2028; 1Robertson et al. Cancer Res 2001; 61: 6739-6746.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5113.
Is the sentinel lymph node biopsy accurate for patients with initially clinically axilla-positive locally advanced breast cancer after neoadjuvant chemotherapy?.
Authors: Ozmen V , Muslumanoglu ME , Igci A , Canbay E , Ozcinar B , Mudun A , Eralp Y , Saip P , Tuzlali S , Dincer M , Dagoglu T , Kecer M , Parlak M 
Published: December 2010

Abstract
Abstract #5123
Background: Approximately one third of patients with locally advanced breast cancer (LABC) have no axillary metastatic lymph node(s) after neoadjuvant chemotherapy (NAC). Axillary dissection could be omitted in these patients if SLNB is negative. The aim of this study is to evaluate the accuracy of sentinel lymph node biopsy (SLNB) after NAC for LABC.&#x2028; Materials and Methods: Between January 1992 to May 2008, a total of 69 patients with clinical or radiological positive axilla (N1 or N2) in LABC were enrolled in this study. After NAC, all patients underwent SLNB followed by complete axillary lymph node dissection. SLNB was performed with either a combined detection using blue dye and radiocolloid or blue dye alone. All the sentinel lymph nodes were examined by multisection hematoxylin eosin staining and cytokeratin- immunohistochemistry, whereas the non-sentinel nodes were examined by routine histology.&#x2028; Results: Sentinel lymph nodes were successfully identified in 58 patients among 69 patients (85%). The median age was 46 (range 25 to 76). The clinical stages before chemotherapy were as follows: IIB:46%, IIIA: 22%, and IIIB: 32%, respectively. All of 58 patients had either clinically or radiologically suspicious node-positive disease based on ultrasound findings before neoadjuvant chemotherapy. Pathologic complete response were obtained in 5 patients (9%). The false negative rate was found to be 17.4 % (8/46), whereas the accuracy rate was 86.2% (50/58) among patients with succesful lymphatic mapping.&#x2028; Conclusion: The accuracy of the SLNB procedure seems to be not reliable in patients with locally advanced disease with a positive axilla before NAC therapy due to its high false negative rates. Therefore, complete axillary dissection is still required in patients with a positive-axilla before chemotherapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5123.
A randomised controlled trial to evaluate both the role and optimal fractionation of radiotherapy in the conservative management of early breast cancer.
Authors: Spooner D , Stocken DD , Jordan S , Bathers S , Dunn JA , Jevons C , Morrison M , Oates G , Grieve R 
Published: December 2010

Abstract
Abstract #5125
Background: Postoperative radiotherapy is routinely used in early breast cancer using 50Gy in 25 daily fractions (Long). Both the role of radiotherapy and shorter regimens require validation.&#x2028; Methods: Patients with clinical stage 1 and 2 disease were randomised to receive immediate postoperative (RT) or delayed salvage treatment (No RT). Patients receiving RT were further randomised to Long or Short (40Gy in 15 daily fractions) regimens. The primary outcome measure was time to first relapse. Reported results are at median follow up of 16.9 years (IQR 15.4 - 18.8).&#x2028; Results: 707 women were recruited between 1985 and 1992: median age 59 years (range 28-80), 72% post menopausal, median tumour size 2.0cms (range 0.12-8.0). 271 patients have relapsed: 110 RT, 161 No RT. Site of first relapse was reported as 158 (64%) locoregional and 87 (36%) distant. Immediate RT significantly reduced the risk of relapse by 42% (HR=0.58 (95%CI: 0.45, 0.73), chi2LR=20.40, p&lt;0.001) consistent across all prognostic subgroups. Immediate RT reduced the risk of locoregional relapse by 65% (HR=0.35 (95%CI: 0.25, 0.47), (chi2LR=40.47, p&lt;0.001). No difference in relapse site, or frequency was seen between the 2 fractions. No differences were seen in overall or breast cancer specific survival.&#x2028; Discussion: With a median follow-up of 17 years, this study confirms the benefit for patients with early breast cancer receiving radiotherapy. We conclude that a radiotherapy schedule of 40 Gy in 15 daily fractions is a safe, efficient and effective regime at least as good as the international conventional regime of 50 Gy in 25 daily fractions.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5125.
No positive effect of postmastectomy radiotherapy on mortality at 20 years in pre menopausal women with stage II breast cancer also treated with adjuvant oral cyclophopsphamide. South Sweden Breast Cancer Group, trial SBII:I.
Authors: Killander F , Anderson H , Möller T , Rydén S , Malmström P 
Published: December 2010

Abstract
Abstract #5128
Purpose: To study long term loco-regional recurrence rate and survival after postmastectomy radiotherapy in combination with oral cyclophosphamide in premenopausal women with stage II breast cancer.&#x2028; Study design: A three-armed randomised, multicenter, phase III trial comparing 1) Radiotherapy (RT) 2) RT+ oral cyclophosphamide for one year (RT+C) and 3) cyclophosphamide only (C).&#x2028; Radiotherapy was administered with 48 Gy in 20 fractions to chest wall and locoregional lymph nodes (Arwidi Å, Acta Oncol Scand 18:273-281, 1979). Cyclophosphamide was prescribed as 12 courses of 130 mg/m2 od for14 days every 4 weeks.&#x2028; Patients and methods: 367 patients from 15 departments in Southern Sweden, representing 80% of all eligible patients, were included in the trial between 1978-1983; n=124 (RT), n=118 (RT+C), n=125 (C). Median age was 47 years, median tumour size was 25 mm, and 33 % of the patients were lymph node negative. Median follow up for survival was 24 years and 21 years for other events.&#x2028; Results: RT reduced the risk at twenty years for locoregional recurrence in C treated patients with 75 %, 13.9 vs 3.5 %. The risk reduction was highly significant in both N0 and N+ patients. RT did not decrease systemic disease or mortality, see table 1. Chemotherapy did not decrease mortality when added to radiotherapy, though difficult to evaluate because of lack of information on delivered doses in many cases.&#x2028; &#x2028; Conclusion: Postmastectomy radiotherapy reduces loco regional recurrences in this premenopausal population, but no effect was seen on mortality at 20 years. Possible explanations are 1) low number of loco regional recurrences and superior survival in comparison to other trials investigating postmastectomy radiotherapy, which might have modified the effect of RT on survival, 2) too low intensity of adjuvant, single agent chemotherapy, and 3) chance, since relatively small study with little power.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5128.
Radiation induced molecular modulations in human breast adenocarcinoma cells after single (10Gy) and fractionated (2Gy x 5) dose irradiation.
Authors: Madhusoodhanan R , Terence HS , Aravindan N 
Published: December 2010

Abstract
Abstract #5133
Background: Radiotherapy a recognized treatment modality for breast cancer patients is now considered mandatory for most patients undergoing conservative surgery and is considered appropriate for women at high risk of recurrence after mastectomy. However, relapse due to radio-resistance of cancer cells significantly affects the success of radiotherapy and cancer patient survival. Ascertaining the fractionated irradiation (FIR) modulated molecular targets is important to make tumors more susceptible to molecular targeted therapy. Accordingly, we investigated the (i) expression of 84 genes representing 6 functional pathways including Cell cycle and DNA damage repair, Apoptosis and cell senescence, Signal transduction and transcription, Adhesion, Invasion and metastasis and Angiogenesis; (ii) nuclear translocation and DNA-binding activity of NFκB and; (iii) expression of radio-responsive TNFα, IL-1α, pAKT, cIAP1, cIAP2 and survivin molecules after single dose (SDR) radiation and FIR protocols in human breast adenocarcinoma cells.&#x2028; Methods: MCF-7 cells exposed to either SDR (10Gy) or FIR (2Gy x 5 days) and harvested after 24h were analyzed for alterations in gene expression using real-time Q-PCR-profiling. NFκB-DNA binding activity was analyzed using electrophoretic mobility shift assay and pIκB levels was measured using immunoblotting. Relative changes in the expression patterns of TNFα, IL-1α, pAKT, cIAP1, cIAP2 and survivin were determined using Q-PCR analysis and immunoblotting.&#x2028; Results: Compared to the SDR, FIR treated cells showed an induced expression 61 (Cell cycle & DNA damage repair - 12, Apoptosis & cell senescence - 10, Signal transduction & transcription - 7, Adhesion - 8, Invasion & metastasis – 11 and Angiogenesis – 13) genes. Furthermore, we observed a relatively induced DNA binding activity of NFκB and phosphorylation of IκBα after FIR. Like-wise, we observed an induced expression of TNFα, IL-1α, pAKT, cIAP1, cIAP2 and survivin mRNA in cells exposed to FIR. The changes in these genes were confirmed at the protein level.&#x2028; Discussion: These results along with the differential gene expression pattern support our hypothesis that FIR can induce molecular targets. In this initial analysis, NFκB and known NFκB regulated radio-responsive genes were found to be modulated. Currently, we are in the process of identifying similar FIR-induced targets and evaluate their potential for selective drug-targeted manipulation.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5133.
Prone accelerated partial breast irradiation using cone-beam CT (CBCT) guidance.
Authors: Lymberis SC , Becker SJ , Gidea-Addeo D , Jozsef G , DeWyngaert KJ , Formenti SC 
Published: December 2010

Abstract
Abstract #5136
Introduction: Prone external beam partial breast irradiation when used for a carefully selected subset of patients has been shown to have excellent long term control and cosmesis (Formenti et al. IJROBP 60(2): 493-504 2004). We used Cone-beam CT (CBCT) to visualize the tumor bed target prior to each daily fraction of partial breast irradiation. The purpose of this study is to measure the residual error in soft tissue positioning after alignment based on skin marks and MV portal imaging for patients treated on a prospective prone APBI study (3000cGy in 5 fractions over 5 days).&#x2028; Methods: Twenty-five post-menopausal women with pT1 breast cancer have consented on our NYU partial breast protocol using CBCT. Twenty-three patients have been simulated and treated in the prone position on a specially designed mattress. After initial skin mark setup and alignment, MV portal imaging with shift using the tangent beams eye view was used to optimize setup for the first 6 patients (Group I). For all daily fractions, CBCT was performed with the Varian On-Board Imager kV imaging system with a 35cm field of view and a 2.5mm slice thickness. CBCT was compared with the planning CT to shift the patient and evaluate the residual error in setup. The residual error from CBCT setup after optimal portal imaging was recorded for each patient. For the subsequent 17 patients (Group II), portal imaging was performed without shift to calculate the residual error from CBCT setup representing skin mark setup.&#x2028; Results: At the time of this report, 23 patients have been treated with all 5 fractions. The values for the residual error detected after cone-beam CT for Group I (after skin mark set up and portal imaging) and for Group II (after skin mark setup alone) are compared and shown in Table 1.&#x2028; Conclusions: In this preliminary study with a small number of patients, the residual error was minimal, around 2 mm. Therefore, for patients immobilized on our customized mattress, a reproducible and accurate prone APBI setup can be achieved with use of CBCT. However, given the very small residual error detected clinicians should be weary of indiscriminant use of CBCT for PBI. Concerns over contralateral breast dose and carcinogenic risk should limit the routine use of CBCT imaging for breast radiotherapy unless larger studies demonstrate improved accuracy of treatment delivery with CBCT.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5136.
Ovarian ablation by radiotherapy; is it still an option for the ovarian function suppression in endocrine responsive premenopausal breast cancer patients?.
Authors: Bese NS , Iribas A , Oksuz DC , Atkovar G , Ober A 
Published: December 2010

Abstract
Abstract #5137
Background; Although surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a resonable alternative. Data regarding the use of pelvic radiotherapy (RT) for ovarian ablation is very limited and in 10thSt Gallen consensus meeting, ovarian radiation was overwhelmingly rejected. In this retrospective study we evaluated the efficacy of RT for ovarian function suppression in 118 premenopausal breast cancer patients.&#x2028; Materials and Methods; 153 breast cancer patients had RA between the years 1979 and 2002 at the single center where this study was performed. 19 patients who received chemotherapy within 12 months of RA, and 16 patients who were lost to follow-up within 6 months following RA, were not included into the analyses. All patients were premenopausal and the median age at the initiation of RA was 39 years (range, 21- 52 years). 96 of 118 patients (82%) underwent RA for metastatic disease, 17 patients (14%) received RA as the systemic treatment after locoregional recurrences and 5 patients (4%) had RA as an adjuvant treatment. 97 patients (82%) received only RA as their systemic treatment, 20 patients (17%) had RA with tamoxifen and one patient (1%) had RA with aromatase inhibitors. RT was given with either Co-60 or 15 MV photons of the linear accelerator. A modified pelvic volume was irradiated with opposing anterior and posterior fields, and the dose was prescribed to midplane. The median total dose used for RA was 15Gy in 4 fractions (range 5Gy single fraction-36Gy in 18 fractions).&#x2028; Results; As the efficacy of RA, data regarding the menstrual status were collected. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. 88 patients (75%) experienced amenorrhea in 2 months after pelvic RT. 5 patients (4%) who had still normal menstrual functioning after 6 months of RA had estrodiol and follicle stimulating hormone measurements. As they were found to have premenopausal levels, 3 of them received surgical and 2 of them received medical ablation. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24,5 months (range; 6-167 months), no late severe complications that could be attributable to RT were reported. The total RT dose (more than 15Gy) were found to be significant on the rate of ovarian ablation with Mann Whithney U-test (p=0.02).&#x2028; Conclusion: Ovarian ablation was achieved with a rate of 96% without any major acute and late toxicity using pelvic RT. It should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5137.