bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-11-13: A Multi-Institutional Assessment of the Feasibility, Implementation, and Early Clinical Results with Noninvasive Image-Guided Breast Brachytherapy for Tumor Bed Boost
Authors: Hamid S , Ackerman S , Arthur D , Benda R , Cavanaugh S , Kuske R , Prestidge B , Quiet C , Sha S , Wazer DE. 
Published: April 2011

Abstract
Background: Noninvasive image-guided breast brachytherapy (NIIGBB) is an FDA-approved, commercially available (AccuBoost®, Billerica, MA) mammography-based, breast brachytherapy system whereby the treatment applicators are centered on the planning target volume (PTV) to direct 192Ir emissions along orthogonal axes. This study evaluates the feasibility, implementation, and early results of NIIGBB for breast tumor bed boost in combination with external beam whole breast radiation therapy (WBRT), as part of post-lumpectomy radiation.
Material and Methods: A privacy-encrypted online data registry was created to collect clinical and technical information from 8 independent academic and community-based institutions. Data were collected from consecutive 110 individual women with early stage breast cancer after breast conserving surgery, who received adjuvant WBRT (mean dose 48.3 ± 2.5 Gy) and tumor bed boost with NIIGBB between July, 2007 and March, 2010. Of the patients, 74% had invasive cancer, with 80% ER+ and 34% HER2+. NIIGBB was delivered before, during, or after WBRT in 57%, 39%, or 4% of the patients. Patient age and lumpectomy cavity size ranged from 32-88 yrs and 0.1-5.3 cm, respectively. Boost dose was delivered in 1.9 ± 0.3 Gy/fx for a total of 12.9 ± 3.4Gy. Toxicity and cosmesis were evaluated after radiation therapy and graded according to the Common Toxicity Criteria (v3.0) and the Harvard scale. Median follow up was 6 months (1-17 months).
Results: Grade 1-2 skin toxicity was observed in 18%, 7%, and 0% during the acute (1-3wks), intermediate (4-26 wks), and late-intermediate (&gt;26wks) periods. There were no Grade 3 or higher skin toxicity events. At 6 months, for the entire cohort, cosmetic grading was excellent, good, fair/poor in 52%, 48%, and 0%. The breast compression achieved for each treatment session was remarkably consistent with a mean mammographic plate separation of 6.4 ± 0.3 cm. Breast compression was scored as “uncomfortable” when NIIGBB was delivered before or during WBRT. The mean total duration of set-up and treatment per fraction was 16.7 ± 2.1 min. For each patient, the fraction-to-fraction variability in estimated PTV was low as 69% of treatments were completed with the same applicator size.
Discussion: These data indicate that NIIGBB is feasible and can be consistently implemented in a broad array of practice settings. Preliminary evaluation suggests that NIIGBB is associated with acceptably mild normal tissue toxicity and favorable early cosmetic results. The application of
NIIGBB before completion of WBRT may be associated with better patient tolerance at the expense of slightly less favorable short-term cosmetic outcome.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-13.
Abstract P4-11-14: Pulsed Reduced Dose-Rate Radiotherapy: A Re-Irradiation Strategy for Breast Cancer Patients with Brain and Spinal Cord Metastasis
Authors: Howard SP , Richards GM , Robins HI , Mahler PM , Wolfgang TA. 
Published: April 2011

Abstract
Background: Radiotherapy delivered at reduced dose-rates has the potential to preferentially reduce normal tissue toxicity, while still yielding almost identical tumor cell kill due to the superior repair capacity of late responding normal tissue. In conventional radiotherapy a 2 Gy dose is delivered at a dose-rate of 4-6Gy/min. A reduced dose-rate can be obtained by dividing a standard treatment fraction into a number of sub-fractions delivered in a pulsed manner separated by a fixed time interval. This increases the overall treatment time, allowing normal tissue repair during these sessions. Radiobiological modeling shows that a 2 Gy fraction can be delivered in a series of 0.2 Gy pulses separated by 3-minute intervals, creating an effective dose-rate of 0.0667 Gy/min. We have termed this re-irradiation technique pulsed reduced dose-rate radiotherapy (PRDR).* Methods: Between November 2000 and April 2010, 21 previously irradiated and heavily pretreated patients (pts) with progressive metastatic breast cancer were re-irradiated with PRDR to the whole brain (WB) (15) or spinal cord (SC) (6). The mean prior RT dose to the whole brain was 34.5 Gy (range 30-40 Gy) and the spinal cord was 39.9 Gy (range 30-50 Gy). A mean PRDR dose to the WB of 27.8 Gy (range 18-36 Gy) and SC of 31.3 Gy (range 28-40 Gy) was delivered in 1.8 or 2.0 Gy per fraction. Results: Mean overall survival (OS) of pts treated to the WB was 5.9 months (M) (range 0.5-21.3 M) and for pts treated to the SC was 18.9 M (range 5.6-43 M); 2 pts remain alive as of this report. Treatment was well tolerated: no grade 4 or 5 acute toxicities or grade 3 or 4 late toxicities were observed. Despite a mean cumulative dose of 64.9 Gy (range 54-80 Gy), there was no clinical or radiographic evidence of radionecrosis and/or neurological sequela. There appeared to be a correlation between KPS and OS. Conclusions: PRDR is a well-tolerated and effective radio-therapeutic method for the treatment of breast cancer patients with progressive metastatic CNS disease that have received prior radiotherapy.
* Reirradiation of Large-Volume Recurrent Glioma with Pulsed Reduced-
Dose-Rate Radiotherapy. Adkison JB, Tome W, Seo S, Richards GM,
Robins HI, Rassmussen K, Welsh JS, Mahler PA, Howard SP.
Int J Radiat Oncol Biol Phys. 2010 May 14. [Epub ahead of print] PMID:
20472350
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-14.
Abstract P4-11-22: The Role of Postmastectomy Radiation in Breast Cancer Patients with One to Three Positive Axillary Lymph Nodes
Authors: AboTouk NA , Zayed DH , Abdulla MM , Younies SG. 
Published: April 2011

Abstract
Background: Adjuvant radiotherapy in T1-T2 invasive breast carcinoma and 1-3 positive lymph nodes is controversial due to discrepancies in the reported locoregional recurrence risks and survival data. Purpose: This work aims to explore the effectiveness of postoperative radiation therapy in patients with 1-3 positive axillary lymph nodes treated by modified radical mastectomy with systemic chemotherapy with or without hormonal treatment on locoregional recurrence and survival rates. Patients and methods: One hundred and thirteen breast cancer patients with T1 or T2 tumors and 1-3 positive axillary lymph nodes, treated by modified radical mastectomy were registered in Clinical Oncology and Nuclear Medicine Department of Mansoura & Tanta University Hospitals in the period between January 1995 and December 1998. Of the 113 patients, 55 patients received postoperative radiotherapy while 58 patients did not receive it. Results: Postoperative radiotherapy reduced the incidence of locoregional recurrence from 18.2% to 5.2% (P=0.03). Distant metastases was 22.4% in the radiotherapy group of patients in comparison to 40% (P= 0.04). Disease free survival and overall survival were prolonged with postoperative radiotherapy received group (P= 0.03, 0.05) respectively. The risk factors including tumor size, grading and number of dissected axillary lymph nodes were of statistically significant value regarding both locoregional recurrence rates and survivals on the univariate analysis. On multivariate analysis they were statistically significant regarding disease free and overall survivals. Conclusion: Postoperative radiotherapy significantly reduces locoregional recurrence and survival in patients with 1 -3positive axillary lymph nodes. Patients with high risk factors including tumors ≥2cm, grade III and inadequate lymph node dissection are more likely to benefit from radiotherapy.
Key words: breast cancer, postmastectomy radiation, Positive lymph nodes, locoregional recurrence, risk factors.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-22.
Abstract P5-01-04: Preoperative PET-CT Staging of Axillary Node Positive Breast Cancer
Authors: Ni Mhuircheartaigh NM , Kell M , Flanagan FL , Hargaden GC , Fenlon HM , Gorey TF , Stokes M , Salman RR , Smith CS. 
Published: April 2011

Abstract
Purpose: 18F-FDG PET CT is a powerful diagnostic tool, which has enhanced systemic staging in oncology. Our aim was to evaluate the utility of performing staging PET-CT on patients with biopsy proven metastatic axillary lymph nodes that had clinically occult distant metastatic disease and to assess any change in management arising from it. Materials & Methods: All patients with newly diagnosed breast cancer undergo axillary ultrasound and cytology of suspicious lymph nodes, and those with positive cytology undergo pre operative PET-CT. Nodes were classified on ultrasound according to assessment categories R1-R5. PET-CT images were acquired with a Siemens Biograph High Resolution 16 slice PET/CT scanner using full dose CT and intravenous contrast. Results: Eighty two patients were identified with positive axillary cytology following ultrasound biopsy and underwent PET-CT; 28/82 patients (34%) had extra axillary disease. In total 30 patients (37%) had a change in management due to the PET-CT findings. 2 patients had more extensive surgery than previously planned, 7 patients (8%) had an extended radiation field and 21 patients (26%) were treated for distant metastases. Discussion: The detection of metastatic disease beyond the axilla has important implications for treatment options and survival. We detected clinically overt metastatic disease beyond the axilla and altered management in 37% patients due to the PET/CT findings. On this basis we recommend PET-CT for this preoperative cohort of patients with node positive breast cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-04.
Abstract P5-01-13: The Clinical Role and Cost Effectiveness of Breast-Specific Gamma Imaging (BSGI) in the Management of Patients with Negative or Indeterminate Mammographic and Sonographic Findings and an Unresolved Diagnostic Concern
Authors: Ward BH , Bohm-Velez M , Kieper D , Chang TS , Straka MR. 
Published: April 2011

Abstract
Background: BSGI is a molecular imaging technique increasingly used to aid in the management of patients with negative or indeterminate mammograms and an unresolved clinical concern such as indeterminate densities, new vague calcifications, bloody nipple discharge, focal breast pain or palpable masses; especially in those of elevated risk and patients with dense breast tissue.
Purpose: This study examines the role and cost effectiveness of BSGI in providing additional information when conventional imaging is indeterminate and greater confidence is required to improve diagnostic accuracy.
Methods: This is a retrospective analysis of patients in our practice for whom BSGI was recommended due to an unresolved clinical concern following negative (BI-RADS 1 or2), indeterminate (BI-RADS 0 or 3), or discordant findings on mammography (MMG) or ultrasound (US). For all modalities, the radiologist had the patient's history and imaging studies available to them at the time of interpretation. BSGI studies were classified as negative (BI-RADS 0-3) or positive (BI-RADS 4-5). Biopsy or follow up imaging was performed as recommended by the radiologist. Pathology or 6 month follow up imaging was used as the gold standard and were classified as negative (benign pathology or no evidence of malignancy on follow up imaging) or positive (biopsy proven cancer).
Results: There were 95 patients with 102 regions of concern, yielding 15 biopsy proven malignant lesions and 87 benign findings on pathology or follow up imaging. BSGI was positive in 12 malignant and 33 benign lesions and negative in 54 benign lesions, yielding a sensitivity of 80% and a specificity of 62%. The negative predictive value of BSGI in this population was 95%.
Conclusion: BSGI contributed significantly to patient management by detecting cancer in 12 of the 95 patients (12.6%). The Medicare reimbursement rate for BSGI in our area is $203.26. Therefore the cost per cancer diagnosis in this population was approximately $1,608.35. If these patients had been sent for breast MRI, $1,026.38 Medicare locally, the cost per diagnosis would rise to $8,129.07. BSGI is a useful, cost effective, complimentary tool in the diagnostic work up of patients when a diagnostic concern remains after negative or indeterminate conventional imaging.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-13.
Abstract P5-03-03: DNA Methylation of the Estrogen Receptor (alpha) Promoter Is Higher in Triple Negative Breast Cancers Compared to the ER Negative Sub-Type
Authors: Prabhu JS , Wahi K , Correa M , Manjunath S , Rao RN , Shastry SB , Tirumalai SS. 
Published: April 2011

Abstract
Background: The incidence of Estrogen Receptor alpha (ER) negative breast cancer and triple negative cases in India is twice that of Western Caucasians. The underlying causes for this two fold difference are unclear. DNA methylation of the ER promoter is one of the mechanisms of gene silencing. Recent data from the West indicate that the ER promoter is weakly methylated in a majority of patients independent of ER status. Data from an Indian cohort found 66% of ER negative breast tumors to be methylated at the ER gene. However, the technique used, Methylation specific PCR (MSP) suffers from a number of disadvantages such as false priming and low specificity. We have checked the methylation status of ER promoter A by a quantitative method and correlated it with clinicopathological parameters such as ER, progesterone receptor (PR) and Her2 protein status.
Materials and Methods: Tumor sections from 51 cases of primary invasive carcinomas were used for DNA extraction and bisulphite conversion. We adopted a quantitative method, Methylight assay for estimating the methylation status of the ER gene. Percentage Methylation Ratio (PMR) was computed and graded according to previously published standards. Methylation specific PCR was done for all these samples for comparison. Grade and Lymph node (LN) status were assessed. Immunohistochemistry was done to examine the status of ER, PR and Her2 protein.
Results: 16.6% of the ER negative tumors were moderately methylated (PMR score 5-50) at the ER promoter while none of the ER positive tumors were methylated to the same extent. Among the Triple Negative (TN) tumors in our cohort, 25% were moderately methylated. MSP tends to overestimate the methylated tumors and indicated that 43.5% of the ER negative tumors and19.2% of ER positive tumors were methylated. Discussion: A subgroup of ER negative and triple negative Indian patients have enhanced methylation of the ER gene. However this does not account for the doubling of ER negative incidence. Our demographics of a large pre-menopausal population might explain some part of this increase. Methylation of ER promoter was highest in TN tumors. This finding hints towards epigenetic dysregulation being a trait of TN tumors. The possibility of reversing the ER status from negative to positive in the clinic has raised an interest in the mechanism by which ER is lost.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-03-03.
Abstract P5-03-07: Adiponectin Deficiency Accelerated Breast Cancer Development and Promoted Cholesterol Accumulation in Mammary Tumors of MMTV-Polyomavirus Middle T Antigen Mice
Authors: Liu J , Xu A , Wang Y. 
Published: April 2011

Abstract
Breast cancer is the most common cancer in women. Visceral obesity and body weight gain are associated with the increased risk of postmenopausal breast cancer. Adiponectin is an adipokine possessing anti-tumor activities against various types of obesity-related cancers. The present study has established a MMTV-polyomavirus middle T antigen (PyVT) transgenic mouse deficient with adiponectin (ADN) expression. Compared to the control mice [PyVT(+/−)ADN(+/+)], the development of mammary tumors in mice lacking this adipokine [PyVT(+/−)ADN(-/-)] was significantly accelerated. While the serum total cholesterol was progressively decreased from week 11 onwards, the cholesterol content in tumor tissues was elevated in both types of mice. The ratio between serum LDL-cholesterol and HDL-cholesterol was significantly higher in PyVT(+/−)ADN(-/-) mice than that in PyVT(+/−)ADN(+/+) mice. Adiponectin was able to inhibit cholesterol uptake in both MDA-MB-231 human breast cancer cells and the primary tumor cells isolated from PyVT transgenic mice. These data demonstrated that the anti-breast cancer activity of adiponectin was at least in part attributed to its suppressive effects on cholesterol accumulation in mammary tumors.
This work is supported by Research Grants Council of Hong Kong (Project no.777908M). Adiponectin knockout mice were kindly provided by Dr. Lawrence Chan at Baylor College of Medicine, who generated these mice with the support of the US National Institutes of Health grant HL-51586.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-03-07.
Abstract P5-03-08: Overexpression of AIB1 mRNA in Breast Cancer Inversely Correlates with Estrogen Receptor Positivity
Authors: Lee A , Lee K , Chae BJ , Song BJ , Jung SS , Kang CS. 
Published: April 2011

Abstract
Background: The AIB1 is a steroid receptor coactivator that promotes the transcriptional activity of nuclear receptors such as estrogen receptor. It is overexpressed at the mRNA level in up to 60% of primary breast carcinomas.
Methods: In situ hybridization to examine AIB1 mRNA expression was performed in 113 breast carcinomas in the Catholic university of Korea, from Jan. 2004 to Dec. 2008. We investigated the prognostic significance of AIB1 and the correlation of immunohistochemical staining results of estrogen receptor(ER), progesterone receptor (PR), and Her2/neu. Results: AIB1 mRNA overexpression showed in 55 of 113 (48.7%) breast carcinomas. AIB1 mRNA expression was significantly associated with T stage (P=0.002), but not associated with age, lymph node metastasis, histologic type and histologic grade. High expression of AIB1 mRNA was inversely correlated with expression of ER (P=0.011, R=-0.241) and not significantly associated, but also adversely related, with expression of PR (P=0.101, R=-0.157). AIB1 mRNA overexpression was associated with positivity of Her2/neu (P=0.001, R= 0.311). Survival and recurrent free analysis did not reveal significant association with AIB1 expression. Conclusion: AIB1 mRNA overexpression could be involved in breast cancer by mechanism not totally dependent on steroid receptor cofactor, and may involved other estrogen independent growth pathway such as Her2/neu expression.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-03-08.
Abstract P5-04-02: Tumor Associated High Endothelial Venules (HEV) Predict Lymphocyte Infiltration and Breast Cancer Patients Clinical Outcome
Authors: Garrido I , Martinet L , Filleron T , Leguellec S , Rochaix P , Girard JP. 
Published: April 2011

Abstract
Even if lymphocyte presence within tumor tissues and its impact on cancer patient prognosis have been well documented past few years, the type of tumor vessels governing infiltration of effector cells into tumors remain to be determined. High endothelial venules (HEV) are specialized vessels for lymphocyte recruitment physiologically present in secondary lymphoidorgans also found in chronic inflammation that may impact lymphocyte recruitment and cancer patient's clinical outcome. We recently identified HEV like vessels in the peritumoral stroma of human solid tumors including melanomas, breast, colon, ovarian, and lung carcinomas. In order to better analyse the functional consequence of HEV presence within human solid tumors, we quantified HEV and tumor infiltrating lymphocytes by immunohistochemistry on serial tumor sections of 146 breast cancer patients. We demonstrate that HEV like vessels density within tumor stroma is an important predictor of CD3+, CD8+ T and B lymphocyte tumor infiltration suggesting an active role played by these vessels in peripheral blood lymphocyte migration into tumors. The breast tumor infiltrating lymphocyte phenotype associated with HEV presence was further characterized by large scale flow cytometry analysis in 30 freshly operated breast tumors. Breast tumors with a high density of HEV (HEVhi) have increased numbers of effector memory T cells (CD45RA-CD62L-) that display an activated mature phenotype (CD69+, Granzyme A+, Granzyme B+, perforin+). T cells with a naïve (CD45RA+CD62L+) and a central memory (CD45RA-CD62L+) phenotype are also specifically increased within HEVhi tumors as compared to HEVlo tumors. Finally, we analyzed the prognostic value of HEV in a retrospective cohort of 146 invasive breast cancer patients and demonstrate that HEV density within tumor stroma is an independent predictor of good clinical outcome. Indeed, HEVhi patients have a significantly longer metastasis free survival (MFS) (p&lt; 0,004), disease free survival (DFS) (P&lt;0,012) and overall survival (OS) (P&lt;0,023) than HEVlo patients. HEV like vessels, through the recruitment of high number of T lymphocytes and B lymphocytes from the periphery could limit the dissemination of primary breast tumors and prevent metastatic recurrence. Therefore, signals and cells that stimulate HEV differentiation within tumor stroma represent important solid tumors therapeutic target to modulate immune infiltration and patient's clinical outcome.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-04-02.
Abstract P5-05-03: FOXP3 Regulates Metastatic Spread of Breast Cancer Via Control of Expression of CXCR4 Chemokine Receptor
Authors: Overbeck-Zubrzycka D , Ali S , Kirby JA , Lennard TW. 
Published: April 2011

Abstract
Background: The transcription factor FOXP3 can regulate T cell migration by inhibiting expression of CXCR4, the receptor for the chemokine CXCL12. Increased expression of CXCR4 by breast cancer cells can drive metastatic migration towards sites which express CXCL12. Intracellular trafficking of FOXP3 to the nucleus is required in order for this protein to function. We hypothesised that FOXP3 gene is inactivated in breast cancer causing failure of nuclear localisation with subsequent increase in CXCR4 and potential for metastasis.
Methods: The expression patterns of FOXP3 and CXCR4 were measured at mRNA (PCR, real-time PCR) and protein (immunohistochemistry, immunofluorescence, flow cytometry) levels. A hundred sections of benign breast tissue, cancers, lymph node metastases and seven breast cell lines were examined with traditional and digital microscopy techniques. The results were correlated with pathological and clinical prognostic indicators of breast cancer.
Results: “Normal” breast epithelial cells (both patient-derived tissues and laboratory cultured cell lines) expressed FOXP3 in their nuclei and at the same time fail to express CXCR4. Breast cancer cells significantly overexpressed CXCR4 (P&lt;0.05), whereas FOXP3 expression was significantly decreased (P&lt;0.05) and confined to the cytoplasm with negligible nuclear expression [Figure 1]. Metastases expressed significantly less FOXP3 and more CXCR4 than primaries (P&lt;0.05). Transfection of cancer cells with wild-type FOXP3 cDNA expressing plasmid restored physiological nuclear FOXP3 expression. Discussion: We have found failure of FOXP3 nuclear localisation in breast cancer cells and an inverse correlation between this failure and CXCR4 expression [Figure 2]. Increased CXCR4 expression may adversely affect signalling pathways in favour of metastasis. Expression of wild type FOXP3 reverses this suggesting that breast cancer cells have mutations in the FOXP3 gene resulting in cytoplasmic localisation of the protein. Our findings suggest that disruption of FOXP3 nuclear localisation due to dysfunctional FOXP3 transcription factor may be a novel explanation for breast cancer invasion and metastases.
Figures available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-05-03.