bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol consumption: The single most important behavioral risk factor in breast cancer?
Authors: Lautenschlaeger T. , Dedousi-Huebner V. , Chakravarti A. 
Published: February 2017

176 Background: Breast cancer research has identified certain risk factors over the years, which influence a woman's chance of getting the disease. While factors such as personal history of breast abnormalities, age and the occurrence of breast cancer among first-degree relatives have been identified as estimation factors for breast cancer risk, other factors are less conclusive. Increasingly, obesity is being analyzed as a significant risk factor for many cancers and, after tobacco use, may be one of the most modifiable behavioral cancer risk factors. Interestingly when comparing the incidence rate of breast cancer to the obesity rate nationwide many states show a disparity in the two. It may be that other behavioral risk factors are of greater importance. Methods: The US States Mississippi and West Virginia display the highest rates of obesity (over 29.4% of their population display a BMI over 30.0) and the lowest rates in breast cancer incidence nationwide (under 113.9 and 113.5 people per 100.00. residents are diagnosed with cancer each year respectively). We set out to look at various behavioral risk factors to possibly detect an underlying pattern for breast cancer. Using selected metropolitan/micropolitan area risk trend data from the Behavioral Risk Factor Surveillance System from the CDC, we compared median percentages of the following risk factors: health status, exercise, diabetes, flu vaccination, current smoking, binge drinking and obesity. Results: Both states displayed higher percentages in all risk factors compared to the national average except for one in which they were below the national average: binge drinking. Rhode Island and Connecticut, the two states with the highest incidence rates in breast cancer, in turn displayed slightly higher rates of binge drinking compared to the national average. Conclusions: It appears that binge drinking might weigh more than other behavioral factors in terms of risk associated to breast cancer. Future research will need to analyze the interplay and patterns of the various risk factors as well as evaluate the association of mammographic density and alcohol drinking to further investigate the role of alcohol and binge drinking in the development of breast cancer.
May axillary dissection be avoided after micro metastases in sentinel lymph node analyzed by OSNA method?
Authors: Velasco A. , Morales S. , Panades M. J. , Gonzalez S. , Vilardell F. , Canosa C. , Iglesias E. 
Published: February 2017

18 Background: The study of the sentinel node biopsy is a common method to assess axillary involvement before surgical resection. The OSNA assay based on reverse transcriptase loop mediated amplification (RT-LAMP) and quantification of cytokeratin 19 (CK19) mRNA allows a rapid intra-operative detection of the metastases in the sentinel lymph node in breast cancer patients. Pathologists considered micro metastases when the size of the node involvement was between 0.2 and 2 mm and the OSNA method assess micro metastases when the copy number of CK19 is between 250 and 5000. Methods: From a total of 341 patients in which sentinel node had been analyzed, we studied a series of 32 patients whose sentinel nodes had micro metastases assessed by OSNA and who underwent subsequent axillary dissection. Median breast tumour size was 1.6 cm, 10 patients (31%) had less than 1 cm in size and only 6 patients (19%) had >2 cm. 78% of patients shown positive oestrogen receptor and 14 patients (44%) had low Ki67 (<14%). The CK19 mRNA was quantified in all patients (32) resulting in a median value of 540 (210-4800). Results: The median value of the nodes removed by axillary dissection was 14 (9-19). We found tumor invasion in none of them by histopathological conventional study. Conclusions: Since we have found no axillary involvement when the sentinel node have micro metastases analyzed by the OSNA method it seems that quantitative measure of CK19 by OSNA may be a useful procedure in order to avoid axillary dissection, although it would be necessary to perform larger studies to demonstrate this effect.
Predictors and prevalence of germ-line BRCA mutations in high-risk patients among different ethnicities.
Authors: Riaz S. S. , Ahsan S. , Bloom R. E. 
Published: February 2017

190 Background: Germ-line mutations in tumor suppressor genes, BRCA1 and BRCA2, confer high risks of breast and ovarian cancer in affected individuals. Genetic testing for these pathogenic mutations has potentially important health implications for judicious counseling and screening of high risk individuals. Methods: A retrospective analysis was conducted of all the patients seen at our oncology/genetics clinic from 2000 to 2010. A population of over 500 patients was identified, out of whom 310 subjects underwent risk factor assessment. BRCA testing was performed on 231 of these subjects whereas 79 subjects were not tested secondary to lack of insurance/follow up, or patient/physician preference. Various ethnic groups were identified which included 138 Caucasian, 41 African American, 28 Ashkenazi Jewish, 4 Middle Eastern, 2 Asian and 2 Hispanic subjects. The ethnicity of 16 subjects was unknown secondary to lack of documentation. Results: BRCA mutation testing was completed on 231 subjects out of whom 34 were identified as carriers, comprising 31 female and 3 male individuals. 25 subjects carried BRCA1 and 11 subjects carried BRCA2 mutations, whereas 2 subjects carried both mutations simultaneously. In terms of racial prevalence, the population screened was divided into 4 main groups. Using the Maximum Likelihood Ratio Chi-Square Test, a p-value of 0.96 (p=0.9633) was obtained which indicated that the proportion of mutation did not differ for the races among the population screened. Conclusions: The estimated ethnicity prevalence of BRCA mutations was found to be the highest in African American followed by Caucasian and Ashkenazi Jewish subjects in the population screened at our facility. Overall, BRCA mutations are more common in the Jewish population on which most of the research has been focused. Our study is one of the few to indicate the possibility of high prevalence of mutations in the under-studied and less reported high risk kindred, that is, the African Americans. [Table: see text]
In vitro assessment of the inflammatory breast cancer cell line SUM 149: Discovery of two single nucleotide polymorphisms in the RNase L gene.
Authors: Nokes B. T. , Cunliffe H. , Brown A. R. , Sheth G. R. , Stopeck A. , Livingston R. B. , Futscher B. W. , Lang J. E. 
Published: February 2017

196 Background: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer, accounting for 5% of breast cancers diagnosed annually in the United States. Understanding the distinct biology of IBC could help provide novel treatment targets. We sought to evaluate whether or not the IBC cell lines SUM 149 and SUM 190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We also performed proliferation assays; developed dose response curves to assess the treatment effect of interferon-alpha (IFN-a); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated but not definitively associated with IBC,) in the DNA and RNA of SUM 149 cells. Results: According to our allelic discrimination SNP assay, 2/2 IBC cell lines were homozygous for the 462 and 541 variants, whereas 0/10 non-IBC cell lines were homozygous positive for the 462 variant (p = 0.015) and 2/10 non-IBC cell lines contained homozygous alleles for the 541 variant (p = 0.52). We also found a dose and time-dependent decrease in the proliferation of SUM 149 IBC cells treated with IFN-a. In contrast, non-IBC cell lines did not show a dose-response decrease in cell proliferation. Our reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis for the env/LTR and late LTR sequences of the putative HMTV revealed no evidence of the putative viral genome. Conclusions: We discovered 2 SNPs, in the 462 and 541 variants of the RNase L gene, that were homozygously mutated in IBC cell lines but the 462 variant was absent in non-IBC lines. Our discovery of these mutated SNPs present in IBC cell lines suggests a possible genetic risk factor for IBC. In our study, the IBC cell line SUM 149 demonstrated a direct and specific response to treatment with IFN-a, an antiviral agent. We noted no evidence of HMTV infection in that cell line. Further studies of the prevalence and significance of the RNase L 462 and 541 variants in human IBC tissue specimens are warranted to validate our in vitro findings.
The effects of clinical trials on improving breast cancer care at a single institution.
Authors: Dooley W. C. , Parker J. , Bong J. 
Published: February 2017

198 Background: We reported in 2011 at the Society of Surgical Oncology a 19 year retrospective at a single academic institution which identified practice differences between surgical oncologists and general surgeons which were associated with a significant survival advantage. Clinical trial participation was much higher amongst patients treated by a surgical oncologist. Methods: This is an IRB approved, retrospective review of all breast cancer patients receiving primary treatment at a single institution from 1/1/2001 to 12/31/2008. Details of pathology, surgical therapy, chemotherapy, hormonal therapy and radiation therapy were compared between patients participating in clinical trials and those not participating. The specific trials were segregated as to type (tissue banking, therapeutic, prevention, etc.) to understand differential effects if any between type of trial participation. Results: During the time period, there were 1220 patients who received primary breast cancer treatment at this institution. The mean age was 55.6 and mean follow-up >40 months. Stage distribution was stage 0 - 16.8%, Stage 1 - 26.6%, Stage 2 - 33.1%, Stage 3 - 15.9%, and Stage 4 - 6.1%. Patients participating in any clinical trial numbered 468 and 752 participated in no clinical trials. Overall survival (clinical trial 98.8% vs. not in clinical trial 75.7%; p<0.0001). Overall the use of breast conservation was more likely in clinical trial participants (54.3% vs. 44.4%; p<0.0001). The completion of chemotherapy was more likely in clinical trial participants (52.4% vs. 49.5%; p=0.02).The successful completion of systemic therapies (chemo and hormonal) was more likely also (71.4% vs. 64.0%; p=0.009). The type of trial (tissue banking vs. therapeutic) had no effect on improved outcomes. Overall the best predictor of better outcomes was to be treated by a high volume clinical trial enrolling physician. Conclusions: High volume clinical trial enrollment is associated with the best overall treatment outcomes in breast cancer whether trials are directly related to therapeutic changes or not. Each individual in the breast center treating team can have dramatic effect on outcomes by improving their clinical trial enrollment and participation.
Prediction of late recurrences by breast cancer index in the NCIC CTG MA.17 cohort.
Authors: Sgroi D. , Carney E. , Richardson E. , Steffel L. , Binns S. N. , Finkelstein D. M. , Shepherd L. E. , Kesty N. C. , Schnabel C. , Erlander M. G. , Ingle J. N. , Porter P. , Paik S. , Muss H. B. , Pritchard K. I. , Tu D. , Goss P. E. 
Published: February 2017

2 Background: The MA.17 trial demonstrated that extended adjuvant endocrine therapy with letrozole after 5-y of tamoxifen markedly reduced the risk of recurrence in women with ER+ early stage breast cancer. This trial provides an opportunity to assess the ability of biomarkers to predict late recurrences in ER+ breast cancer. The Breast Cancer Index (BCI), a continuous risk index based on the combination of HOXB13:IL17BR (H:I) and the molecular grade index (MGI), estimates the individual risk of recurrence in ER+ breast cancer patients. In this study, the prognostic utility of BCI to predict late recurrences was examined. Methods: FFPE tumor blocks were collected from patients who experienced a breast cancer recurrence up to unblinding of MA.17. Controls were matched 2:1 for age, tumor size, nodal status and prior chemotherapy, and were disease free for longer than cases. All cases were reviewed for standard histopathology and evaluated using the real-time RT-PCR BCI assay. Results: Patient characteristics for the case-control study were similar to that from the overall study. Characteristics for cases (N=83) and controls (N=166) were not significantly different except for treatment. A higher percentage of controls compared to cases tended to be categorized as low risk by BCI (58% vs 43%), while a lower percentage of controls than cases tended to be categorized as high risk by BCI (34% vs 24%). In univariate analysis, treatment, BCI, H:I and HOXB13, but not tumor grade or MGI, were significant predictors of late recurrence. After adjusting for standard variables (age, tumor grade and treatment), BCI (OR 2.37; P=0.03), H:I (OR 2.55; P=0.04) and HOXB13 (OR 1.35; P=0.02) remained significant predictors of recurrence. HOXB13 expression at diagnosis predicted patient benefit from extended endocrine therapy with letrozole. Conclusions: In this case-controlled study, the data demonstrate that BCI is a significant predictor of late recurrences in ER+ patients following 5-y of tamoxifen. The prognostic performance of BCI to predict late recurrences was largely dependent on HOXB13 expression. The integration of H:I and MGI within BCI provides prognostic utility for both early and late recurrences.
Quality assurance review center: Role in multi-institutional breast cancer trials.
Authors: Moni J. , Le-Petross H. T. , Boughey J. C. , Laurie F. , Hanusik R. , Howley S. , Logan D. G. , Bishop-Jodoin M. , Simmons R. M. , Ellis M. J. , Hunt K. , Cicchetti M. G. , Sioshansi S. , Quinlan R. M. , Whalen G. F. , Fitzgerald T. J. 
Published: February 2017

205 Background: Central review is an important trial management and validation tool. Multisite trials require data systems to accommodate diverse image acquisition and review. Breast cancer is challenging as its imaging objects are not always easily shared across departments. Quality Assurance Review Center (QARC) has a diverse portfolio of facile data acquisition and powerful informatics support that meets these needs. We report on the role of QARC in three of the current breast cancer trials from the American College of Surgeons Oncology Group. Methods: QARC data management system includes secure network infrastructure and a validated relational operating database (MAX). QARC has data acquisition/imaging re-distribution expertise for real time response reviews, response measuring tools and corresponding data archive for secondary reviews. MAX includes query ability; records link to digital information. QARC underwent systematic information systems validation process for 21 CFR Part 11. DICOM/non-DICOM files are stored in the QARC PACS. On-site/remote reviewers use MAX to retrieve, view, annotate and save images. Data extracted is securely sent to partner statistical centers. Results: In Z1031, a neoadjuvant endocrine therapy trial, all of the mammographic exams are archived at QARC. For Z1071, a sentinel lymph node trial, pre- and post-treatment ultrasound (US) images of 321 patients were remotely reviewed. For Z1072, the cryoablation US, pre and post-cryoablation MRI for 40 of 47 cases were remotely archived, retrieved and transferred to investigator workstation for post-processing and review. The other 7 patients did not have evaluable imaging studies. In all three trials, the costs of shipping hardcopies of exams and travel to QARC for central review functions were eliminated. Conclusions: QARC data management systems provide diverse informatics supports for multi-institutional trials, ranging from archives of images, provide remote access and download of data, and central review. The vibrant informatics supports meet the growing needs of clinical trials. Future directions include radiation field review for breast cancer trials and the incorporation of pathology microarray analysis as DICOM objects.
Multidisciplinary care of the breast cancer survivor: An innovative approach.
Authors: Morrow P. K. H. , Bevers T. B. , Zandstra F. , Russell L. 
Published: February 2017

206 Background: The Institute of Medicine recognizes cancer survivorship as an integral part of cancer care and advocates for appropriate survivorship care. We will describe the development of a Multidisciplinary Breast Survivorship Clinic (MBSC) and the metrics used to assess the program’s progress. Methods: To ensure effective integration of a MBSC into a major comprehensive cancer center, clinical leaders (in both the institution and breast leadership group) were approached and engaged in facilitating smooth transitioning of patients from the breast clinic to the survivorship domain. Eligibility criteria included: time of diagnosis ≤ 5 years and no evidence of active breast malignancy. After establishing these criteria, a multidisciplinary team (including endocrinologists, family physicians, medical oncologists, nurses, and research librarians) conducted an extensive literature review of evidence-based disease surveillance, risk reduction, screening for second cancers, and late effects of treatment modalities. These data became the basis of practice algorithms for invasive breast cancer, noninvasive breast cancer, and bone health. Treatment pathways included 4 domains of care: surveillance of the primary malignancy, risk reduction, cancer screening, and monitoring for late effects. The Passport Plan for Health (Passport) evolved from these domains. Results: Metrics used to assess the MBSC’s progress included number of survivors seen the clinic and number receiving Passports. Each patient is seen on the day of her mammogram (if clinically appropriate) and given a Passport on the initial visit, as well as subsequent visits. Between 9/1/2009-5/16/2011, 3594 patients participated in the Breast Survivorship Clinic. Of the 3584 patients seen in the survivorship clinic, 3435 patients received a completed Passport. Conclusions: The Passport strengths are to: facilitate communication with primary care physicians, communicate the care needs of the patient and designate the health care provider for their evaluation. Models of care such as the Multidisciplinary Breast Survivorship Clinic provide a rich environment to facilitate survivorship research aimed at assessing the optimal approach to the breast cancer survivor.
Improvement in the quality of care for patients with locally advanced breast cancer through implementation of an integrated electronic care pathway.
Authors: Hogeveen S. , Han D. , George R. L. , Sweet-Goldstein M. , Dinniwell R. E. , Muradali D. , Brezden C. B. , Haq R. , Simmons C. E. 
Published: February 2017

207 Background: Locally advanced breast cancer (LABC) refers to the most advanced stage of non-metastatic tumours with an incidence of approximately 10% in newly diagnosed breast cancers. Currently, for optimal care, patients with LABC require a multidisciplinary approach including coordinated planning with medical, surgical and radiation oncologists. We created an interactive electronic care pathway and self populating quality assurance database at St. Michael’s Hospital (SMH) to facilitate multidisciplinary teams to track LABC patient histories and patient treatments in order to coordinate therapy effectively and expedite care (LABC E-PATH). Methods: This is an observational before-and-after cohort study of patients with LABC with a retrospective review pre-implementation and prospective collection of clinical data post-implementation. The completeness of workup and the timeliness of treatment pre- and post-implementation of the LABC E-PATH in May 2010 were assessed. Results: With the implementation of the LABC E-PATH in May 2010 at SMH, the delay between the identification of the patient as LABC and their referral to a medical oncologist for treatment for their LABC decreased from a median of 9 days pre-implementation, (range 0-780 days) to 1 day post-implementation, (range 0-52 days). The time between referral to medical oncologist and the start of their chemotherapy treatment decreased from a median of 12 days to 9 days (pre-implementation: range = 4 to 494, post-implementation: range = 0 to 39). All pre-treatment staging was completed faster post-implementation of the LABC e-path than pre-implementation, expediting time to initiation of chemotherapy. The number of referrals for LABC to the SMH program increased from < 1 patient per month to 5 patients per month post-implementation. Conclusions: The LABC E-PATH at SMH has achieved its goal of expediting care for this patient population. It has also ensured timely and appropriate resource allocation. This unique system may also be applied to other disease sites where coordination of a multi-disciplinary team is critical for appropriate patient management.
Influence of breast cancer CME on provider knowledge and competence.
Authors: Stacy T. B. , Heintz A. A. , Dopson K. , McLane K. , Haas M. E. 
Published: February 2017

214 Background: Due to the volume and pace of scientific advances within oncology, the timely dissemination of clinical trial results and discussion regarding the appropriate incorporation into therapeutic decision making is necessary to provide the highest quality patient care. Increasing awareness in the breast cancer community on similarities and differences amongst practice management strategies helps to identify practice patterns and benchmark individual knowledge and competence against one’s professional peers. Methods: During 2010 and 2011, educational outcomes assessments were gathered during 83 independent continuing medical education (CME) activities held within community and academic institutions across the USA. Participants were asked a series of case-based questions via an audience response system to assess baseline knowledge, competence, and identify practice patterns. Assessments were repeated post a 1-hour CME certified activity, with an additional 6-week electronic follow-up. Barriers to implementing the information learned were also captured. Educational gaps were identified through documentation and comparison of current best practices versus actual participant responses. Results: To date, a total of 1,515 healthcare providers have participated in the initiative. Number of years in practice ranged from <10 to >30. The number of breast cancer patients seen per month ranged from ≤10 to >40. Provider competency in applying recent literature to the patient care setting was both assessed and measured. Results of neoadjuvant data knowledge, adjuvant therapy selection, relapsed HER2+ disease treatment strategies, and competence in discussing efficacy and safety data from recent clinical trials will be presented. Participants reported a number of barriers to applying data learned at the activities into clinical practice. Responses included lack of reimbursement, treatment side effects, newness of treatment data, and perceived efficacy. Conclusions: The results suggest the education of providers on the most currently available clinical trial results and expert discussion of how to optimize translation of this information into patient care increases breast cancer provider knowledge and competence.