bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of genetic predisposition to lymphedema.
Authors: Armer J. M. , Stewart B. R. 
Published: February 2017

195 Background: In the United States, 203,000 women are diagnosed annually with breast cancer (BC). Currently, over 2.3 million women in the United States are breast cancer survivors. With the increased incidence and survivorship, more women are living with the long-term treatment effects such as lymphedema (LE). We are nearing completion of stage one of a three-stage research project to examine genetic factors that potentially predispose BC survivors to develop LE. In stage one, we are working to identify novel genetic polymorphisms pointing to genomic regions and genes associated with LE risk. In stage two, we will use exome sequencing to examine both rare and common genetic variants potentially associated with variation in symptom manifestations of LE in breast cancer survivors; to examine phenotypic and genotypic variation in LE emerging following cancer treatment; and to examine associations between LE phenotypes among breast cancer survivors with LE and genomic factors and non-genomic factors. In stage three, we will replicate at the genetic level the associations detected. Methods: Institutional funding was obtained for a GWAS-design feasibility study with 96 breast cancer survivors with and without LE (48/48). Genetic material (from buccal swabs), limb volume (by perometry and circumferences), and self-reported LE-related symptoms were collected in one laboratory appointment. Results: Ninety-five percent of survivors participating in an on-going longitudinal study consented to participate in the genetic pilot (N=96). Buccal swabs provided yield for DNA extraction (concentration average 174.94 ng/ul). An additional 96 specimens have been collected for a second pilot GWAS (N =192). Conclusions: The pilot findings form the basis for a larger multisite proposed study to examine genetic predisposition to secondary LE. The findings of the larger study will lead to the design and timing of subsequent interventions aimed at reducing LE risk and improving overall survivorship quality of life. Findings concerning interactions among best cancer treatments and LE genetic predisposition will have the potential to guide the selection of cancer treatment to minimize complications when survival outcomes are equivalent across competing treatment approaches.
Results of a pilot study of a web-based care plan to meet the communication needs of breast cancer survivors and their primary care physicians.
Authors: Haq R. , Leung F. H. , Dastur D. , Baker N. A. , Heus L. , Li B. , Parsons J. A. 
Published: February 2017

200 Background: Following treatment, breast cancer patients (BCPs) can feel “lost in transition”. Family practitioners (FP) also report feeling ill-equipped to provide follow-up care to breast cancer patients. In this 3-phase qualitative pilot study we designed, implemented and evaluated a multi-faceted care plan (MCP) to address the information/communication needs of BCPs and their FPs. Methods: We first conducted focus groups and interviews with 35 participants from 3 stakeholder groups (BCPs, FPs and oncology team), to identify specific information and communication needs. A MCP was designed based on these findings. The MCP was then evaluated via focus groups and interviews with 26 participants. Interviews and focus groups were audiotaped, transcribed and content analysed for emergent themes and patterns. Results: Pre-implementation, participants identified communication needs pertinent to BCPs and FPs. Patients commented that web-based, paper-based and human resources components are essential to any care plan. Patients did not focus solely on the post-treatment period, but rather spoke of evolving needs throughout their cancer journey. FPs indicated that any tools to support them must distill important information in a readily accessible and easy-to-use format. Based on this needs assessment, a MCP was designed and implemented for BCPs and FPs. This consisted of tailored websites, as well as paper-based care plans and a patient booklet. Patients provided positive feedback about the MCP, indicating that it was effective at addressing many of their needs and commented “I wish I’d had this before”. Suggestions for future improvements to the MCP included greater emphasis on health-and-wellness post-treatment. In addition, some patients voiced resistance to the terms “survivor” and “survivorship” in materials, as they did not self-identify with such terms. Conclusions: This MCP shows promise in addressing the information/communication needs of BCPs and FPs who care for them. Next steps include tool refinement, further evaluation, and planning for more extensive implementation.
Probably benign findings, BIRADS category 3 (MR-Bi3), on magnetic resonance imaging of the breast (BrMR): Is repeated MRI an alternative to biopsy?
Authors: Janicek M. J. , Camaya V. M. 
Published: February 2017

21 Background: The shift from the use of BrMR for confirmation of known abnormality to the screening mode in problematic breast is associated with higher frequency of probably benign findings. Some of them still require biopsy, with or without close BrMR follow up (f/u), some may remain on observation only. Our pilot study analyzed clinical outcomes of MR-Bi3 pts and added value of close BrMR f/u. Proportion of MR-Bi3, some after “second look ultrasound” (2ndUS) with or without biopsy could be used among other monitors of BrMR practices. Methods: We reviewed BIRAD categories assigned to all 743 BrMRs done in period of year 2007 in our specialized breast imaging practice with dedicated BrMR (Aurora) system and full complement of diagnostic and interventional modalities. Frequency of MR-Bi3 and studies resulting in MR-Bi3 or biopsies after 2ndUS were analyzed. With benefit of 3 year clinical data, the outcome of patients on such short term f/u schedule was reviewed. Results: MR-Bi3 was assigned to 40 (5.4%) of our BrMRs on the initial evaluation, all of them yielded benign findings on follow up. Additional 26.2% of our studies required 2ndUS. After 2ndUS, 40% of these pts were converted to Bi4+5, continued with image guided biopsy with cancer detected in 35% of those. Remaining 60% of 2ndUS yielded “probably benign findings”, MR-Bi3, which means that total of 21.6% of our BrMRs remained on close f/u schedule with MRI. There were no additional delayed findings of malignancy in this group. Single additional BrMR was sufficient to confirm benign findings only in 47% of cases, 24% of patients required multiple BrMRs at 6 month intervals, remaining patients were followed by other modalities. Conclusions: Utilization of MR-Bi3 category reflects readers' confidence avoiding or justifying biopsies for border line findings. Targeted use of 2ndUS helps to identify patients who benefit from biopsy rather than close f/u. Proportion of repeated Bi3 and outcome of Bi3 could become valuable QA indices for monitoring of BrMR practices. Only in small proportion of cases, the use of Bi3 was not contributory, particularly in case of repeated BrMRs for the same abnormality.
Relationship between lack of patient compliance with adjuvant therapy guidelines and recurrence in early breast cancer.
Authors: Citrin D. L. , Neelam R. , Grutsch J. F. , Mortensen S. J. 
Published: February 2017

215 Background: Modern treatment (Tx) of early stage breast cancer (BC) often requires a combination of surgery, radiation and adjuvant drugs (chemotherapy, hormones and/or Herceptin). Lack of patient compliance is often an issue, due to the prolonged nature of Tx and lack of perceived benefit when there is no clinically overt disease. Methods: We retrospectively evaluated consecutive patients with recurrent BC who had primary Tx for stage I-III BC elsewhere, and were seen at MRMC over an eighteen month period by DLC or RN following relapse. Patients with stage IV or inflammatory BC at initial diagnosis were excluded. All patients in this study were therefore considered failures of primary Tx. Results: A total of 215 patients (median age 44, range 27-74) were included in this study. Sites of recurrence were loco-regional 73, distant mets 117, both 25. 215 (60%) were found to have had inadequate Tx as per NCCN guidelines. The most common deviations from NCCN guidelines were due to patients’ refusal of chemotherapy or hormone therapy. Detailed information about nodal status was available for 208 patients (see table). The proportion of patients with 0-3 nodes positive who received inadequate primary Tx was statistically significantly greater than the proportion of patients with > 3 nodes involved (Pearson Chi Square p < 0.0001). Conclusions: This retrospective study suggests that patient compliance is a key factor in determining efficacy of primary Tx of early BC. [Table: see text]
Methylation RE in serum of patients with breast cancer and relation with molecular phenotype and worse prognostic factors.
Authors: Martínez-Galan J. , Torres-Torres B. , Del Moral R. , Núñez M. I. , Ríos S. , Ballesteros P. , Delgado J. R. 
Published: February 2017

224 Background: To determine whether Estrogen Receptor (ESR1) (+) and ESR1(-) status relates to epigenetic changes in breast cancer-related genes and to correlate with molecular breast cancer subtypes. Methods: Since January/02 to June/05, we quantified methylation levels ERS1 gene in serum of 92 pts breast cancer. A PCR quantitative technique was used to analyze levels of methylation gene. We also examined and correlationed the expression of ESR1 in tumors by immunohistochemistry with molecular phenotype. Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement (N0; 63%, N1; 30%, N2; 7%), tumor size (T1; 58%, T2; 35%, T3; 4%, T4; 4%) and grade (G1; 20%, G2; 37%, G3; 30%). Of the cases, 37 pts (40%) were Luminal A (LA), 32 pts (33%) Luminal B (LB), 14 pts (15%) Triple-negative (TN) and 9pts (10%) HER2+. The methylated ESR1 in serum was significantly associated with ESR1(-) in breast tumors >80% (p=0.0179). Methylation ESR1 was preferably associated with TN (80%) and HER2+ (60%) subtype. Nevertheless unmethylation ESR1 was found more frequently in LA (71%) and LB (59%) phenotype. With a median follow up of 5 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene (p>0.05), Luminal A; ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B; ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative; ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2; ESR1 Methylation SG at 5 years was 66.7% vs 75% unmethylation ESR1. Conclusions: Gene promoter region hypermethylation is a significant event in primary breast cancer. However, its impact on tumor progression and potential predictive implications remain relatively unknown. Our study identifies the presence of variations in global levels of methylation promoters ESR1 genes in breast cancer with different phenotype classes and shows that these differences have clinical significance. Although numerous issues remain to be resolved, quantitative measurement of circulating methylated DNA may be of significance in the assessment and search of targeted therapy resistance related to ESR1 and HER2 status by epigenetic or transcriptional cancer therapy.
SmgGDS splice variants: Potential novel targets for breast cancer therapeutics.
Authors: Bergom C. , Hauser A. , Lorimer E. L. , Li R. , Mackinnon A. C. , Williams C. L. 
Published: February 2017

225 Background: Breast cancer malignancy is promoted by the small GTPases K-Ras, Rap1, RhoA, and Rac1. We recently reported that the activity of these GTPases is regulated by two splice variants of SmgGDS, named SmgGDS-558 and SmgGDS-607. SmgGDS is overexpressed in lung and prostate cancer, but its role in breast cancer is unknown. Here we examine whether SmgGDS splice variants are expressed in breast cancer and promote breast cancer malignancy. Methods: Immunohistochemical staining for SmgGDS was performed on archival human breast tumors (N=183) and normal breast tissue (N=22). Immunoblotting was used to detect SmgGDS splice variants in human breast cancer cell lines. siRNAs that silence different SmgGDS splice variants were used to examine the effects of SmgGDS knockdown on breast cancer cell spreading, cell proliferation via [3H]thymidine uptake, anchorage-independent cell growth using soft agar colony assays, and NF-kB activation using luciferase reporter assays. Results: SmgGDS expression was detected in >65% of DCIS and invasive lobular and ductal carcinoma, and in 100% of metastatic tumors, but was detected in only 18% of normal breast tissue specimens (p<0.01). All tested cell lines expressed both SmgGDS splice variants. Silencing SmgGDS-558 or SmgGDS-607 with siRNA significantly diminished cell proliferation (100±2.0 vs. 11.3±1.0 vs. 50.5±2.2, p<0.05) in MCF-7 cells, with similar results in MDA-MB-231 and T47D cells. MCF-7 soft agar colony formation was significantly decreased 71% and 49% when SmgGDS-558 or SmgGDS-607 was silenced. MCF-7 cell spreading was promoted by silencing SmgGDS-558, but not SmgGDS-607. NF-kB activation was also decreased by 30% in resting and TNF-α-treated MCF-7 and MDA-MB-231 cells by silencing either splice variant. Conclusions: SmgGDS is disproportionally expressed in human breast cancers. Reduction of SmgGDS-558 and SmgGDS-607 levels dramatically reduced breast cancer cell proliferation, soft agar colony formation, and NF-kB activation. Our results indicate that SmgGDS splice variants regulate breast cancer malignancy, most likely through their regulation of small GTPases. This study identifies SmgGDS splice variants as novel therapeutic targets in breast cancer.
Metastatic breast cancer detection and therapy monitoring using folate-targeting flow cytometry.
Authors: Hong B. , Mace M. , Crowder R. , Coleman T. , He W. , Szczepanski F. , Feczko J. , Lyzak J. 
Published: February 2017

23 Background: Circulating tumor cell (CTC) has emerged as a valuable surrogate tumor marker for cancer diagnosis, prognosis, therapy personalization, and drug discovery. To identify CTCs, EpCAM and/or cytokeratin have been commonly used; however, their expression may diminish for subgroups of breast cancers or during epithelial-mesenchymal transition. A unique approach by targeting folate receptor (FR) on CTCs overcomes the limitation. Cancer cells overexpress FR with high affinity (KD=0.1 nM) to internalize high levels of folate for rapid growth. FR is also found upregulated in most cancers, while at very low levels in normal tissues. Methods: A flow cytometry based in-vitro CTC assay kit (OncoIVDx) was developed by IV Diagnostics Inc to specifically enumerate CTCs which overexpress FRs. 20 mL of 9 metastatic breast cancer (MBC) patients' peripheral blood was collected using CellSave tube before and after the treatment in midst of therapy. CTCs were tagged by fluorescently labeled folate conjugate, while leukocytes were counterstained by anti-CD45. To absolutely count the rare CTCs, a fluorescent bead was added serving internal control. Results: Table. Conclusions: No obvious shift in dot plots was found for patients' leucocytes compared to those in normal sample. Tumor size, histologic grade, nodal involvement and lymphovascular invasion (LVI) did not display a significant association with CTC presence, although more positive nodes with identified LVI might indicate an unfavorable increase in CTC counts. CTC presence was found associated with serum marker CA27.29. A score of 30 and less correlated with CTC response to the treatment. Chemotherapy alone or in combination with hormone therapy did not correlate with the change in CTC counts after treatment, except for hormone therapy alone. Unfavorable progression of cancers could be predicated for the patients with approximately 25 and more CTCs. We would like to thank NIH/NCI for SBIR phase I grant (1R43CA13789301A1). [Table: see text]
Barriers to screening and treatment of breast cancer: Data analysis from Edgecombe County.
Authors: Picton M. E. , Ramirez B. , Liles D. , Sastry T. R. , Petruzziello M. 
Published: February 2017

232 Background: Edgecombe County in NC was described as the 3rd highest location breast cancer mortality according to the Susan G. Komen report (2007). The major issues detected were low education, lack of healthcare providers, and large numbers of uninsured individuals. Our analysis sought to further characterize the circumstances unique to this region and measures to improve mortality. Methods: Between October 2008 and January 2009, 493 surveys were conducted throughout the county. The surveyors randomly approached female residents of Edgecombe County who completed a questionnaire, which was analyzed for this study. Results: Of the total population 354 women were older than age 40. In this group 82.5% had recent mammograms and 79.8% clinical breast examinations. Also, 91.7% had a Primary Physician who recommended mammograms in 85% of the cases. Only 27.1% had family history of breast cancer and, of those, 86.2% were recommended mammograms. Most were educated (58.6%), had low income (76%) and health insurance (87.4%). Nearly equal numbers of Caucasians and African Americans completed the survey (50.6% vs. 47.6%). Just 8.1% had transportation problems and 3.6% were aware of free mammograms in the health department. Statistical analysis by the Fisher’s Exact Test evaluated the relationship between the likelihood of having a screening mammogram and different variables. Women who attended church were more likely to undergo mammograms (p=0.00054), as were women with insurance (p=0.024). Family histories of breast cancer, lack of transportation, low income or deficient education were not significant determinants to obtain a mammogram. A logistical regression model demonstrated that attendance to church and insurance were the two factors statistically significant in terms of obtaining a mammogram. Conclusions: The main issues identified by our analysis were low-income, low health care literacy and lack of awareness regarding breast cancer programs. Our results were discordant with some of the Susan Komen report data, particularly that the majority of participants had a mammogram. Transportation and religious beliefs were not barriers to screening of breast cancer.
The effect of tumor subtype on survival and the graded prognostic assessment (GPA) for patients with breast cancer and brain metastases.
Authors: Sperduto P. W. , Kased N. , Roberge D. , Shanley R. , Chao S. T. , Bhatt A. K. , Brown P. D. , Shih H. A. , Kirkpatrick J. , Gaspar L. E. ,   Graded Prognostic Assessment \(GPA\) Consortium
Published: February 2017

238 Background: The Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast GPA by analyzing a larger cohort and tumor subtype. Methods: A multi-institutional retrospective database of 400 breast cancer patients treated for newly-diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression (MCR) and recursive partitioning analysis (RPA). Factors were weighted by magnitude of their regression coefficients to define the GPA index. A GPA score of 4.0 represents the best prognosis, 0.0, the worst. Results: Significant prognostic factors by MCR and RPA were Karnofsky Performance Status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60-80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0 was 3.4 (n=23), 7.7 (n=104), 15.1 (n=140) and 25.3 (n=133) months, respectively (p < 0.0001). See table. Among HER2-negative patients, being ER/PR-positive improved MST from 6.4 to 9.7 months whereas in HER2-positive patients, being ER/PR-positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA versus 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision-making and stratification of clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone. [Table: see text]
Impact of eribulin on overall survival in patients with metastatic breast cancer with visceral disease.
Authors: Vahdat L. T. , Cortes J. , Twelves C. , Wanders J. , Seegobin S. , Dutcus C. , O'Shaughnessy J. 
Published: February 2017

239 Background: Visceral disease is associated with poor survival outcome in women with metastatic breast cancer (mBC). Eribulin mesylate is a nontaxane microtubule dynamics inhibitor indicated for 3rd-line monotherapy in patients (pts) with mBC previously treated with at least two chemotherapeutic regimens in the metastatic setting, including an anthracycline and a taxane. Methods: Evidence from the global, randomized, multicenter, phase III clinical trial of eribulin in mBC (EMBRACE) demonstrated improved overall survival (OS) for eribulin-treated pts when compared to treatment of physician’s choice (TPC). In this unplanned subgroup analysis, we compare the clinical benefit of eribulin to TPC in mBC pts with visceral disease using the Independent Review database. Patients were categorized as having visceral disease if they had target or non-target lesion involvement in the adrenal gland, liver, lung, pleural, pericardial/peritoneal cavity, spleen, or thyroid. Patients with brain metastases were excluded from the trial. Results: EMBRACE enrolled 762 pts with mBC, with single organ disease present in 120 pts (15.7%). The remaining pts had multi-organ disease. A total of 81.9% (624) of pts were classified as having visceral disease–81.3% (413) randomized to receive eribulin and 83.1% (211) to receive TPC. Metastatic tumor site was similar in eribulin and TPC arms, with liver (58.3%; 62.6%), lung (38.8%; 37.4%) and pleural (17.1%; 16.5%) involvement. Patients with visceral disease treated with eribulin demonstrated a significant benefit in OS compared to TPC (HR 0.77, p=0.02). Median OS in mBC pts with visceral disease was 12.45 months (mos) for eribulin-treated pts, with ORR=11.0% and CBR*=21.7% compared to OS=10.12 mos, ORR=5.0%, CBR*=16.6% for TPC-treated patients (*CBR defined as CR+PR+SD>6mos). No significant treatment difference was observed in the non-visceral disease patients however due to the small number of patients with non-visceral disease, no robust statistical conclusions can be made. Conclusions: Treatment with eribulin resulted in significant improvement in overall survival for mBC pts with visceral disease compared to other commonly used chemotherapeutic agents.