bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-13-12: Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/ hepatitis B core antibody positive and/or hepatitis B surface antibody positive breast cancer patients who receive chemotherapy
Authors: Hattori M , Ito Y , Takahashi S , Fukada I , Iwase T , Iwata H , Hatake K 
Published: August 2014

Abstract
Background: Recently, chemotherapy-induced reactivation of hepatitis B virus (HBV) has been reported not only in patients positive for hepatitis B surface antigen (HBsAg), but also in patients negative for it. Although HBV reactivation is associated with substantial morbidity and mortality in patients undergoing cancer chemotherapy, the exact frequency and risk for HBV reactivation in HBsAg-negative breast cancer patients who receive chemotherapy remains unclear. In this study, we examined the frequency and risk for HBV reactivation in Japanese breast cancer patients who have received chemotherapy.
Methods: A total of 562 HBsAg-negative breast cancer patients received chemotherapy from June 2008 to May 2009 at the Cancer Institute Hospital of JFCR in Japan. Antibody to hepatitis B core antigen (anti-HBc) and antibody to hepatitis B surface antigen (anti-HBs) were screened for before chemotherapy in all patients. In patients who were positive for anti-HBc and/or anti-HBs, serum HBV-DNA levels were measured and monitored during and after chemotherapy.
Results: 93 (17.4%) HBsAg-negative breast cancer patients were found to have resolved hepatitis B (HBsAg-negative, anti-HBc-positive and/or anti-HBs-positive). One patient was found to be positive for HBV DNA before the initiation of chemotherapy and received adjuvant chemotherapy with Entecavir prophylaxis. 65 patients received chemotherapy in adjuvant or neoadjuvant setting, 28 patients received it for metastatic disease. In our monitoring period (median 15.3 months), no HBsAg-negative/ anti-HBc-positive and/or anti-HBs-positive breast cancer patients developed HBV reactivation during and after their chemotherapy.
Conclusions: A number of HBsAg-negative breast cancer patients have received chemotherapy with a risk for HBV reactivation; however, it has been determined that conventional chemotherapy regimens for breast cancer are unlikely to increase the risk of developing HBV reactivation in these patients.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-12.
Abstract P5-14-12: Cosmetic outcome is better after intraoperative radiotherapy compared with external beam radiotherapy: An objective assessment of patients from a randomized controlled trial
Authors: Keshtgar M , Williams NR , Corica T , Bulsara M , Saunders C , Flyger H , Bentzon N , Cardoso JS , Michalopoulos N , Joseph DJ 
Published: August 2014

Abstract
The randomised controlled TARGeted Intraoperative radioTherapy (TARGIT) Trial has demonstrated non-inferiority between the novel technique of TARGIT (intra-operative radiotherapy with Intrabeam ®) and conventional whole-breast external beam radiotherapy (EBRT) in women with early breast cancer, in terms of the primary outcome measure of risk of local relapse within the treated breast. As there are very low recurrence rates, cosmesis becomes an increasingly important outcome of breast conserving treatment with both surgery and radiotherapy. This study was performed to determine if the single high dose of TARGIT compared with EBRT leads to impaired cosmesis.
A validated, objective assessment software tool for evaluation of cosmetic outcome was used. Frontal digital photographs were taken at baseline (before radiotherapy) and annually thereafter for up to five years. The photographs were analysed by BCCT.core which produces a composite score based on symmetry, colour and scar.
A total of 342 patients were assessed, all over 50 years old with a median age at baseline of 64 years (IQR 59 to 68). The BCCT.core scores were dichotomised into Excellent and Good (EG), and Fair and Poor (FP). There were statistically significant increases in the odds of having an outcome of EG for patients in the TARGIT group compared with the EBRT group at year 1 (OR = 2.07, 95%CI 1.12 to 3.85, p = 0.021) and year 2 (OR = 2.11, 95%CI 1.0 to 4.45, p = 0.05).
This objective assessment of aesthetic outcome in patients from a randomised setting demonstrates that those treated with targeted intraoperative radiotherapy have a superior cosmetic result compared with those patients who received conventional whole-breast external beam radiotherapy.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-12.
Abstract P6-02-01: Elucidating the change of TRAIL sensitivity in basal like TNBC cell lines by lapatinib, and further therapeutic implication
Authors: Lim B , Dolloff NG , Allen JE , Dicker DT , El-Deiry WS 
Published: August 2014

Abstract
Triple negative breast cancer (TNBC) comprises 15-20% of breast cancer, and carries a poor prognosis. Recently, efforts to understand this heterogeneous group of cancers have led to recognition of different subtypes of TNBC by Dr. Pietenpol et al based on genetic and functional signature. So far, the only targeting agent for TNBC still remains as androgen receptor inhibitor for LAR group. Thus, other strategies in therapeutic development for TNBCs are necessary. TRAIL (Tumor Necrosis Factor-related apoptosis inducing ligand), a member of the TNF-alpha family of death receptor ligands, induces apoptosis by binding death receptors (DR4 and DR5), could be a good strategy in therapeutic development in TNBC. Unfortunately, majority of breast cancer cell lines are resistant to TRAIL targeted therapy especially basal like group of cells, as previously shown in the work of Lipkowitz at the NCI. Lapatinib, a well known as erbB 1 and 2 inhibitor had been found to have off target activity inducing JNK, an important activator of nuclear transcription of death receptor, and mitochondrial mediated intrinsic apoptosis pathway. Interestingly, study of combination therapy with lapatinib and TRAIL not only confirmed baseline poor sensitivity to TRAIL induced apoptosis in “basal like” HCC 1937 and MDA-MB-468 cell lines, but also revealed an unexpected difference in sensitization to TRAIL induced apoptosis by Lapatinib pre-treatment between these two cell lines. When treated with 48hrs Lapatinib high–dose treatment, HCC 1937 showed increased sensitization whereas MDA-MB-468 did not. Both HCC 1937 and MDA-MB-468 are in the same basal like 1(BL1) group by Dr. Pietenpol's analysis, and their baseline sensitivity to TRAIL inducing apoptosis are the same. In terms of apoptosis - there are two big categories of cells. Type I cells are independent of mitochondria for the induction of Fas death receptor mediated apoptosis, where as type II cells are mitochrondria-dependent. Thus we hypothesized that this difference in lapatinib induced TRAIL sensitization between two cell lines is due to difference in one being type I vs the other being type II cell, and this type of apoptosis is not likely equal in same subgroup of TNBC. If this hypothesis is correct, targeting apoptosis pathway in TNBC should incorporate the recognition of apoptosis cell types rather than functional/genetic based subtypes. We will further elucidate our hypothesis by studying JNK, caspase 3 and 9 activity and downstream of both intrinsic, extrinsic apoptosis pathway.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-02-01.
Abstract P6-04-13: Preclinical testing using a novel CT20p peptide-nanoparticle combination in breast cancer
Authors: Vishnubhotla PS , Boohaker RJ , Lee MW , Nemec KN , Santra S , Khaled AS , Perez M , Khaled AR 
Published: August 2014

Abstract
BACKGROUND: The marked difference in metabolism observed between tumor and normal cells could contribute to the development of invasive and metastatic forms of breast cancer. The problem is that while patients diagnosed with invasive forms of breast cancer may be initially responsive to treatment, a significant number develop relapsing and even metastatic disease. There is a critical unmet need to develop new therapeutic approaches for patients diagnosed with invasive forms of breast cancer that are effective given the unique metabolism of tumor cells. METHODS: We examined the cytotoxic properties of a novel peptide, CT20p, derived from the C-terminus of Bax. For delivery to cells, the amphipathic nature of CT20p allowed it to be encapsulated in polymeric nanoparticles (NPs). NPs were made using aliphatic hyperbranched polyester (HBPE) that incorporated surface carboxylic groups and interior hydrophobic cavities for encapsulation of CT20p. To examine the cytotoxic potential and targeting capacity of CT20p-HBPE-NPs, we treated MDA-MB-231 breast cancer cells and MCF-10A breast epithelial cells with the peptide-nanoparticle combination and measured changes in mitochondrial function, cell metabolism and induction of apoptotic and non-apoptotic cell death. The ability of CT20p-NP-HBPE to cause tumor regression was examined by subcutaneously implanting MDA-MB-231 cells in nude mice. RESULTS: Initial studies showed that CT20p caused the release of calcein from mitochondrial-like lipid vesicles, without disrupting vesicle integrity, and, when expressed as a fusion protein in cells, localized to mitochondria. While the peptide alone had little effect upon intact cells, likely not penetrating the plasma membrane, when encapsulated and delivered by nanoparticles, CT20p-HBPE-NPs proved an effective killer of breast cancer cells. CT20p-HBPE-NPs initiated non-apoptotic cell death within 3 hours of treatment by targeting mitochondria and deregulating cellular metabolism. Nanoparticles alone or nanoparticles encapsulating a control peptide had minimal effects. The cytotoxicity of CT20p-HPBE-NPs was most pronounced in breast cancer cells, sparing normal, epithelial cells. In implanted breast tumors, CT20p-HBPE-NPs accumulated in tumors within 24 hours and reduced tumor burden by 50-80%. CONCLUSION: These results reveal the innovative features of CT20p that allow nanoparticle-mediated delivery to tumors and the potential application in combination therapies that target the unique metabolism of cancer cells.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-04-13.
Abstract P6-04-14: mRNA expressions of lamin B1 and lamin B receptor: Clinical correlations with human breast cancer
Authors: Wazir U , Ahmad MH , Bridger JM , Harvey A , Jiang WG , Sharma AK , Mokbel K 
Published: August 2014

Abstract
BACKGROUND: Lamin B (LMNB) and lamin B receptor (LBR) are key components of the nuclear envelope, with roles in chromosomal stability, DNA repair, and cell differentiation. Lamins provide structural support to the nuclear envelope, while LBR is believed to anchor lamin B to the envelope. In addition, LBR also has a number of downstream mediators which affect cell cycle and cell differentiation.
Classically, they have been implicated in a spectrum of largely congenital ailments including certain forms of muscle dystrophy and progeria. These conditions are collectively referred to as “laminopathies”.
More recently, defects in the expression of lamins have been implicated in neoplasias of the colon, prostate, liver and ovaries.
In this study, we have endeavoured to elucidate the relationships between the mRNA expressions of LMNB1 and LBR and the clinicopathological parameters of human breast cancer.
METHODS: Breast cancer tissues (n = 115) and associated non-cancerous tissue (ANCT) (n = 30) underwent reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data.
RESULTS: LMNB1 mRNA expression was higher in ANCT as compared to cancerous tissue (ANCT vs. cancerous tissue: 0.12 vs. 0.00; p = &lt;0.0001). This difference remained highly significant in all patient categories by tumour grade and clinical stage.
In addition, the expression of LMNB1 declined with worsening clinical outcome. This association was statistically significant when comparing patient with disease-free survival with disease related mortalities (Disease-free vs. mortalities: 0.0011 vs. 0.000; p = 0.0177).
LBR mRNA expression was found to be directly associated with tumour grade (grade 1 vs.3: 0.00 vs. 0.00; p = 0.0479) and the Nottingham Prognostic Index (NPI1 vs. 3: 0.00 vs. 0.00; p = 0.0551).
CONCLUSIONS: To our knowledge, this is the first study to suggest such a role for LMNB1 and LBR in human breast cancer.
The contrasting relationships of LMNB1 and LBR expressions with the clinicopathological parameters of human breast cancer may suggest that disruptions in the physiologically normal interactions between these molecules in the nuclear envelope may serve as pathway leading towards the pathogenesis of human breast cancer. Potentially this may be a significant pathway requiring further investigation to be better understood, in order to identify further potential areas for therapeutic intervention.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-04-14.
Abstract P6-05-12: Comprehensive molecular analysis of estrogen receptor positive breast cancer to determine clinically actionable alterations
Authors: O'Brien C , Savage H , Huw L , Fumagalli D , Salgado R , Criscitello C , Pugliano L , Laios I , Piccart M , Michiels S , Sotiriou C , Loi S , Lackner MR , Wilson TR 
Published: August 2014

Abstract
Introduction.
Understanding the genetic landscape of estrogen receptor positive breast caner is critical for defining clinically actionable alleles that may be targeted using next generation biologics. PIK3CA mutations have previously been reported to be the most common mutation within estrogen receptor positive breast cancer, however the overlap and mutual exclusivity with other key driving alleles is poorly understood, especially how these biomarkers change following treatment failure. We custom designed a mutation, copy number variation and RNA expression panels to profile biomarkers from low quality formalin fixed paraffin embedded extracted material. Data relating to key pathways, such as PI3K and immune modulatory pathways, and overlap with other biomarkers will be presented.
Methods.
Formalin fixed paraffin embedded material was available from 195 primary cases and 95 paired metastatic estrogen receptor positive breast cancer patients. Samples were assayed for the expression of PTEN by IHC, hotspot mutations in 11 oncogenic driving genes using Q-PCR based technology, copy number alterations in 42 genes using Q-PCR based technology and RNA expression using a custom designed 400 breast cancer specific NanoString gene panel.
Results.
PTEN loss, as defined by H-score of 0, was found in 4.5% of primary samples and in 4.3% of metastatic samples. PIK3CA mutations were found in 43% of primary samples and in 38% of metastatic samples and were largely found to be mutually exclusive with PTEN loss. AKT1 mutations were found in 5.4% of primary samples and in 4.1% of metastatic samples. Less frequent mutations in KRAS (7.0%) and BRAF (1.7%) were found in the primary sample, and some were co-existing with PIK3CA mutations. Copy number gains were found in CCND1 (23.5%), ZNF703 (19.5%), FGFR1 (16.8%) and PAK1 (11.4%) and were largely concordant with the paired metastatic sample. Analysis with clinical outcome is ongoing.
Conclusions.
PIK3CA was the most frequently altered gene detected and was mutually exclusive with other key driving mutations within the PI3K pathway (AKT1 and PTEN). A strong concordance was observed between genetic alterations found in the primary sample and the paired metastatic sample. Mutations and expression gains within clinically actionable targets were found less frequently, but may provide alternative treatment strategies for these patients following failure of endocrine therapy.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-12.
Abstract P6-05-18: A53, cell cycle phenotype and Cdc7 kinase: Identifying patients likely to benefit from targeted Cdc7 therapy
Authors: Ian P , Leigh E , Fizza M , Kai S , Gareth WH , Richard S 
Published: August 2014

Abstract
We previously reported multiparameter analysis of cell cycle regulatory proteins in breast cancer and identified three prognostic ‘cell cycle phenotypes’. Phenotype iii represents cells traversing through the mitotic cell division cycle and is associated with poor prognosis and high Cdc7 levels1. Cdc7 kinase initiates DNA synthesis at chromosomal replication origins and is rate-limiting for S phase entry. In cell-based studies we discovered a new, p53-dependent cell cycle checkpoint which reversible arrests normal cells in G1 phase if DNA replication initiation is perturbed. In cancer cells treated with Cdc7 inhibitors this checkpoint function is lost, resulting in aberrant S phase entry and subsequent apoptotic cell death2,3. Cdc7 kinase is therefore emerging as a novel therapeutic target in cancers bearing mutant p53.
In this study we investigated whether the inclusion of p53 mutation status adds further prognostic power to the cell cycle phenotype. We also questioned whether p53 mutant breast cancers express high Cdc7 levels and are thus more likely to be of cell cycle phenotype iii (susceptible to Cdc7-targeted therapy).
Our results show that Cdc7 levels are inversely correlated with p53 mutation status (n = 173) and are highest in cell cycle phenotype iii and harder to treat Her-2 and triple negative breast cancer subgroups. Cell cycle phenotype is the strongest predictor of early relapse compared to p53, Ki67 and Cdc7 on univariate analysis and remains so on multivariate analysis after adjusting for p53 status (HR = 3.80, p = 0.002).
These findings support the supposition that p53 negatively regulates Cdc7 expression. Combined testing for p53 status, cell cycle phenotype and Cdc7 expression identifies those patients with breast cancer most likely to benefit from targeted therapy with Cdc7 inhibitors.
1 Br J Cancer. 2009 Mar 24;100(6):959-70
2 EMBO J. 2010 Oct 6;29(19):3381-94
3 Am J Pathol. 2010 Oct;177(4):2034-45.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-18.
Abstract P6-05-22: Young-onset breast cancer exhibits a more aggressive tumor biology
Authors: Cabioglu N , Bozdogan A , Eren-Boler D , Kara H , Karayagiz H , Uras C 
Published: August 2014

Abstract
Objective: Previous studies demonstrated poorer survival in patients with young-onset breast cancer. Therefore, we investigated the distinguishing molecular characteristics associated with young onset breast cancer.
Material and Methods: Between September and February 2013, 506 patients with breast cancer, who underwent surgery at our institution, were retrospectively analyzed tailored by age ≤40 (n = 94; 18.6%) and &gt;40 to determine clinicopathological and biological differences. Therefore, molecular subtypes were determined by immunohistochemistry for ER, PR, Ki67, and HER2-neu.
Results: The median age was 50 (27-87). Patients aged ≤40 presented with more advanced disease (stage III/IV; 34% for ≤40 vs 20% for &gt;40, p = 0.003). Among patients, who underwent surgery as initial treatment (n = 411), patients ≤40 were more likely to have or tumors with invasive ductal carcinoma type (p = 0.049), or tumors &gt;20 mm (p = 0.033), or axillary positivity (p = 0.003), or with multifocality/multicentricity (p&lt;0.001), or with high nuclear grade (p = 0.019), or with histological grade (p = 0.023), or lymphovascular invasion (p = &lt;0.001), higher Ki-67 expression (%15≤) rates (p = 0.014), or lower luminal A rates (luminal-A vs other; p = 0.04) compared with patients aged &gt;40. Furthermore, logistic regression analyses revealed presence of multifocality/multicentricity (OR:2.6; 95% CI: 1.4-4.5; p = 0.001), lymphovascular invasion (OR:2.1; 95% CI: 1.2-3.6; p = 0.008), and molecular subtype other than luminal A (OR:2.4; 95% CI: 1.1-5.1; p&lt;0.001) were significant features that were associated with breast cancer aged ≤40.
Conclusion: Our results suggest that tumors of patients with younger age exhibit a more aggressive biology compared to patients older than 40 as shown by molecular subtype analyses that could result in poor prognosis.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-22.
Abstract P6-06-42: Impact of molecular subtype on overall survival according to age in Korean women
Authors: Lee A , Woo J , Yun C , Min SY , Kim Y , Yu S , Lim W , Paik N-S , Moon B-I 
Published: August 2014

Abstract
Introduction: Breast cancer is a heterogeneous diseases, which is based on expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Using these factors, molecular subtype can be determined as luminal A, luminal B, HER2+, and TNBC. This is considered as an important prognostic factor. In breast cancer, age is the one of the important prognostic factors and prognosis is varied according to patients’ age. We performed this study to analyze the impact of molecular subtypes on prognosis of breast cancer according to patients’ age.
Patients and methods: We performed this study by using Korean Breast Cancer Society Registration Program data. Total 15,286 patients are included into this study, and they underwent surgery during the period Jan. 2001 to Dec. 2006. All patients were divided into two groups according to age (younger: age≤34, older: age≥35) and molecular subtypes were classified into four groups as follows: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+ HER2+), HER2+ (ER-, PR-, HER2+), and triple-negative (ER-, PR-, HER2-). We determined prognostic impact of molecular subtype on overall survivals (OS). Clinicopathologic results and OS were compared by chi-square test, Kaplan Meier test, and Cox's hazards model.
Results: Younger group more frequently had tumors with negative hormone receptor (ER-/PR-), worse prognostic factors and diagnosed with more advanced stage compared to older group. In univariate analysis, molecular subtype was not related with OS in younger group (p = 0.069), but not in older group (p&lt;0.001). In multivariate analysis, molecular subtype was an independent prognostic factor for OS only in older group (p = 0.690 vs p&lt;0.001).
Conclusion: In young breast cancer patients, less than 35 years, the impact of molecular subtypes on overall survival was not significant compared to other age group.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-42.