bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-12-05: Clinical features and outcomes of leptomeningeal metastasis in patients with breast cancer: a single center experience
Authors: Jo J-C , Kang MJ , Ahn J-H , Jung KH , Kim JE , Gong G , Kim HH , Ahn SD , Kim SS , Son BH , Ahn SH , Kim S-B 
Published: August 2014

Abstract
Background: Leptomeningeal metastasis (LM) is one of the major problems in managing metastatic breast cancer because of LM typically carries a devastating prognosis and often represents a terminal event. We analyzed the clinical features and outcomes of LM in patients with breast cancer.
Methods: We retrospectively reviewed the medical records of patients who were diagnosed with LM from breast cancer between 2002 and 2012 at Asan Medical Center.
Results: Of the 95 LM patients by cytologically proven (n = 81) or radiologically diagnosed (n = 14), 57 (60%) had an ECOG performance status (PS) ≥ 3, and the median age was 47 years (range, 26–72 years). The patients were diagnosed with LM after a median of 10.3 months (95% CI, 5.5–15.0 months) from the time of diagnosis of metastatic breast cancer. LM was present in 2 patients at the time of initial diagnosis. Twenty-three patients (24.2%) had isolated CNS metastasis, and 6 (6.3%) had only LM without any detectable metastasis sites. At the time of diagnosis of LM, 46 patients (48.4%) presented with coincidental failure of systemic disease control. Seventy-eight patients (82.1%) underwent intrathecal chemotherapy (methotrexate; n=78, thiotepa; n=11), resulting in one-third of cytologic negative conversion (n = 26), and 41 (43.2%) received systemic chemotherapy. The overall median survival time was 3.3 months (95% CI, 2.5–4.2 months) and 7.8% of the patients survived for more than 1 year. Overall survival tended to be better in patients who achieved cytologic negative conversion to intrathecal chemotherapy than those did not (median 4.5 months versus 3.2 months, P = 0.241). Overall survival was not different according to subtypes; hormone receptor (+), HER2 (+), and triple negative (median 3.6 months, 3.3 months, and 3.2 months, P = 0.937). Multivariate analysis demonstrated that ECOG PS ≥ 3 (HR = 2.09, 95% CI 1.21–3.58, P = 0.007), coincidental failure of systemic disease control at LM (HR = 3.01, 95% CI 1.76–5.15, P &lt; 0.001), and systemic chemotherapy after LM (HR = 0.40, 95% CI 0.24–0.68, P = 0.001) were independent factors associated with survival.
Conclusions: The prognosis for patients with LM from breast cancer was still poor. Systemic chemotherapy in addition to intrathecal chemotherapy might confer a survival benefit, even after the detection of LM.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-05.
Abstract P3-12-06: Clinicopathological Analysis of Breast Cancer Patients with Brain Metastases
Authors: Ushio A , Sawaki M , Fujita T , Hattori M , Kondo N , Horio A , Gondou N , Iwata H 
Published: August 2014

Abstract
Background: Recent advances in chemotherapy have enabled to control the progression of metastases from breast cancer except for the brain, highlighting the symptoms associated with brain metastases. In addition, improvement in our understanding of breast cancer biology changed the treatment strategy, possibly leading to improved outcomes in patients with breast cancer and brain metastases.
Object: The aim of this study was to investigate the correlation between biology of primary tumors and prognosis of patients with breast cancer metastasis to the brain.
Patients and method: Among 3,171 patients with primary breast cancer undergoing surgery at out hospital from 2003 to 2010, 35 patients (1.1%) who developed brain metastases, excluding stage IV at the initial diagnosis. We reviewed 35 patients for a correlation between survival and clinicopathological variables, including stage, hormonal sensitivity, HER2 expression status, the number of brain metastases, and treatment for brain metastases.
Results: The mean age of 35 patients was 52.1 years (range 22–68) and the median follow-up period was 41.0 months. The subtypes of primary tumors included triple-negative (TN) in 14 patients (40%), luminal in 11 patients (31.4%), luminal HER2-positive (luminal HER2) in 2 patients (5.7%), and HER2-positive (HER2) in 2 patients (5.7%). The duration from surgery to recurrence (disease-free survival, DFS, months) was 14.7 in TN, 26.5 in luminal, 29.8 in luminal HER2, and 31.0 in HER2. The duration from the first recurrence to the detection of brain metastases (months) was 7.2 in TN, 14.4 in luminal, 15.8 in luminal HER2, and 4.0 in HER2. The mean survival time after the diagnosis of brain metastases was 8.6 months (range, 0–40) with a survival time of ³ 1 year in 8/35 patients (23%) and that of &lt; 1 year in 21/35 patients (60%). Both DFS and the duration from the first recurrence to the diagnosis of brain metastases were shorter in TN compared with other subtypes. In HER2 subtype, DFS was long but, once recurrence was detected, the duration to the development of brain metastases was short. In multivariate analysis of clinicopathological variables (age, DFS, ER, HG, HER2, the number of brain metastases (solitary versus multiple), the site of initial metastasis (brain versus other organs), and the presence or absence of chemotherapy after brain metastases, revealed solitary brain metastasis (p = 0.002) and the initial metastatic site of brain (p = 0.003) to be independent factors predicting survival.

Conclusion: The clinical outcomes of brain metastases were different among tumor subtypes. Factors predicting survival in patients with breast cancer and brain metastases may be the site of initial metastasis, the number of brain metastasis, and local treatment for brain metastases.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-06.
Abstract P4-01-09: Screening breast magnetic resonance imaging (MRI) in early-stage breast cancer survivors
Authors: Dowton AA , Meyer ME , Ruddy KJ , Yeh ED , Partridge AH 
Published: August 2014

Abstract
Background: Limited evidence is available regarding the value of screening breast MRI in female early stage breast cancer survivors. We sought to evaluate outcomes of index screening breast MRI in breast cancer survivors in the modern era of breast cancer treatment and imaging.
Methods: Using a large prospective institutional database, we identified all women who underwent breast MRI between 7/2006 and 6/2008, were ≥ 1 year and ≤ 3 years after diagnosis of stage I-IIIa breast cancer, had remaining breast tissue after treatment, and had consented to a record review protocol at our center (95% uptake rate). Sociodemographic, disease, staging and treatment information (see table 1), indications and outcomes for breast MRI, as well as disease status at 2 years after the index MRI were ascertained.
Results: 643 patients were identified as having undergone at least 1 MRI of the breast(s); 248 (38.5%) were diagnostic MRIs (had identified clinical indication or imaging abnormality); 12 (2%) were missing clinical data; 383 (59.5%) were screening MRIs. 338/383 (88%) patients who had screening MRI had stage I-IIIa invasive breast cancer. 220/338 (65%) MRIs performed were index MRIs (index MRI defined as first MRI &gt;1 year post diagnosis). For this preliminary analysis, we include only the 155 patients (70%) who were within 1–3 years of diagnosis at the time of index MRI (see table 1 for patient and disease characteristics).
24/155 (15.5%) screening MRIs were considered not normal. Five women (21%) underwent biopsy based on abnormal MRI finding; 1 resulted in the detection of a local recurrence (4.2%, 95% CI=0.1%–21.1%). 3/131 patients who had a normal index MRI were found to have local/regional recurrence or contralateral breast cancer diagnosed within 2 years of the MRI (2.3%, 95% CI=0.5%–6.6%). A statistically significant difference in the proportions was not observed based on Fisher's test (p = 0.50). 6/155 patients (3.9 %) had a systemic recurrence in the 2 years following index MRI.

Conclusion: The vast majority of first screening breast MRIs obtained 1–3 years following treatment in early stage breast cancer survivors are normal, and very few detect cancer. Planned further analysis in this dataset will evaluate frequency of cancer detection in longer-term survivors. Additional research is necessary to determine the risks and benefits of screening breast MRIs being performed in this population.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-09.
Abstract P4-01-13: Practice patterns of MRI utilization for breast cancer treatment within the University of California system as part of the Athena initiative
Authors: Tokin CA , Ojeda H , Mayadev JS , Hylton NM , Fowble BL , Rugo HS , Hwang S , Hurvitz S , Wells C , Blair SL 
Published: August 2014

Abstract
Background: The appropriate utilization of Breast MRI in breast cancer care remains controversial. As part of a quality improvement initiative for breast cancer screening and treatment, we sent out a survey to physicians who treat breast cancer patients. All respondents are participants in the ATHENA initiative, a program which unites physicians, researchers, and patients at the five University of California medical centers.
Objective: To use the ATHENA infrastructure to perform a qualitative analysis of variations in breast cancer care.
Methods: Surveys were sent to 50 physicians in the ATHENA network whose practices are focused on breast cancer. Respondents were presented with clinical scenarios, and asked whether they would recommend MRI always/usually or sometimes/never. Differences were compared by Chi square.
Results: 39 physicians completed the survey (78% response rate). Of these physicians 29% were surgeons, 26% radiation oncologists and 45% medical oncologists. Athena physicians were more likely to order MRI for high risk screening of mutation carriers than not (85% yes vs. 15% no, p &lt; 0.003) but not based on breast density alone or previous history of breast cancer. They were also more likely to order it for monitoring neo-adjuvant chemotherapy (70% yes vs. 30% no, p &lt; 0.03). Although the majority answered that they would order a Breast MRI for new breast cancer the difference between responses was not significantly different (56% yes vs. 44%, p = 0.07).
Conclusion: Athena physicians follow established published guidelines which demonstrate a benefit for Breast MRI screening for BRCA mutation carriers but not based on density or previous history of breast cancer. The Athena network allows a forum for new practice guidelines to be implemented as data becomes available to improve patient outcomes and utilize the best evidence for patient care, where both the patterns of MRI use as well as the outcomes of practice patterns will be evaluated prospectively.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-13.
Abstract P4-01-16: Clinicopathological Factors that Predict the Accuracy of MRI in the Preoperative Setting.
Authors: Czechura Tomasz , Kantor Olga , Martz Brigid , Winchester David P , Winchester David J , Yao Katharine 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-16.
Abstract P4-02-05: A novel 64Cu-liposomal PET agent (MM-DX-929) predicts response to liposomal chemotherapeutics in preclinical breast cancer models
Authors: Lee H , Zheng J , Gaddy D , Kirpotin D , Dunne M , Drummond D , Allen C , Jaffray D , Hendriks B , Wickham T 
Published: August 2014

Abstract
Background: Liposomal anthracyclines (such as pegylated liposomal doxorubicin (PLD) or HER2-targeted liposomal doxorubicin (MM-302)) are being used and/or evaluated for the clinical management of breast cancer, but responses vary from patient to patient. It is hypothesized that variability in the deposition of liposomal therapeutics within tumors leads to differences in drug exposure, thereby directly influencing tumor response. We have developed MM-DX-929, a novel 64Cu-liposomal PET imaging agent, as a clinically-implementable tool to investigate whether image-based quantification of liposome deposition in tumors can predict treatment response to liposomal chemotherapeutics, including PLD, MM-302 and/or liposomal irinotecan (MM-398).
Objectives: Our primary objective is to demonstrate that the extent of tumor uptake of MM-DX-929 is predictive of tumor response to MM-302 in preclinical breast cancer xenograft models. A secondary objective is to enable clinical translation of MM-DX-929 to enable incorporation into existing therapeutic trials.
Methods: Mice bearing BT474-M3 mammary and subcutaneous tumors were injected intravenously with MM-DX-929 prior to dosing with MM-302. PET/CT imaging was performed at 16h post MM-DX-929 injection, and tumor uptake was determined. Response to treatment was quantified as tumor volume changes measured over a 2-month period by MRI.
Results: Tumor deposition of MM-DX-929 administration correlated well with treatment response to MM-302 (Spearman correlation coefficient of −0.891 and a p-value of 0.0004). MM-DX-929 accumulation in tumors prior to the start of the MM-302 treatment successfully predicted improved tumor growth inhibition following MM-302 treatment.
Conclusion: These findings support trials of MM-DX-929 as a predictive imaging agent to select patients who are most likely to respond to liposomal therapies. The clinical development of MM-DX-929 for identification of breast cancer patients likely to respond to liposomal therapeutics is currently being pursued.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-05.
Abstract P4-03-11: SUVmax of FDG-PET/CT is Associated with Chemotherapy Response Assay Test Results and Prognostic Factors in Breast Cancer Patients
Authors: Lee A , Chang J , Bang B , Lee J , Han D , Min S , Yun C , Kim BS , Lim W , Paik N , Moon B-I 
Published: August 2014

Abstract
Backgrounds:18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) is widely used for cancer evaluation and there are several studies which suggested maximum standard uptake value (SUVmax) may reflect the cancer patients' prognosis. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is commonly used as a chemosensitivity assay modality for the treatment of various cancers in clinical settings and there have been several studies on its usefulness in breast cancer. We previously reported chemosensitivity (ATP-CRA) results might reflect patients' prognosis. So we supposed that SUVmax could reflect chemosenitivity (ATP-CRA) results of patients, so performed this study to analyze the relationship between PET/CT SUVmax and chemosenstivity (ATP-CRA) results of these drugs. Furthermore, we evaluated prognostic factors for breast cancer according to SUVmax.
Materials and Methods: 102 breast cancer patients, who underwent PET/CT and chemosensitive (ATP-CRA) test between December 2010 and April 2012, were enrolled in this study. We analyzed, retrospectively, the correlation between SUVmax of PET/CT and chemosenitivity (ATP-CRA) results of doxorubicin/paclitaxel. SUVmax according to prognostic factors were also assessed.
Results: Chemosensitivity (ATP-CRA) results of doxorubicin and paclitaxel have significant positive correlation with SUVmax. Their correlation coefficient were 0.236 (p = 0.020) and 0.216 (p = 0.030), respectively. Patients with larger tumor size, higher histologic and nuclear grade, estrogen receptor negative, progesterone receptor negative, HER2 positive, and Ki67 positive (≥14%) have higher mean SUVmax values (p &lt; 0.05). In molecular subgroup analysis, triple negative group showed higher mean SUVmax values than luminal A group (p &lt; 0.001).
Conclusion: Higher SUVmax values of PET/CT is correlated with better chemosensitive (ATP-CRA) results of doxorubicin and paclitaxel, and poor prognostic factors of breast cancer. However, examination of additional cases might be needed.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-03-11.
Abstract P4-06-10: Epigenetic silencing of glutamine synthetase (Glul) defines glutamine depletion therapy
Authors: Cavicchioli F , Shia A , O'Leary K , Haley V , Crook TR , Thompson AM , Lackner M , Lo Nigro C , Schmid P 
Published: August 2014

Abstract
Background: Methylation-dependent transcriptional silencing of genes involved in amino acid synthesis can provide potential targets for novel synthetic lethality strategies. Glutamine synthetase (Glul) is the key enzyme in the biosynthesis of glutamine. We identified Glul as a novel gene subject to methylation-dependent transcriptional silencing in breast cancer cell lines using a combined functional screen with methylation reversal assays and methylation arrays.
Methods: Methylation reversal assays were performed using 5-aza-2-deoxycytidine and/or trichostatin treatment coupled with whole genome mRNA microarrays (Illumina HT-12 v4 Expression BeadChip Kit). Expression of Glul with and without pharmacological methylation reversal with azacytidine and/or trichostatin was validated using qRT-PCR and Western Blot. Methylation of Glul was analysed using methylation microarrays (Illumina 450K Methylation BeadChip), bisulphite sequencing and pyrosequencing. Sensitivity to glutamine deprivation was assessed using an MTT assay after culturing cells in media with various glutamine concentrations or in complete absence of glutamine. We used a panel of 55 breast cancer cell lines and formalin-fixed paraffin-embedded tissue from a series of 116 stage I-III primary breast cancers with linked mature clinical outcome data that were randomly selected from the Cuneo Tissue Bank. Tissue samples were subject to histopathological review to ensure adequate representation of cancer cells.
Results: Dense methylation of the CpG-island of Glul was detected in 45% of cell lines across all subtypes. Methylation of the CpG island was linked with absent or down-regulated expression of Glul in some but not all cell lines, and Glul expression could be reactivated by azacytidine and trichostatin in these cell lines. Methylation of shore areas was detected in several cell lines but was not associated with transcriptional silencing. Cells with methylation-dependent low or absent Glul expression were highly sensitive to glutamine deprivation, whereas cell lines without Glul methylation were rescued by compensatory up-regulation of Glul. Using pyrosequencing, dense methylation of the CpG island of Glul was found in 32.8% of patients, with an additional 17.2% of patients showing partial methylation. No significant association with a specific breast cancer subtype or outcome was found.
Conclusions: This is the first report of methylation-dependent transcriptional silencing of Glul expression in cancer. Our data demonstrate that a significant proportion of primary breast cancers show methylation of Glul and suggest that glutamine deprivation could be a novel synthetic lethality strategy for these cancers.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-10.
Abstract P4-06-14: CD146-suppresses breast tumor invasion via a novel transcription target TIMPv
Authors: Shanmuganathan S , AbdElmageed Z , Fernando A , Gaur R , Ramkumar A , Bhat S , Gupta I , Muzumdar S , Hakkim L , Ouhtit A 
Published: August 2014

Abstract
The function of the cell adhesion receptor CD146, a recently discovered marker of endothelial cells and a tumor promoter of melanoma and other cancers, is controversial in breast cancer (BC). However several lines of evidence supports its role as a tumor suppressor in BC. Further, the molecular mechanisms underpinning this suppression are unknown, neither has the ligand for CD146 been identified. Using a novel validated Enhanced Green Fluorescent Protein (EGFP)-inducible systems of CD146 expression both in vitro and in vivo, we provide here molecular and functional evidence of CD146 and its novel transcriptional target TIMPv (a variant of tissue inhibitor of metallo-proteinases) in underpinning the suppression of BC invasion.
Tetracycline (tet-on) CD146 system was developed in both MCF-7 and MDA-231 BC founder cell lines, and validated using time course RT-PCR and western blot analyses, and fluorescent microscopy. In functional experiments, induction of CD146 inhibited BC cell migration and invasion. TIMPv, the only endogenous protein inhibitor known for metallocarboxypeptidases, was identified by expression profiling as a novel transcriptional target of CD146-signaling, an association validated by quantitative PCR and immunoblotting experiments in a range of breast and melanoma cancer cells. However, siRNA inhibition of CD146 in the SKMel-28 melanoma cell line increased TIMPv expression, suggesting that while TIMPv is a positive transcriptional target of CD146 in BC cells, it is negatively regulated in melanoma cells. Furthermore, using invasion assay, the functional relevance of TIMPv to CD146-suppressed metastasis was demonstrated by selective suppression of TIMPv in CD146-expressing BC inducible cells using RNAi. More interestingly, induction of CD146 expression in vivo, using the tet-on CD146 expression system in BC Xenograft model resulted in suppression of breast tumor growth. Further, Clinical analysis of breast tissue samples by Immunohistochemistry showed that TIMPv expression patterns paralleled those of CD44s during breast tumor progression. Pharmacological and molecular approaches revealed that the activation of NFκB via Akt pathway couples CD146 to the transcription of TIMPv in BC cells.
Our study is the first report to provide a functional molecular link of a novel transcriptional target of CD146, TIMPv, to cancer via a unique axis that underpin CD146-suppressed BC progression; TIMPv is a potential target for guiding the development of novel therapeutic strategies for BC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-14.
Abstract P4-07-01: The Class I Selective PI3K Inhibitor GDC-0941 Enhances the Efficacy of Docetaxel in Human Breast Cancer Models by Increasing the Rate of Apoptosis
Authors: Wallin JJ , Guan J , Prior WW , Lee LB , Ross L , Belmont LD , Koeppen H , Belvin M , Sampath D , Friedman LS 
Published: August 2014

Abstract
Docetaxel (DTX) is commonly used as a front-line treatment option for breast cancer but many patients ultimately relapse and succumb to disease progression. Phosphatidylinositol 3-kinases (PI3K) are lipid kinases that regulate breast tumor cell growth, migration and survival. Given that phosphatidylinositol 3-kinase (PI3K) is frequently activated in breast cancer and induces chemo-resistance, it is an attractive target for combination therapy with standard of care drugs such as DTX. The current study was intended to determine if GDC-0941, an orally bioavailable class I selective PI3K inhibitor, enhances the anti-tumor activity of DTX in human breast cancer models in vitro and in vivo. A panel of 25 breast tumor cell lines representing luminal, HER2+ and basal sub-types were treated with GDC-0941, DTX or the combination of both drugs and assayed for cellular viability, modulation of PI3K pathway markers and apoptosis induction. The combination of GDC-0941 and DTX decreased the cellular viability of breast tumor cell lines in vitro but with variable drug synergy. The addition of both drugs resulted in stronger synergistic effects in a sub-set of tumor cell lines that was not predicted by breast cancer sub-type or mutations within the PI3K pathway. Human xenografts of breast cancer cell lines and patient-derived tumors were utilized to assess efficacy of GDC-0941 and DTX in vivo. In these models, the best combination efficacy was detected when the two drugs were dosed within 1 hour of each other. We also observed that GDC-0941 increased the rate of apoptosis in cells arrested in mitosis upon co-treatment with DTX. Our data provides a preclinical rationale for evaluating GDC-0941 in combination with DTX for breast cancer treatment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-07-01.