bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-02-04: Tissue oxyhemoglobin dynamics measured with functional optical imaging immediately after starting chemotherapy correlates with markers of cellular proliferation and inflammation in a rat breast tumor model.
Authors: Ueda S , Roblyer D , Cerussi A , Saeki T , Tromberg B 
Published: August 2014

Abstract
We have reported that a transient increase of oxyhemoglobin level measured 24 hours after the start of neoadjuvant chemotherapy using noninvasive Diffuse Optical Spectroscopic Imaging (DOSI) may be useful in discriminating nonresponding from reponding breast cancer patients (PNAS. 2011 Aug 30;108(35):14626–31). To elucidate the underlying biological mechanism, we compared optical measured hemoglobin levels to tissue biomarkers in a rat tumor model.
Method: An orthotopic mammary tumor model using Fischer 344 rats and MAT3B cells was used for this experiment. 16 mg of cyclophosphamide was administered (i.p.) in 15 rats after tumors had grown to a significant size. A wide-field functional imaging device that utilizes structured near-infrared light was used to measure superficial absolute concentrations of oxyhemoglobin (ctO2Hb) and deoxyhemoglobin (ctHHb) of the tumors. Rats were imaged and sacrificed (two per timepoint) at each of the following timepoints: baseline, 2, 6, 12, 24, 48, 96 hours, and day 8 following the injection. Resected tumors were sectioned after paraffin-embedding and representative slides were used for immunohistochemistry. Cellular markers of proliferation (measured by Ki67), apoptosis (Caspase3), NK cells (ANK61), and macrophages (MAC387) were counted in each slide using Image J software.
Result: Average tumors baseline values of ctO2Hb and ctHHb were 81.4 µM (±9.2 SD) and 22.4 µM (±4.1 SD) respectively. In most rats, both levels gradually increased from baseline to 24 hours after the injection and reached a maximum at 48 hours and then declined until Day 8. At 24 hours, ctO2Hb was significantly higher than baseline [96.8 µM (±8.8 SD) vs. 81.4µM (±9.2 SD), p = 0.003 using Student's t-test]. This trend was mimicked in the tissue markers of cellular proliferation and apoptosis, which peaked at 24 through 48 hours and then dropped. The average NK cell count was also found to rise consistently through the course of monitoring and reached the highest at day 8, while macrophage counts reached a peak at 48 hours and then declined. The differences between baseline and 24 hours for these were statistically significant: Ki67 [294 (±107 SD) vs. 115 (±68 SD), p = 0.0002], Caspase3 [2916 (±1383 SD) vs. 136 (±150 SD), p &lt; 0.0001], NK cells [635 (±329 SD) vs. 159 (±110 SD), p = 0.0001], and macrophage markers [281 (±260 SD) vs. 39 (±31 SD), p = 0.01].

Conclusion: We observed an increase in oxyhemoglobin early after chemotherapy, closely linked to changes in cellular proliferation, apoptosis, NK cells and macrophage accumulation. Early optical changes may be linked to chemotherapy-induced tumor metabolic and acute inflammatory responses.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-04.
Abstract P4-02-08: Quantitative Characterization of 3D Vasculature Spatial Patterns Within Tumor Microenvironment of Breast Cancer Stem Cells
Authors: Zhan M , Li F , Zhu Y , Ma J , Landua J , Wei W , Vadakkan T , Zhang M , Dickinson M , Lewis M , Rosen J , Wong S 
Published: August 2014

Abstract
The sustainment characters of cancer stem cells (CSCs) such as self-renew and differentiation to other tumor cells greatly depend on the tumor microenvironment, which is composed of many components, e.g. vasculature, extracellular matrix, epithelial cells, stromal cells, as well as nutrients and oxygen. As vasculature is an important factor for the CSC and tumor development, the understanding of their spatial patterns is essential for calibrating the CSC-microenvironment interactions in mathematical modeling. In this study, we acquired the vasculature in side tumors and normal breast tissues by using two-photon fluorescence microscopy, which enables 3D in vivo imaging. We developed an advanced vasculature segmentation approach for an objective and accurate quantification of the vasculature in 3D image volumes. The approach integrates supervoxel analysis and the orientation guided hidden Markov random field (ori-HMRF) modeling together to compensate for low quality images, e.g., low signal-to-noise ratio (SNR) and uneven background. By constructing a new feature space that combines the CIELAB color space and the coordinates space, the supervoxel analysis divides an image volume into subregions with local similar intensity and restricted regular shape, boundaries of which can delineate the vasculature boundaries accurately even in low intensity contrast regions. We further designed a set of features for the separation of blood vessel regions from the background. To make use of the context information, i.e. the continuity of vasculature, the ori-HMRF model is used to incorporate the consistency of vasculatures' orientation in order to reduce the false positives and negatives. Experimental results on image volumes from both breast cancer and normal breast tissues show that the proposed method can effectively reconstruct the vasculature structure with the CSC embedded tumor microenvironment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-08.
Abstract P4-02-09: Molecular Breast Imaging: the sensitivity of breast-specific gamma imaging (BSGI) as a diagnostic adjunct to mammography and ultrasound in a triple assessment protocol
Authors: Weigert JM , Kieper DA , Stern LH , Böhm-Vélez M 
Published: August 2014

Abstract
Purpose: BSGI is a diagnostic breast imaging procedure becoming more common in clinical breast practice. The goal of this work is to quantify its performance as an addition to mammography and ultrasound in detection of breast carcinoma when used in the community breast center setting.
Methods: A multi-center patient registry was maintained for all patients routinely sent to BSGI as part of their diagnostic work up. From the registry data, patients who had a mammogram followed by ultrasound and BSGI were selected for evaluation. The BIRADS rating schematic was used for mammography and sonography and a similar category system was used for the BSGI images. For each modality, the reports were classified as positive (categories 4–6) or Negative (categories 0–3). Needle and/or surgical biopsy were conducted as deemed clinically necessary and all patients who had a malignant diagnosis by pathology were entered into this analysis.
Results: 731 patients had all three imaging modalities as part of their diagnostic work up resulting in 180 malignancies confirmed by pathology: 29 ductal carcinoma in-situ, 110 infiltrating ductal carcinoma, 11 infiltrating lobular carcinoma, 9 papillary carcinoma and 21 mixed component malignancies. Mammography was positive in 130 (sensitivity = 72%) while ultrasound was positive in 114 (sensitivity = 63%) and BSGI was positive in 147 (sensitivity = 82%). The combination of mammography and ultrasound was positive in 163 cases (sensitivity = 90%) while the addition of BSGI provided positive findings for 177 malignancies resulting in a sensitivity of 98%.

A subsequent breast MRI detected one of the lesions missed by the three modalities while two lesions were found by pathology alone.
Conclusions: Of the three imaging modalities, BSGI provided the highest independent sensitivity and when added to the diagnostic workup, BSGI detected an additional 14 malignancies, increasing the sensitivity from 90% to 98%. Although it is beyond the scope of this work, it is interesting to note that the cost of the BSGI procedure is relatively low, about $320, and that in this population the BSGI specificity was 74%. In summary, when added to the diagnostic work up of patients in the community breast cancer, BSGI can improve the detection of breast malignancy when compared to mammography and ultrasound alone.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-09.
Abstract P4-03-03: Feasibility study of a new volume navigation system-guided breast biopsy method for incidental enhancing lesions detected by breast contrast-enhanced magnetic resonance imaging
Authors: Takahashi M , Jinno H , Hayashida T , Nemoto M , Tanimoto A , Kitagawa Y 
Published: August 2014

Abstract
Background: Incidental enhancing lesions (IELs) undetected by conventional imaging such as mammography and ultrasonography (US) have been reported in 16–29% of patients undergoing subsequent breast contrast-enhanced magnetic resonance imaging (CE-MRI). We recently assessed IELs by performing breast biopsies using a volume navigation system (V-Navi) which synchronizse real-time US images with reconstructed CE-MRI data side-by-side on the same monitor. The aim of this retrospective study was to evaluate the feasibility of V-Navi-guided biopsy method as an IEL diagnostic procedure.
Methods: We performed breast biopsies on 333 patients after mammography, US and CE-MRI (GE Signa Excite HDx 1.5T, USA) examinations between January 2011 and May 2012 at Keio University Hospital. Patients with IELs detected by CE-MRI underwent a second-look US and a bilateral CE-MRI in the supine position in order to achieve the same position as in the US. CE-MRI data was then fused with real-time US images using a V-Navi (Logiq E9, GE Healthcare, USA). When an IEL was identified, we performed a V-Navi-guided vacuum-assisted needle biopsy (11G) or an excisional biopsy after V-Navi-guided marking.
Results: US-guided and stereo-guided breast biopsies were performed on 77.2% (257) and 16.8% (56) of the 333 patients, respectively. Twenty patients (6.0%) had IELs detected by CE-MRI and all such IELs were identified by the V-Navi. Sixteen (80%) of those 20 patients had IELs clearly detected by the V-Navi and underwent V-Navi-guided needle biopsies. The four remaining patients (20%) had IELs that were not clearly detected by the V-Navi and they underwent excisional biopsies. The median IEL size was 8.8mm (range, 5.0–48) and the median procedure time for V-Navi-guided needle biopsies was 42 minutes. No major complications were encountered in any of the cases. Histopathologically, nine IELs (45%) had malignant findings of invasive ductal carcinoma (5/20) and ductal carcinoma in situ (4/20) and 11 IELs (55%) had benign findings of fibrocystic disease (10/20) and intraductal papilloma (1/20).
Conclusion: The V-Navi-guided breast biopsy method was shown to be a safe and effective diagnostic method for the assessment of IELs detected by breast CE-MRI.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-03.
Abstract P4-03-04: The potential use of Optical Coherence Tomography for intraoperative breast tumour margin width estimation
Authors: Wilson BC , Akens MK , Niu CJ 
Published: August 2014

Abstract
Total mastectomy and lumpectomy with radiation have been shown to have equivalent patient outcomes, which has likely contributed to the more widespread adoption of breast conserving surgery (BCS) procedures. Assessment of breast lumpectomy margin widths in both an accurate and timely manner is essential to successful breast conservation procedures. Current BCS methodologies have been reported to result in reoperation rates of up to 20–60%, which represents a significant and unmet need for improved margin assessment. High reoperation rates present both increased treatment risk to patients and increased burden on healthcare systems. In the USA alone, over 150,000 lumpectomies are performed per year at an average cost between $11,000 and $19,000 USD per procedure. Assuming a relatively modest average repeat operation rate of 25%, potentially preventable repeat surgeries represent an approximate cost to the US healthcare system of $500M (USD) annually.
Reducing the prevalence of repeat surgeries may be accomplished by providing faster and more accurate intraoperative tools for assessing margin widths during the time of the first surgery. One such potential technique involves the use of Optical Coherence Tomography (OCT) imaging, which uses light to produce images in much the same way that ultrasound produces images with sound. Compared to ultrasound, OCT provides decreased depth of penetration, but increased resolution capabilities. The increased resolution that OCT provides allows for the visualization of the internal cellular structure within a tissue sample and therefore, provides the potential ability to differentiate cancerous from normal or benign cells. We propose the use of an intraoperative OCT imaging system to provide near real-time imaging information about the internal structure of tissue samples excised during BCS procedures. Our hypothesis is that the overall rate of repeat operations can be reduced by providing a tool to assist surgeons with the task of margin width estimation during the time of surgery.
We have developed an early stage prototype OCT imaging system that has completed laboratory phantom and preclinical studies. This paper will present the capabilities of an OCT imaging system to provide margin assessment information in biological breast tissue mimicking phantoms. The phantoms were designed to encompass imaging characteristics across a wide range of human breast densities. The paper will go on to describe preclinical imaging that was done in tumor specimens excised from human breast cancer rat models. The results obtained in the phantom and preclinical studies suggest the potential for OCT as a near-real time, intraoperative imaging tool to aid surgeons with breast lumpectomy margin width estimation. To help realize this potential, further research is required in to the use of OCT during BCS.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-04.
Abstract P4-03-05: The Clinical Trial of New Optical Mammography
Authors: Ogura H , Yoshimoto K , Nasu H , Hosokawa Y , Matsunuma R , Ide Y , Yamaki E , Yamashita D , Suzuki T , Oda M , Ueda Y , Yamashita Y , Sakahara H 
Published: August 2014

Abstract
Objectives: Optical mammography (O-MMG), which utilizes near-infrared light for the detection of abnormal breast tissue, can be a potentially useful and non-invasive tool for the screening of breast cancer patients. Here we report on the preliminary results of our clinical trial using a time-resolved O-MMG system developed by Hamamatsu Photonics (Hamamatsu, Japan). In our past examination, negative results included cases with mismatch for breast cup because of small breast, lesion outside of cup because of big breast, and bad positioning. So, size and shape of a gantry was improved (3 cup sizes; S, M and L cup). We reported the initial experience of the improved O-MMG systems.
Materials and Methods: In principle, the technique involves sequential irradiation of the breast tissue with a pulsed laser with a wavelength of 760, 800 and, 830nm, which is then detected by the variable capacity gantry at multiple sites after passing through the breast tissue. Measurement time has improved to about 7 minutes (a third of the conventional measurement time). The data are analyzed and tomographic images of the absorption coefficient of the breast are then reconstructed based on our tomographic reconstruction algorithm. Between October 2011 and May 2012, fifteen patients with breast cancer and one patient with fibroadenoma participated in the trial.
Results: In patients with breast cancer, S cup was used for one patient, M cup for 12 patients and L cup for two patients. Five patients after neo-adjuvant chemotherapy were excluded from the analysis. The lesions were depicted as an area of high hemoglobin concentration in 7 of 10 patients with cancer. One lesion of fibroadenoma was also identified as an area of high hemoglobin concentration.
Conclusion: Further examination with our new O-MMG systems will be of interest.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-05.
Abstract P4-03-07: Angiogenic effect of bevacizumab and paclitaxel in metastatic breast cancer: evaluation by contrast-enhanced ultrasonography using Sonazoid®
Authors: Ito T , Mizuno H , Iiboshi Y , Yamamura N , Fujii H , Hitora T , Fujii R , Ohashi T , Nakagawa T , Izukura M 
Published: August 2014

Abstract
Agents targeting vascular endothelial growth factor (VEGF) have been validated as breast cancer therapeutics, yet efficacy can differ between tumor types and individual patients. Rapid noninvasive determination of response could provide significant benefits. We tested if response to the VEGF antibody bevacizumab and chemo drug paclitaxel could be detected using contrast-enhanced ultrasound imaging (CEUS).
The objective of this study was to evaluate contrast-enhanced ultrasound (CEUS) with contrast agent Sonazoid® injection as a predictor of tumor response.
Patients and methods: Ten patients with advanced and metastatic breast carcinomas treated were evaluated. Examinations were performed at baseline, after 2 and 4 weeks and every one month on antiangiogenic drug bevacizumab and chemo drug paclitaxel in tumor targets that were accessible to CEUS. Histological findings were obtained in all cases by ultrasound-guided 14 gauge core needle biopsy or 10 gauge vacuum-assisted biopsy. Each examination included a bolus injection of Sonazoid® and 40–60 seconds of raw linear data with an Aplio (Toshiba), Logiq (GE) and Ascendus (Hitachi-ALOKA) with a 8–12 MHz linear transducer. A low reduced mechanical index (MI) of less than 0.24 was chosen to avoid early gas bubble destruction.
The ethic committee of our institution approved this study. An informed consent was signed by each patient for the ultrasound examination and before administering for the contrast medium.
Results: A total of 60 examinations were performed. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed.
Conclusion: CEUS has advantages for real-time visualization and is a new noninvasive imaging technique which might be an effective tool for evaluating antiangiogenic drugs and chemo drugs in breast cancer.
The use of a noninvasive ultrasound approach may allow for earlier and more effective determination of efficacy of antiangiogenic therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-07.
Abstract P4-03-08: A new real-time image fusion technique, a coordinated sonography and MRI using magnetic position tracking system, improves the sonographic identification of enhancing lesions in breast MRI
Authors: Nakano S , Fujii K , Yoshida M , Kousaka J , Mouri Y , Fukutomi T , Ishiguchi T 
Published: August 2014

Abstract
Breast magnetic resonance imaging (MRI) is a method that can detect clinically and mammographically occult cancer foci. For lesions suspected to be malignant on the basis of breast MRI, targeted sonography can help determine whether the lesion is amenable to tissue biopsy using sonographic guidance. However, the reproducibility of sonography as well as interexaminer reliability in targeted sonography is still a clinical issue. Recently, we have developed real-time virtual sonography (RVS) that can coordinate a sonographic image and a MRI multiplanar reconstruction (MRI-MPR) of the same section in real time. Although RVS has been reported to be useful for breast cancers, only a few studies have investigated the size and positioning error between a real-time sonographic image and a MRI-MPR image. The purpose of this study was to evaluate the accuracy of RVS to sonographically identify enhancing lesions by breast MRI. Between December 2008 and May 2009, RVS was performed in 51 consecutive patients with 63 enhancing lesions. MRI was performed with the patients in the supine position using a 1.5-T imager with a body surface coil to achieve the same position as with sonography. To assess the accuracy of the RVS, the following three issues were analyzed: (i) The sonographic detection rate of enhancing lesions, (ii) the comparison of the tumor size measured by sonography and the MRI-MPR and (iii) the positioning errors as the distance from the actual sonographic position to the expected MRI position in 3-D. Among the 63 enhancing lesions, 42 (67%) lesions were identified by conventional B-mode, whereas the remaining 21 (33%) initial conventional B-mode occult lesions were identified by RVS alone. The sonographic size of the lesions detected by RVS alone was significantly smaller than that of lesions detected by conventional B-mode (p &lt; 0.001). The mean tumor size provided by RVS was 12.3 mm for real-time sonography and 14.1 mm for MRI-MPR (r = 0.848, p &lt; 0.001). The mean positioning errors for the transverse and sagittal planes and the depth from the skin were 7.7, 6.9 and 2.8 mm, respectively. The overall mean 3D positioning error was 12.0 mm. Our results suggest that RVS has good targeting accuracy to directly compare a sonographic image with MRI results without operator dependence.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-08.
Abstract P4-04-01: Combination of intratumoral CpG with systemic anti-OX40 and anti-CTLA4 mAbs eradicates established triple negative breast tumors in mice
Authors: Li J , Tandon V , Levy R , Esserman L , Campbell M 
Published: August 2014

Abstract
Background: Evidence is mounting across diverse datasets and scientific techniques implicating immune dysregulation in poor outcomes of high grade and/or triple negative breast cancers. A multimodal strategy to stimulate the immune system could be an effective therapeutic approach for breast cancer. CpG oligodeoxynucleotides are single-stranded DNA that stimulate dendritic cells and B cells by binding to Toll-like receptor 9 (TLR9). OX40 (CD134) is predominantly expressed on activated T cells and the binding of OX40 with an agonistic antibody (anti-OX40) leads to the proliferation and survival of T cells. Agonistic anti-OX40 antibodies can also reverse the suppressive effects of Treg cells. A third avenue is to target Cytotoxic T lymphocyte associated antigen (CTLA4), which plays a negative regulatory role in T cell activation and is also constitutively expressed on Treg cells. Blocking CTLA4 with an antagonistic antibody (anti-CTLA4) has been shown to enhance anti-tumor responses. In this study, we tested the combination of intratumoral (IT) CpG with systemic anti-OX40 plus anti-CTLA4 in a mouse model of triple negative breast cancer.
Methods: 4T1, an aggressive, triple-negative mammary carcinoma, was implanted orthotopically into syngeneic BALB/C mice. Treatment was initiated when tumors were ∼0.5 cm in the largest dimension. Mice were divided into 8 groups. Various combinations of PBS control, CpG, taxol, and anti-OX40+anti-CTLA4 mAbs were tested (Tables 1 and 2). CpG, 100 µg, was injected IT for 5 consecutive days (days 1–5); Taxol, 16 mg/kg, was administered IP on day 1; anti-OX40 (400 µg) and anti-CTLA4 (100 µg) were given IP on days 1 and 5. Mice were sacrificed once tumors became ulcerated or reached a diameter &gt;2 cm.
Results: As shown in Table 1, CpG alone, taxol alone, or the anti-OX40 + anti-CTLA4 combination each delayed the growth of established 4T1 tumors when compared to the untreated control group. However, the majority of the mice (except one in CpG treated group) died from tumor progression. The combination of CpG + anti-OX40 + anti-CTLA4 had the best anti-tumor effects, with 4 out of 5 mice having demonstrated complete regression of their tumors (Table 2). The addition of taxol to the combination of CpG + anti-OX40 + anti-CTLA4 did not improve the anti-tumor effect, and while there was a substantial delay in growth, only one animal achieved a complete regression.

Conclusion: Our study demonstrated that the combination of IT CpG with systemic anti-OX40 + anti-CTLA4 mAbs can cure mice with established triple negative breast tumors, supporting the possibilities of applying immune modulation approach in human triple negative tumors. Studies are on-going to further dissect the immunological mechanisms involved.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-04-01.