bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2-08-07: Ex-Vivo High Resolution MRI of Sentinel Lymph Nodes Following Subcutaneous Injection of Superparamagnetic Iron Oxide Nanoparticles.
Authors: Douek M , ter Beek O , Johnson L , Pankhurst Q , Parikh J , Schaeffter T , Purushotham A , Charles-Eduards G 
Published: June 2012

Abstract
Background: Superparamagnetic iron oxide (SPIO) enhanced axillary MRI is a promising novel imaging modality that could be used to characterize sentinel nodes non-invasively. In order to better characterize lymph nodes and evaluate their morphological features, we imaged nodes ex-vivo using high resolution MRI, following a pre-operative subcutaneous injection of SPIO.
Material and methods: Prior to surgery patients received a circumareolar injection of SPIO (Endorem, Guerbet, Paris) into the upper outer quadrant of the affected breast. Sentinel lymph nodes excised during surgery were transported to the imaging department fresh. Nodes were placed in glass tubes and scanned using a Bruker 9.4T MRI system (T2 mapping: turbo spin echo, 16 equi-spaced TEs from 7.1 to 113.6 ms, TR = 1616 ms. T2* mapping: gradient echo, 6 equi-spaced TEs from 3.5 to 21 ms, TR = 1000 ms, flip angle = 30 degrees. Diffusion-weighted: spin echo, b-values 0 and 1000 s/mm2, TE = 18 ms, TR = 6500 ms.). Slice thickness was 1 mm with an in plane spatial resolution of 100μm. Image analysis was undertaken using Osirix (v3.8, 64-bit).
Results: A total of 40 nodes were successfully imaged, excised from 14 patients. The internal architecture of nodes was clearly seen and in the 3 involved nodes, a macrometastasis was identified. Three patients received a 4ml injection of SPIO and 11 patients, a 2ml injection. More SPIO deposition was seen within nodal sinuses following 4ml of SPIO, but there was no significant decrease in mean T2 value. Four nodes were re-imaged following formalin fixation and nodal architecture was unchanged with a trend towards an increase in mean T2 values within nodes. SPIO was identified in all sentinel nodes.
Discussion: Ex-vivo MRI with subcutaneous SPIO contrast, is a useful method for imaging and characterization of sentinel nodes. A better understanding of ex-vivo features is a useful aide to understanding the morphological features seen following in-vivo SPIO enhanced axillary MRI.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-07.
P2-09-04: Near Infra Red Quantum Dots as Novel Probes for Sentinel Lymph Node Biopsy.
Authors: Rizvi SB , Yang SY , Bala R , Shirin G , Seifalian AM , Keshtgar M 
Published: June 2012

Abstract
Background: Sentinel Lymph Node Biopsy (SLNB) is a standard procedure in breast cancer surgery. The current tracers for SLNB including the blue dye and radiocolloid, have various limitations like anaphylactic reaction to the dye and exposure of radioactivity to both patients and staff. Quantum dots (QDs) are fluorescent nanoparticles (2-10nm in diameter), with unique photophysical properties like enhanced photostability and size tunable emission wavelengths, that can potentially replace the current tracers for SLNB. QDs emitting in the Near Infra Red (NIR) range of the electromagnetic spectrum can be tracked in deep tissues as biological tissues are transparent to NIR wavelengths (700-2000nm). We have developed Near Infra Red emitting Quantum Dots (NIR QDs) as alternative probes for SLNB and set up a live NIR imaging system to track them in deep tissues.
Materials and Methods: NIR emitting QDs based on CdTeHg were synthesized by a one pot aqueous method and characterized using Transmission Electron Microscopy (TEM), UV-V is*** spectrometry and photoluminescence studies. 100μl of QDs (1mg/ml) were co-injected intradermally with blue dye into the hind legs of rat models (n=4) and compared to controls (n=4) which were injected with blue dye only. The procedure was conducted under inhalational anaesthesia using isofluorane and rats were monitored for hemodynamic instability for a period of 2 hrs after injection. QDs were tracked using a live NIR imaging system including an excitation light of 630nm, emission filter of 850nm and a Hamamatsu Orca 2 UV-Vis-NIR thermoelectrically cooled CCD camera.
Results: NIR QDs had a core diameter of 7nm on TEM and emitted at 860nm upon excitation with a 630nm light source. Within 3 minutes of an intradermal injection QDs entered the lymphatic tracts. The lymphatics converged to the groin and a small surgical incision at this site revealed the underlying sentinel lymph node with minimal dissection. The rats remained hemodynamically stable throughout the duration of the procedure with no significant difference in comparison with the controls.
Conclusion: NIR emitting QDs can be used for accurate localisation of the SLN prior to surgical incision, making this an even more minimally invasive procedure and possibly an office based procedure in the future. The nanosize, surface chemistry and deep tissue visibility of these novel nanoprobes allow relentless possibilities for in vitro and in vivo molecular and cellular imaging. NIR QDs can be conjugated to biomolecules for cancer localisation, detection of micrometastasis and image guided targeted drug delivery of chemotherapeutic agents. Further studies to investigate their in vivo biodistribution are in progress to take this technology one step closer to clinical application.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-04.
P2-10-06: Prospective Ultrasonographic Prediction of Sentinel Lymph Node Metastasis by Real-Time Virtual Sonography Constructed with Three-Dimensional Computed Tomography-Lymphography in Breast Cancer Patients.
Authors: Yamamoto S , Maeda N , Yoshimura K , Oka M 
Published: June 2012

Abstract
Background: Real-time virtual sonography (RVS) systems display virtual multiplanar reconstruction (MPR) images obtained from three-dimensional (3D) computed tomography (CT)-lymphography (LG), significantly improving preoperative detection of sentinel lymph nodes (SLNs). The purpose of this study was to prospectively evaluate SLN metastasis using an RVS system.
Methods: We identified SLNs in 73 clinically node-negative breast cancer patients using an RVS system to display in real time a virtual MPR obtained from CT volume data corresponding to the same cross-sectional image from ultrasonography (US). CT volume data were obtained using our original 3DCT-LG, which accurately detects SLNs in breast cancer. We then prospectively attempted to predict metastasis to SLNs. SLN metastases were assessed by measuring the cortex thickness in the presence of a visible hilum. We defined suspected SLN metastases as SLNs with a cortex thickness of at least 2.5 mm on the basis of our preliminary data. All patients underwent SLN biopsy and SLN metastases were examined pathologically with serial 2.0-mm-thick multiple slices.
Results: Suspected SLN metastases were identified in 24 of 73 patients, and 13 of these 24 patients were pathologically positive. The remaining 49 patients displayed no suspected SLNs, and 46 of these 49 were pathologically negative. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of measuring cortical thickness for predicting metastatic involvement of SLNs were 81, 81, 54, 94, and 81%, respectively.
Conclusion: If cortical thickness of the SLN is less than 2.5 mm, SLN metastasis is unlikely to be present. If cortical thickness of the SLN is at least 2.5 mm, preoperative fine-needle aspiration cytology may be recommended to verify the possibility of SLN metastasis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-06.
P2-10-07: Triple-Negative Breast Cancer May Have Ultrasonographic Features Mimicking Nonmalignant Lesions.
Authors: Wojcinski S , Farrokh A , Schmidt J , Hillemanns P , Degenhardt F 
Published: June 2012

Abstract
Background
Triple-negative breast cancer (TNBC) is known to have unique molecular, clinical and pathologic characteristics. Histological studies illustrate high mitotic counts, geographic necrosis, pushing borders of invasion, and stromal lymphocytic response. These growth patterns may also affect the appearance of TNBC in ultrasound.
Our study evaluates the ultrasonographic features of TNBC according to the ACR BI-RADS®-US classification system and compares these features with non-TNBC.
Materials and methods: Data of 385 consecutive breast cancer cases were collected from our hospital database. Digitally recorded ultrasound images were available for 292 patients. These images were interpreted according to the BI-RADS® system by an examiner blinded to the patients’ characteristics and histological results. The ultrasonographic features of TNBC (n=45) and non-TNBC (n=247) were compared using Fisher's exact test.
Results: TNBC was more common in younger patients and exhibited higher tumor grades and more advanced tumor stages. Focusing on the ultrasound features, TNBC was more likely to exhibit round or oval shape (35.5% versus 25.9% in non-TNBC) and the margin of TNBC was more frequently described as microlobulated (48.9% versus 37.7% in non-TNBC) instead of angular or spiculated. In TNBC the echogenic halo was significantly less often observed (46.7% versus 64.4% in non-TNBC, p=0.0302) and we found less architectural distortions (65.5% versus 84.3% in non-TNBC, p=0.0341). Regarding the posterior acoustic features, an enhancement was significantly more often observed in TNBC (26.7% versus 13.0% in non-TNBC, p=0.0391).
Discussion: TNBC and non-TNBC seem to have different ultrasonographic features. This can be explained by the unique pathologic profile of this breast cancer subtype. As some of the distinct ultrasound criteria of TNBC are associated with benign masses, TNBC may mimic nonmalignant lesions. Being familiar with these features can avoid false-negative classification of TNBC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-07.
P2-10-10: A Precision Comparison of Breast Ultrasound Images between Different Time Phases by Imaging Fusion Technique Using Magnetic Position Tracking System.
Authors: Nakano S , Fujii K , Yorozuya K , Yoshida M , Fukutomi T , Arai O , Mitake T 
Published: June 2012

Abstract
Purpose: We developed a real-time virtual sonography (RVS) in which realtime ultrasound (US) images and reconstructive virtual US images of the same cross-section are synchronized based on US volume data obtained on the same monitor using magnetic position tracking system (US-RVS). The purpose of this study was to evaluate the accuracy of US-RVS to compare breast US images between different time phases.
Materials and Methods: Between March 2010 and April 2011, US-RVS was performed in 108 consecutive patients with 112 target lesions for US (mean lesion size: 12 mm, 54 malignant and 58 benign). We used US-RVS system which consisted of sonography equipment, magnetic field generator, magnetic sensor, and workstation. To assess the accuracy of the US-RVS, we analyzed the sonographic re-identification rate of target lesions in different time phases.
Results: Among the 112 target lesions, 105 (94%) lesions were re-identified by US-RVS. The remaining occult 7 (6%) lesions were included one DCIS and 6 fibrocystic changes in terms of the histological type, and one mass lesion and 6 nonmass like lesions in terms of morphological feature. US-RVS enabled us to precisely compare arbitrary cross-sections of US images in any direction between different time phases independent of the operator's skill.
Conclusion: US-RVS, which requires no contrast medium and involves no radiation exposure, can be a useful modality for temporally tracking regions of interest using US.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-10.
P2-11-01: Validation of Predictive DNA Damage Response (DDR) Assay in Luminal B and Basal-Like Breast Cancers.
Authors: Rodriguez AA , Mao Y , Zhao H , Wong S , Chang JC 
Published: June 2012

Abstract
Background: We previously published a 69-gene DDR microarray signature that predicted for pathologic complete response (pCR) to anthracycline chemotherapy in women with basal-like breast cancer in two clinical studies1. Here, we sought to validate this predictive signature in independent data sets of breast cancers, selecting for basal-like and luminal B subtypes. We also customized a low density qRT-PCR array for use on formalin-fixed paraffin embedded tissue that will allow for prospective validation and clinical use.
Methods: Six independent validation sets were selected with known response to DNA damaging agents, containing either anthracyclines or cisplatin2-7. One independent data set with known response to the microtubulin agent docetaxel (non-DNA damaging) was used. 8 Using PAM50 genes, the tumors were first classified according to the molecular subtype. The predictive value of the 69-gene DDR assay was then correlated with known pathologic response, and the receiver operating curve determined.
We then performed qRT-PCR of these 69 genes with 5 controls, and correlated the expression of these genes with microarray RNA values in an additional 50 basal tumors. The data for individual genes was normalized, combined, and then hierarchically clustered.
Results: In the 170 basal tumors treated with DNA damaging agents, a high score predicted response in basal-like tumors. A, p&lt; 0.05. Conversely, for a non-DNA-damaging therapy, a high score significantly predicted for lack of response. B. In the 116 luminal B cancers, the DDR-assay also predicted for response to DNA damaging agent containing regimens with AUCs ranging from 0.67 to 0.80. C.

Microarray of the 69 DDR gene expression values was compared with Ct values by q-RTPCR low density array for 50 paired samples. High concordance between these two platforms (48/50 samples) was observed.
Conclusion: We have identified a robust predictive DDR assay that predicts for response to the DNA damaging agents, doxorubicin, epirubicin, and cisplatin in multiple studies, but not for docetaxel therapy. Future studies are underway to test for prediction of benefit of PARP1 inhibitor in basal-like and luminal B breast cancer.
References:
(1) Rodriguez AA et al: Breast Can Res Treat 123:189–96 (2) Tabchy A et al: Clin Cancer Res 16:5351–61 GSE 20271 (3) Farmer P et al: Nat Med 15:68–74, 2009 GSE 4779 (4) Popovici V et al: Breast Can Res 12:R5 GSE 20194 (5) Silver DP et al: J Clin Oncol 28:1145–53 GSE18864 (6) Desmedt C et al: J Clin Oncol 29:1578–86 GSE16446 (7) Iwamoto T et al: JNCI 264 GSE 23988 (8) Gluck S et al: Breast Can Res GSE 22358
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-01.
P2-11-07: Expression of Selected Predictive Markers in African American Women with Atypical Hyperplasia of the Breast.
Authors: Bandyopadhyay S , Cote M , Visscher DW , Ruterbusch J , Albashiti B , Alosh B , Frost MH , Hartmann LC , Fehmi RA 
Published: June 2012

Abstract
Invasive breast carcinoma in African American (AA) women differs significantly from their Caucasian (CA) counterparts in its incidence, morphology and outcome. These tumors are more likely to be high grade, hormone receptor negative, present at a younger age and at a higher stage. Evaluation and a better understanding of precursor lesions may help delineate the mechanisms underlying the development of breast cancer in these two groups. Atypical hyperplasia (AH) in the breast has been associated with an increased risk of developing cancer (relative risk∼4.0). Risk stratification of these women by identification of predictive biomarkers would be beneficial for optimal patient care. In our study we evaluated the expression of the following prognostic biomarkers: estrogen receptor (ER), Cyclooxygenase-2 (COX-2) enzyme and Ki-67 in AH in a cohort of AA women with benign breast biopsies.
AA women with benign breast biopsies from years 1997–2000 were retrieved from our departmental database. Clinical and follow up data was obtained from the SEER database. The hematoxylin and eosin (H & E) slides for these cases were reviewed by 2 pathologists, who were blinded to the outcome, and those with atypia were included in this study. Paraffin blocks were retrieved for immunohistochemical (IHC) analysis and standardized scoring methods applied.
A total of 1608 AA women had benign breast biopsies during the study period. We performed IHC analysis on 37 (2.3%) who were diagnosed with atypia (25 cases of atypical ductal hyperplasia (ADH) and 12 cases of atypical lobular hyperplasia (ALH)). Increased COX-2 expression was seen in 19 of 28 (67.8%) cases with AH. Of these, 13 of 19 cases (68.4%) were of ADH and 6 of 9 cases (66.7%) were of ALH. Twenty of 25 cases had a high expression of ER overall. Of these, 15 of17 (88.2%) of the positive cases was in the ADH category and 3 of 7 (42.8%) was in the ALH group.
Of 32 cases, only 3 cases showed a proliferation rate of &gt; 2% (9.4%) with Ki-67 IHC stain. All of these cases belonged to the ADH (21) category. In summary, the majority of AH cases showed increased COX-2 expression, although no differences were observed between lobular and ductal lesions. In contrast, ADH lesions appeared to exhibit increased reactivity for ER compared to ALH. Similarly, although rare, more ADH cases showed an increased proliferation rate compared to ALH. From our data, COX-2 and ER might be of prognostic significance in AA patients with AH. Larger studies with follow up are needed to understand this disease further.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-07.
P2-12-07: Pooled Analysis of Outcomes of T1a/bN0, HER2−Amplified Breast Cancer.
Authors: Amir E , Seruga B , Ocaña A , Carlsson L , Bedard P 
Published: June 2012

Abstract
Background: Breast tumors with HER2 amplification have a worse prognosis than those with normal HER2 expression. This finding is independent of tumor size and other classical prognostic factors used in the adjuvant setting. The prognosis of node negative, sub-centimeter (T1a/bN0) tumors is usually excellent. However, little is known about the prognostic impact of HER2−amplification in this group. This study therefore, aimed to evaluate the relative and absolute prognostic impact of HER2−amplification in T1a/bN0 tumors.
Materials and Methods: Published data from studies assessing the outcomes of patients with HER2−amplified, node negative, T1a/bN0 tumors were included in a pooled analysis. Odds ratios (OR), 95% confidence intervals (CI) and absolute risks were computed for recurrence and distant recurrence at 5 years. Pooled hazard ratios (HR) for disease-free survival (DFS), were also assessed.
Results: A total of 3 case-control studies were included in the analysis and comprised 485 patients with HER2−amplified breast cancer (57.3% were also hormone receptor positive) and 1096 patients with HER2−normal disease (82.2% were hormone receptor positive). Among the HER2−amplified group, 4.1% received trastuzumab and 18.6% received chemotherapy. In the HER2−normal group, 4.3% received chemotherapy Estimated median follow-up was 5.7 years. HER2−amplification was associated worse DFS (HR = 2.60, 95% CI 1.53−4.41, p&lt;.001) and increased odds for recurrence at 5 years (OR = 3.79, 95% CI 2.35−6.10, p&lt;.001). There was a non-significant trend towards increased odds of distant recurrence at 5 years (OR = 2.51, 95% CI 0.82−7.67, p=.11). Compared with HER2−normal cancers, those with HER2−amplification showed lower absolute probability of recurrence-free survival at 5 years (90.1% vs. 94.6%, p&lt;.001) and distant recurrence-free survival at 5 years (95.1% vs. 97.6%, p&lt;.001). Among HER2−amplified cancers, tumor size 0.6−1.0cm (T1b) was associated with a trend for higher odds of recurrence at 5 years compared with those 0.5cm or smaller (T1a, pooled OR = 1.58, 95% CI 0.96−2.60, p=.07).
Conclusions: HER2−amplification is associated with worse outcome in T1a/bN0 tumors. However, recurrence-free and distant recurrence-free survival at 5 years is excellent in this group, particularly in those with T1a tumors. These data question the role of adjuvant chemotherapy and trastuzumab in these patients unless associated with other high risk features. A differentially lower risk for distant recurrence suggests the possible role for more aggressive local therapy such as surgery and/or radiation therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-07.
P2-12-24: Resumption or Persistence of Menstruation after Cytotoxic Chemotherapy Is a Poor Prognostic Factor for Disease Free Survival in Premenopausal Patients with Early Breast Cancer.
Authors: Park IH , Han H-S , Lee KS , Kang HS , Lee S , Kim SW , Jung SY , Shin KH , Ro J 
Published: June 2012

Abstract
Background : We investigated the relationship between resumption or persistence of menstruation after chemotherapy and disease free survival (DFS) in premenopausal patients with early breast cancer.
Patients and methods : A total of 843 patients diagnosed with a stage I to III breast cancer between March 2001 and December 2006 were included in this study. All patients received cytotoxic chemotherapy after surgery; 411 (48.8%) with anthracycline based, 416 (49.3%) with anthracycline and taxane containing, and 16 (1.9%) with other regimens. We reviewed the medical records with a long term follow-up.
Results : The median age of patients was 41 years (range, 21–54 years) and the median follow-up duration was 6.2 years (range, 0.7−10.4 years).

Of all, 632 (75%) patients were hormone receptor (HR) positive who received tamoxifen therapy upon completion of chemotherapy. The chemotherapy induced amenorrhea (CIA) rate was 78.1% (n=658) and 52.4% (n= 442) experienced the resumption of period during the long term follow-up. One hundred two (12.1%) patients had persistent menstruation without CIA. The disease free survival (DFS) was significantly affected by the younger age (≤ 35 years) (HR=1.58, [95% CI, 1.10−2.70], P=0.014), advanced stage (stage 3) (HR=4.45, [95% CI, 3.17−6.25], P&lt;0.001), HR negativity (HR=2.21, [95% CI, 1.57−3.12], P&lt;0.001), HER2 positivity (HR=1.56, [95% CI, 1.04−2.34], P=0.032), and the resumption or persistent period (HR=2.03, [95% CI, 1.42−2.91], P&lt;0.001). HR negativity (HR=2.03, [95% CI, 1.43−2.90], P&lt;0.001), advanced stage (HR=4.40, [95% CI, 3.12−6.21], P&lt;0.001), and the resumed or persistent period (HR=1.85, [95% CI, 1.24−2.77], P=0.002) were remained significant factors for DFS on multivariate analysis.

Conclusions : A considerable proportion of premenopausal patients treated by chemotherapy experienced resuming period after CIA. The resumption or persistence of menstruation was a poor prognostic factor for disease free survival in premenopausal patients with early breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-24.