Dolly Han

Mammographic microcalcifications and breast cancer tumorigenesis: a radiologic-pathologic analysis

BackgroundMicrocalcifications (MCs) are tiny deposits of calcium in breast soft tissue. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their significance in breast tumorigenesis is controversial. This study had two objectives: (1) to find associations between mammographic MCs and tumor pathology, and (2) to compare the diagnostic value of mammograms and breast biopsies in identifying malignant MCs.MethodsA retrospective chart review was performed for 937 women treated for breast cancer during 2000–2012 at St. Michael’s Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 over-expression and presence of MCs were collected. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All p-values less than 0.05 were considered statistically significant.ResultsA total of 937 patient charts were included. About 38.3% of the patients presented with mammographic MCs on routine mammographic screening. Patients were more likely to have MCs if they were HER-2 positive (52.9%; p < 0.001). There was a significant association between MCs and peri-menopausal status with a mean age of 50 (64%; p = 0.012). Patients with invasive ductal carcinomas (40.9%; p = 0.001) were more likely to present with MCs than were patients with other tumor histologies. Patients with a heterogeneous breast density (p = 0.031) and multifocal breast disease (p = 0.044) were more likely to have MCs on mammograms. There was a positive correlation between MCs and tumor grade (p = 0.057), with grade III tumors presenting with the most MCs (41.3%). A total of 52.2% of MCs were missed on mammograms which were visible on pathology (p < 0.001).ConclusionThis is the largest study suggesting the appearance of MCs on mammograms is strongly associated with HER-2 over-expression, invasive ductal carcinomas, peri-menopausal status, heterogeneous breast density and multifocal disease.

Early economic evaluation of emerging health technologies: protocol of a systematic review

BackgroundThe concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice.Methods/designThis protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to identify, measure, and value the likely effectiveness and the costs and consequences of the new technology, handling of uncertainty), and whether the study results adequately address the main study question or objective. Data will be summarized overall and stratified by publication status.DiscussionThis study is timely to inform early economic evaluation practice, given the international trend in early health technology assessment initiatives.

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of

Comparison of international breast cancer guidelines: are we globally consistent? cancer guideline AGREEment.

78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase guideline adherence.

Multiple Dimensions of Value: Evaluative Frameworks for New Cancer Therapies

BACKGROUND Evidence-based guidelines are used in health care systems throughout the world to aid in treatment decisions and to ensure quality and consistency in patient care. In breast oncology, guidelines for care are published by several internationally recognized organizations, including those from the United States, Canada, and the United Kingdom. The present study compared clinical breast cancer guidelines from the American Society of Clinical Oncology (ASCO, United States), Cancer Care Ontario (CCO, Canada), and the National Institute for Health and Clinical Excellence (NICE, United Kingdom) to determine the quality and consistency of content across international organizations. METHODS We searched for breast cancer guidelines published by ASCO, CCO, and NICE. Guidelines on the same theme were identified across organizations and appraised by 4 independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Content of each guideline was also scored for consistency in overall recommendations across organizations and for consistency in cited evidence. RESULTS The quality of breast cancer guidelines produced by the targeted organizations was consistently good in the areas of Scope and Purpose, Rigor of Development, and Clarity and Presentation, but variable in the domains of Stakeholder Involvement, Applicability, and Editorial Independence. The content of the guidelines varied slightly in the strength of their recommendations. CONCLUSIONS Our review demonstrated consistency in quality and content for breast cancer practice guidelines published by various organizations. Future guidelines developed by these organizations should focus on how to implement and measure uptake of a guideline.

A Canadian national expert consensus on neoadjuvant therapy for breast cancer: linking practice to evidence and beyond

TO THE EDITOR: The increasing burden of costs associated with novel cancer therapies has become untenable. In the United States, the annual cost of a new cancer therapy routinely exceeds

Identifying knowledge-translation opportunities in the treatment of locally advanced breast cancer.

100,000; such costs may prevent patients from receiving effective options or only enable access under risk of significant financial duress or bankruptcy. In this context, we applaud the recent development of the ASCO Value Framework, a tool that enables physicians and patients to discuss the relative value of a new cancer therapy compared with the standard of care. The framework assesses benefit and toxicity of a cancer therapy through a net health benefit score while highlighting the direct drug costs borne by patients. A core tenet in ASCO’s process was to ensure that the framework development was transparent and malleable. Some criticisms already have targeted the arbitrariness of net health benefit scoring and limited perspective on costs as well as the inability of the framework to evaluate the methodological strength of evidence, consider noncomparative studies despite the increasing propensity for regulatory drug approvals based on earlier-phase trials, and evaluate scenarios in which multiple comparators represent current standards or for which nontrial (real-world) data are available. Over time, these limitations in the initial process may be addressed or proven of minimal consequence; certainly, we now have a much-needed starting point for a dialogue with patients on relative clinical benefit and costs. We highlight that additional dimensions may also warrant consideration to create the most fulsome assessment of value. In particular, such factors as patient preferences, burden of illness, feasibility of adoption, and formal cost-effectiveness analysis (CEA) may broaden the perspective of value from the individual level to society at large. Since 2007, the provinces and territories of Canada (with the exception of Quebec) have participated in the pan-Canadian Oncology Drug Review (pCODR). pCODR provides evidencebased cancer drug funding recommendations and evolved from iterative processes for formal evaluation of cancer therapies at a national level that have spanned more than a decade. The Canadian experience suggests that although clinical and economic evidence are fundamental building blocks for evaluation, additional factors often come into play when funding decisions are implemented. As such, pCODR follows an established deliberative framework (Table 1) in making recommendations by systematically assessing clinical and economic evidence in addition to patient perspectives and the feasibility of drug adoptionwithin the provincial context and budget. The framework aspires to ensure that no single element overrides another and that no single threshold must be met for any element in the review. Can these additional elements enhance our understanding of value beyond the traditional pillars of benefit and drug costs already considered by ASCO? In its consideration of benefit, pCODR expands its scope beyond efficacy and safety to consider quality of life, burden of illness on society, and availability of

Abstract P2-01-05: Mammographic microcalcifications and breast cancer tumorigenesis: A radiologic-pathologic analysis

BACKGROUND Use of the neoadjuvant approach to treat breast cancer patients has increased since the early 2000s, but the overall pathway of care for such patients can be highly variable. The aim of our project was to establish a multidisciplinary consensus among clinicians with expertise in neoadjuvant therapy (nat) for breast cancer and to determine if that consensus reflects published methods used in randomized controlled trials (rcts) in this area. METHODS A modified Delphi protocol, which used iterative surveys administered to 85 experts across Canada, was established to obtain expert consensus concerning all aspects of the care pathway for patients undergoing nat for breast cancer. All rcts published between January 1, 1967, and December 1, 2012, were systematically reviewed. Data extracted from the rcts were analyzed to determine if the methods used matched the expert consensus for specific areas of nat management. A scoring system determined the strength of the agreement between the literature and the expert consensus. RESULTS Consensus was achieved for all areas of the pathway of care for patients undergoing nat for breast cancer, with the exception of the role of magnetic resonance imaging in the pre-treatment or preoperative setting. The levels of agreement between the consensus statements and the published rcts varied, primarily because specific aspects of the pathway of care were not well described in the reviewed literature. CONCLUSIONS A true consensus of expert opinion concerning the pathway of care appropriate for patients receiving nat for breast cancer has been achieved. A review of the literature illuminated gaps in the evidence about some elements of nat management. Where evidence is available, agreement with expert opinion is strong overall. Our study is unique in its approach to establishing consensus among medical experts in this field and has established a pathway of care that can be applied in practice for patients receiving nat.

P5-08-04: Mammographic Microcalcifications and Breast Cancer Tumorigenesis: A Radiologic-Pathologic Analysis.

47 Background: Guidelines are usually developed using systematic literature reviews. Expert opinion plays a key role but can be difficult to incorporate. The objective of this study was to develop a national consensus of expert opinion on the management of Locally Advanced Breast Cancer (LABC) and subsequently identify gaps in knowledge translation in current practice. METHODS 361 Canadian oncologists were subdivided into LABC experts (n = 83) and non-experts (n = 278). Experts were surveyed with a modified Delphi protocol to establish consensus. A systematic literature review was performed and compared to expert opinion. Non-experts were then surveyed with a 29-item questionnaire to determine current practice patterns. Z test was used to assess discordance. RESULTS Response rate for the expert survey was 61% (51/83). Consensus was achieved in all key aspects of care and was concordant to published literature in areas of: clinical assessment with caliper at each cycle, option of lumpectomy if good clinical response, radiotherapy to loco-regional lymph nodes, and no further adjuvant chemotherapy outside of clinical trial if residual disease found at time of surgery. Response rate for the non-expert survey was 50% (140/278). Areas of discordance are highlighted below. CONCLUSIONS A national practice consensus guideline reflective of current evidence and expert opinion has been developed on the management of LABC. Differences in expert opinion and current practice have been identified as targets for knowledge translation interventions (KTIs) that may improve quality of care and resource utilization. Further exploration of KTIs to address identified gaps is warranted. [Table: see text].

P1-11-13: Improvement in the Quality of Care for Patients with Locally Advanced Breast Cancer through Implementation of an Integrated Electronic Care Pathway.

Background: Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. They serve as key diagnostic radiological features for localization of malignancy. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their role in breast cancer tumorigenesis is currently unknown. The purpose of this study was to investigate the relationship between mammographic MCs and breast cancer pathology. Methods: A retrospective chart review was performed for 1015 women treated for breast cancer between 2000-2012 at St. Michael9s Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 overexpression and presence of MCs were collected for breast cancer patients. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All tests were two-sided and p-values less than 0.05 were considered statistically significant. Results: A total of 1015 patient charts were included; 78 (7.7%) patients had metastatic carcinoma and were excluded from analysis. About 38.3% (287/1015) of the patients presented with mammographic MCs. Patients were more likely to have MCs if they were HER-2 positive (52.9%) as opposed to being HER-2 negative (33.8%) (p Conclusion: This is the largest study analyzing data over a 12 year period, suggesting that the appearance of MCs on mammograms is strongly associated with HER-2 overexpression, invasive ductal carcinoma, heterogeneous breast density and multifocal breast cancers. Since HER-2 is implicated in mediating aggressive tumor growth and metastasis, future studies should investigate the molecular pathways connecting HER-2 overexpression and MC development. This would help better understand the role of MCs in breast cancer tumorigenesis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-01-05.