bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-12-11: Up-regulation of SPARC is associated with breast tumor progression and epithelial SPARC expression is correlated with poor survival and MMP-2 expression in patients with breast carcinoma
Authors: Lee JS , Kim G-E , Park MH , Yoon JH 
Published: March 2017

Abstract
Background: Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the process of tumor invasion and metastasis in many cancers. Matrix metalloproteinases (MMPs) degrade the extracellular matrix and participate in several key processes of invasion and metastasis. The aims of this study were to evaluate the potential involvement of SPARC in the progression of breast tumor and to determine its association with outcome variables and MMPs expression in patients with breast carcinoma (BC).
Materials and Methods: SPARC expression was examined in 8 pairs of BC tissues and surrounding normal tissues at mRNA and protein levels by quantitative real-time PCR (qRT-PCR), RNAscope in situ hybridization (ISH), Western blotting, and immunohistochemistry techniques. Immunohistochemical staining of SPARC on tissue microarray was done in 26 normal breasts, 76 ductal carcinoma in situ (DCIS), and 198 BC samples. In addition, we performed immunohistochemical staining for MMP-2 and MMP-9 in BC.
Results: SPARC expression at mRNA and protein levels by qRT-PCR and Western blotting was significantly increased in BC tissues compared to the surrounding normal tissues (p &lt; 0.05 and p &lt; 0.01, respectively). RNAscope ISH and immunohistochemistry of SPARC confirmed that SPARC expression was increased in BC tissues compared with their normal tissues and its expression was more pronounced in the stromal compartment than in epithelial compartment. SPARC expression was different among the normal, DCIS and BC groups and epithelial SPARC expression increased progressively from normal breast through DCIS to BC (p &lt; 0.001). In patients with BC, high epithelial SPARC expression was associated with worse disease-free and overall survival (p = 0.002 and p = 0.048, respectively) and independently predicted worse disease-free survival (p = 0.002). Epithelial SPARC expression was significantly correlated with MMP-2 expression (p &lt; 0.05).
Conclusion: Our results suggest that up-regulation of SPARC contributes to breast tumor progression. SPARC expression may be a useful biomarker for the prognostic prediction in patients with BC. SPARC can control extracellular matrix degradation through up-regulation of MMP-2.
Citation Format: Lee JS, Kim G-E, Park MH, Yoon JH. Up-regulation of SPARC is associated with breast tumor progression and epithelial SPARC expression is correlated with poor survival and MMP-2 expression in patients with breast carcinoma [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-11.
Abstract P4-12-14: Folate receptor alpha (FOLR1) expression in triple-negative breast cancer (TNBC)
Authors: Cui X , McIntire PJ , Ginter PS , Irshaid L , Chen Z , Shin SJ 
Published: March 2017

Abstract
Background Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in breast cancer. The limited studies evaluating the role of FOLR1 in breast cancer have shown that FOLR1 protein expression is enriched in triple-negative breast cancer (TNBC). Newly developed anti-FOLR1 therapy could potentially be used for patients with TNBC for whom few therapeutic options exist. We sought to evaluate FOLR1 protein expression in a cohort of patients with TNBC to determine its prevalence and prognostic value. Design Immunohistochemistry was performed for FOLR1 (26B3.F2, Biocare, RTU) on tissue microarray (TMA) slides consisting of 62 primary TNBC. Membranous staining in ≥5% of cells was deemed positive in a given case. Statistical analyses correlating FOLR1 protein expression with clinicopathologic parameters and clinical outcome [disease-free survival (DSF) and overall survival (OS) (range: 16 to 196 months, mean: 111 months)] were performed. Results 62 cases of primary TNBC from 61 patients were studied. All patients were female and the mean age was 55 years (range 30 to 91 years). Histologically, almost all tumors were invasive ductal carcinoma (94%; 58/62) and grade 3 (89%; 55/62). Most were pT1 tumors (71%; 44/62) or pT2 (27%; 17/62). For the majority of patients, the nodal status was N0 (61%; 38/62) or N1 (24%; 15/62) and the stage was 1 (53%; 33/62) or 2 (32%; 20/62). Most cases were negative for FOLR1 (84%; 52/62). FOLR1 expression did not correlate with any clinicopathologic parameters, DFS or OS (P&gt;0.05). Conclusion Similar to other studies, we found no correlation with FOLR1 expression and common clinicopathologic parameters and clinical outcome in TNBC. While FOLR1 expression has been previously reported to confer poor prognosis in breast cancer (all types), our findings suggest that in TNBC specifically, FOLR1 expression is not prognostically significant.
Citation Format: Cui X, McIntire PJ, Ginter PS, Irshaid L, Chen Z, Shin SJ. Folate receptor alpha (FOLR1) expression in triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-14.
Abstract P4-13-04: Efficacy of dipsacus asperoides (DA) in a model for triple negative breast cancer
Authors: Telang NT , Nair HB , Wong GYC 
Published: March 2017

Abstract
Background: The triple negative breast cancer (TNBC) is characterized by the absence of estrogen receptor-α (ER-α), Progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2). This molecular subtype responds only to conventional cytotoxic chemotherapy and to small molecule based targeted therapy. These therapeutic options are associated with long-term systemic toxicity and acquired tumor resistance leading to compromised efficacy. These limitations emphasize identification of efficacious non-toxic agents for secondary prevention/therapy of TNBC. Dipsacus asperoides (DA) is a Chinese herb of a nutritional nature. The root of this herb represents an ingredient that is commonly included in the traditional Chinese herbal formulations for health management purposes. The present study examines the growth inhibitory effects of DA and identifies possible mechanistic leads for their efficacy in a preclinical cell culture model for TNBC.
Experimental Model, Herbal Extract and Biomarkers: The human mammary carcinoma derived ER-α -, PR - and HER-2 - MDA-MB-231 cell linerepresents the model for TNBC. Non-fractionated aqueous extract from DA represents the test agent. Anchorage dependent growth, anchorage independent (AI) colony formation, cell cycle progression and relevant pathway specific mechanistic assays represent the quantitative biomarkers for efficacy.
Results: Treatment of MDA-MB-231 cells with DA extract induces a dose dependent cytostatic growth arrest (IC50: 0.0015%, IC90: 0.0030%), and strongly inhibits AI colony formation. Within the cytostatic concentration range, DA treatment inhibits cell cycle progression via progressive G2/M arrest, suggesting abrogation of the G2/M checkpoint affecting DNA damage repair pathway. The induction of cellular apoptosis by DA is indicated by a dose dependent up-regulation of pro-apoptotic Caspase 3/7 activity.
Conclusion: These data identify potential mechanistic leads for the efficacy of DA in the present model. The present study validates a mechanism based approach to prioritize efficacious non-toxic herbal extracts for secondary prevention/therapy of the TNBC molecular subtype of clinical breast cancer.
Citation Format: Telang NT, Nair HB, Wong GYC. Efficacy of dipsacus asperoides (DA) in a model for triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-13-04.
Abstract P4-18-03: Measuring what is important to patients in clinical trials: Hearing the patient's voice
Authors: Spears PA , Devine P , Finestone S 
Published: March 2017

Abstract
Patients who participate in clinical trials are important to clinical research and contribute to the advancement of medical discoveries. However, typical clinical trials do not always capture information that is important to patients: how they feel, function and survive. The only way to accurately measure how a patient feels or functions is to ask them. This can be done through the administration of health related questionnaires that are filled out by the patient without interpretation from anyone else; these are referred to as Patient Reported Outcomes (PROs). Although, PRO assessments have been used in clinical trials for the past 30 years through the collection of global quality of life (QOL) and later health related QOL (HR-QOL) measurements, the information has been too broad and has not been precise enough to use in drug approvals, descriptive drug label information or to inform other patients.
There is an effort to change the paradigm of PRO assessment to measure the information most relevant to patients in clinical trials. This includes measuring treatment toxicity, symptom burden and physical function. This is relevant information that other patients want to know about a specific treatment for a specific disease to help them in their treatment decision making. The voice of the patient is critical to assess these items, through PRO measurements. In order to ensure that PRO questionnaires are filled out during a clinical trial, there are ways to make them more acceptable to patients by involving patients in their development (what questions are asked/how many questions are asked/when they are given to patients/how they are given to patients). Patients can inform study teams on the acceptability, understandability and relevance of the questions being asked. Patients can be a key contributor to clinical trial development by identifying the questions that are most important to them and the best way to ask these questions during a clinical trial.
Patient advocacy and educational organizations like Cancer Information & Support Network (CISN) are advocating for changes in PRO collection in clinical trials. Based on information collected from many survivors, caregivers and advocates, a patient-centric clinical trial development model will be proposed. The model includes the involvement of patients as key stakeholders early in clinical trial development to incorporate PROs into clinical trials that are acceptable for patients to complete and the outcomes are meaningful and matter to future patients.
Citation Format: Spears PA, Devine P, Finestone S. Measuring what is important to patients in clinical trials: Hearing the patient's voice [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-18-03.
Abstract P4-18-05: Male breast cancer— infusing a little blue into the sea of pink
Authors: Wagner H , Boyages J 
Published: March 2017

Abstract
Male breast cancer (MBC) is a rare disease dominated by a sea of pink. Issues faced by men with this disease include delayed diagnosis, lack of male-specific information, stigma about having a "female disease" and often under-treatment.
MBC is often treated as a female breast cancer but differences between the two are starting to emerge. Men are often older at diagnosis and sometimes considered "too old" for more aggressive treatments such as chemotherapy. Drugs such as aromatase inhibitors may not be as effective in men as in women but are often prescribed. Drugs such as tamoxifen can cause side-effects such as weight gain, hot flushes, loss of libido and impotence.
Support for patients with MBC is less advanced than that for female breast cancer. A Man's Pink, a MBC advocacy organization, mission is to promote MBC awareness, increase early detection, optimize and increase the survival rates for men diagnosed with breast cancer. Male Breast Cancer: Taking Control (BC Publishing, Boyages, 2015) empowers patients to understand their diagnosis and treatment.
Apart from incidence data, prognosis and treatment options, this talk will focus on how a website (www.malebreastcancer.ca) dedicated to MBC can help dismiss some of the myths and help overcome stigmata for men facing difficulties at diagnosis, treatment and recovery.
Our goal is to promote awareness to assist with earlier diagnosis and treatment to improve survival rates and the journey for men in their battle with breast cancer.
Citation Format: Wagner H, Boyages J. Male breast cancer— infusing a little blue into the sea of pink [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-18-05.
Abstract P4-21-03: A randomized phase II study of Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer
Authors: Takahashi M , Nishiyama Y , Hara F , Naito Y , Baba M , Sasaki M , Sato M , Watanabe K , Uemura Y , Yamaguchi T , Mukai H 
Published: March 2017

Abstract
As for the HER2-positive breast cancer, there are many cases to be effective for neoadjuvant chemotherapy in comparison with other intrinsic subtypes. However, pCR is not provided by neoadjuvant chemotherapy in all cases. [Aim] This study evaluated the effectiveness of a therapeutic strategy that switches chemotherapy, based on Ki-67 tumor expression after initial therapy, relative to that of standard chemotherapy in patients with HER2-positive breast cancer. [patients and methods] Patients were randomly assigned to the control arm or the Ki-67 response-guided arm (Ki-67 arm). Primary tumor biopsies were obtained before treatment, and after three once-weekly doses of paclitaxel and trastuzumab to assess the interim Ki-67 index. In the control arm, paclitaxel and trastuzumab was continued for a total of 12 doses, regardless of the interim Ki-67 index. In the Ki-67 arm, subsequent treatment was based on the interim Ki-67 index. Early Ki-67 responders continued to received paclitaxel plus trastuzumab for a total of 12 doses, while early Ki-67 non-responders were switched to epirubicin plus cyclophosphamide every 3 weeks for three cycles with once-weekly trastuzumab for a total of 12 doses. The primary endpoint was the pathological complete response (pCR) rate. [Results] When 237 patients were enrolled, an interim analysis was conducted in 200 patients. There was almost linear correlation between the Ki-67 reduction rate at interim assessment and the pCR rate. The pCR rate in Ki-67 early non-responders in the Ki-67 arm (23.6%; 95% CI, 12.4 to 34.9) was inferior to that in the control arm (44.1%; 31.4 to 56.7; p=0.025). A strong correlation was not found between the Ki-67 reduction rate and the clinical response rate (Spearman's correlation coefficient 0.22).
pCR rate among Ki-67 early non-responders and responders TotalpCR nn%95%CIKi-67 early non responderControl arm59264431.4-56.7 Ki-67 response guided arm55132312.4-34.9Ki-67 early responderControl arm21104726.3-69.0 Ki-67 response guided arm2084018.5-61.5
Conclusions: The pCR rate in the Ki-67 arm was inferior to that in the control arm. A therapeutic strategy that switches chemotherapy, based on Ki-67 tumor expression after initial therapy, was not effective. The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer.
Citation Format: Takahashi M, Nishiyama Y, Hara F, Naito Y, Baba M, Sasaki M, Sato M, Watanabe K, Uemura Y, Yamaguchi T, Mukai H. A randomized phase II study of Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-03.
Abstract P4-21-21: Her2 is not a cancer subtype but rather a driver found in all intrinsic subtypes and highly enriched in molecular apocrine tumors
Authors: Daemen A , Manning G 
Published: March 2017

Abstract
Her2-enriched (Her2E) breast tumors defined by molecular profiling are discrepant from Her2-amplified tumors defined by clinical assessment – over half of all Her2-amplified tumors are not Her2E, while one-third of Her2E tumors are not Her2-amplified. We explored this discordance using genomic profiles of 4,000 breast tumors. We find clear support that Her2 amplification is a discrete cancer driver event and not a subtype, with little genomic impact other than in expression of genes on the amplicon. Many Her2-amplified tumors clearly belong to the basal, luminal A, or luminal B subtypes.
After accounting for the Her2 amplicon, most tumors classified as Her2E appear to be molecular apocrine, expressing high levels of androgen receptor and low to moderate levels of ER. The high rate of Her2 amplification in this group (63%) suggests that additional growth drivers are required for molecular apocrine tumors.
Her2 amplification is also a driver across subtypes of several non-breast tumor types. Her2 is amplified in 2% of 5,400 non-breast tumors, spanning 23 tumor types. The Her2 region in non-breast cancers shows a similar range of amplification and breadth of the amplicon, and a comparable rate of overexpression of genes within the amplicon for most Her2A tumors.
These discoveries reveal therapeutic opportunities for combining anti-Her2 therapy with endocrine or anti-androgen agents for breast cancer, and for expanding anti-Her2 therapy to other tumor types.
Citation Format: Daemen A, Manning G. Her2 is not a cancer subtype but rather a driver found in all intrinsic subtypes and highly enriched in molecular apocrine tumors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-21.
Abstract P5-03-06: Clinical value of 89Zr-trastuzumab PET in HER2-positive breast cancer patients with a clinical dilemma
Authors: Schröder CP , Bensch F , Brouwers AH , Lub-de Hooge MN , de Jong JR , van der Vegt B , Sleijfer S , de Vries EG 
Published: March 2017

Abstract
Background: Information on human epidermal growth factor receptor 2 (HER2) is essential for management of metastatic breast cancer (mBC). In patients suspected of HER2-positive mBC, standard work up may fail to clarify whole body HER2 status. We aimed to assess whether 89Zr-trastuzumab PET can support treatment decisions in patients posing this clinical dilemma.
Methods: 89Zr-trastuzumab PET was performed as described earlier (Gaykema et al, Clin Cancer Res 2014) in patients in whom standard work up with bone scan, FDG PET, CT and if feasible a biopsy, failed to evaluate HER2 status of their disease. 89Zr-trastuzumab PET was defined positive, when at least a dominant part of the tumor load showed substantial tracer uptake (Gebhart et al, Ann Oncol 2015), when tumor tracer uptake in single lesions (except brain) was ≥ normal liver uptake or when brain metastases had a tracer uptake &gt; background. Circulating tumor cell (CTC) analysis prior to tracer injectionwas performed using the CellSearch System (Janssen Diagnostics LLC) and CTC HER2 status was assessed immunofluorescently. Questionnaires about treatment decisions were completed before, directly after and ≥3 months after 89Zr-trastuzumab PET.
Results: Twenty patients were enrolled: 8 with two primary cancers (HER2-positive and HER2-negative BC or BC and non-BC), 7 with metastases inaccessible for biopsy, 4 with prior HER2-positive and HER2-negative metastases, 1 with primary BC with equivocal HER2 status (average 4.23 HER2 gene copies/nucleus). 89Zr-trastuzumab PET was positive in 12 patients, negative in 7 and equivocal in one patient. In 15/20 patients 89Zr-trastuzumab PET supported treatment decision. The scan altered treatment of 8 patients, increased physicians' confidence without affecting treatment in 10, and improved physicians' understanding of disease in 18 patients. Ten patients had 1-99 CTCs, 6 with HER2 expression. There was no correlation between HER2 expression by CTCs and 89Zr-trastuzumab PET results or subsequent treatment decision.
Conclusion: 89Zr-trastuzumab PET, but not CTC analysis, supports clinical decision making in BC patients in whom standard work up fails to evaluate HER2 status. (Funded by the Dutch A Sister's Hope).
Citation Format: Schröder CP, Bensch F, Brouwers AH, Lub-de Hooge MN, de Jong JR, van der Vegt B, Sleijfer S, de Vries EG. Clinical value of 89Zr-trastuzumab PET in HER2-positive breast cancer patients with a clinical dilemma [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-03-06.
Abstract P5-04-01: Cell cycle dynamics at single cell level dictates response to CDK4/6 inhibition
Authors: Asghar U , Barr A , Cuts R , Beaney M , Babina I , Sampath D , Lacap J , Crocker L , Young A , Nerukar A , Pearson A , Herrera-Abreu M , Bakal C , Turner N 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P5-06-09: Cyclin d1 binding to chromatin and the induction of chromosomal instability requires the fuzzy domain
Authors: Pestell RG , Di Sante G , Di Rocco A , Pupo C , Crosariol M , Tompa P , Tantos A , Wang C , Yu Z , Vadlamudi R , Mann M , Casimiro MC 
Published: March 2017

Abstract
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma (Rb) and the nuclear respiratory factor 1 (NRF1) proteins to regulate nuclear DNA synthesis and mitochondrial biogenesis. Cyclin D1 is required for oncogene-dependent growth and genetic ablation of the murine cyclin D1 gene resulted in resistance to Ras or ErbB2-induced mammary tumorigenesis and APC-induced gastrointestinal tumorigenesis. Cyclin D1 overexpression occurs in human breast, prostate, lung, and gastrointestinal malignancies and its abundance is induced at the level of transcription, translation and through post-translational modifications. Cyclin D1 plays a key role in transcriptional regulation inducing gene expression governing chromosomal instability (CIN) and cell-cycle progression. Cyclin D1 is also known to bind TF regulatory regions in chromatin immuno-precipitation (ChIP) assays. Genome wide analysis of cyclin D1 occupancy using ChIP-Seq identified binding sites including both the coding and non-coding genome with enrichment for genes regulating CIN and the G2/M phase (Top2A, AurkB, Cenpp, Mlf1ip, Zw10, Ckap2) consistent with enrichment of cyclin D1 at G2/M and the finding that cyclin D1 induces CIN. We sought to identify the molecular mechanisms governing the recruitment of cyclin D1 in the context of local chromatin to promote CIN. In order to define the domain of cyclin D1 involved in aneuploidy and tumorigenesis, we transduced and assessed the induction of aneuploidy in MEF cells using cyclin D1 wt (wt), cyclin D1 C-terminus domain (C4), cyclin D1 mutant lacking of the E-box motif (ΔE) or ctrl. We also searched for potential histone protein interaction motifs in cyclin D1 and determined the epigenetic motif recognized by cyclin D1 using a histone peptide array. The recognition of an epigenetic code by cyclin D1 may facilitate genome wide expression changes during cell-cycle progression and tumorigenesis. We finally identified a “fuzzy” domain of cyclin D1 which is required to local chromatin access for regulatory promoter regions governing and promoting CIN.
Citation Format: Pestell RG, Di Sante G, Di Rocco A, Pupo C, Crosariol M, Tompa P, Tantos A, Wang C, Yu Z, Vadlamudi R, Mann M, Casimiro MC. Cyclin d1 binding to chromatin and the induction of chromosomal instability requires the fuzzy domain [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-06-09.