Zur Entscheidungshilfe in der Therapiefindung des Mammakarzinoms haben sich bezüglich der Indikation zur Chemotherapie neben den klinischen und histopathologischen Kriterien in den letzten Jahren vorrangig Multigentests etabliert. In der vorliegenden Arbeit wurden Zusammenhänge zwischen dem Oncotyp DX® und 18 immunhistochemischen Markern aus der Tumorbiologie für 78 Fälle hormonrezeptorpositiver, Her2/neu negativer Mammafrühkarzinome mit niedrigem Lymphknotenstatus untersucht. Es erfolgten immunhistochemische Färbungen an Microtissue-Arrays der Tumorproben. Für die Marker AMACR, Cyclin D1, p53, MDM2 und PDL1 ergab sich eine klare statistisch signifikante Korrelation zum Recurrence-Score®des Oncotyp DX® und mit Einschränkungen auch für CDK4. Die Marker p27, Bcl2 und Glut 1 erreichten ein etwas niedrigeres Signifikanzniveau in der statistischen Analyse. Der immunhistochemische Routinemarker Ki67% zeigte eine hochsignifikante Korrelation mit dem Recurrence-Score®. Hierdurch ergeben sich neue Perspektiven zur Risikostratifizierung des Mammakarzinoms, wie beispielsweise die konsekutive Entwicklung eines immunhistochemischen Scores mit prädiktivem Wert für den Recurrence-Score® mit klinischer Anwendung als Prätest oder als eigenständiges Stratifizierungstool bei Brustkrebs. / In addition to clinical and histopathological criteria, multigene tests have become established in recent years as a decision-making aid in the treatment of breast carcinoma.with regard to the indication for chemotherapy. In the present study, correlations between Oncotype DX® and 18 immunohistochemical markers from tumour biology were investigated for 78 cases of hormone receptor-positive, Her2/neu-negative early breast carcinoma with low lymph node status. IImmunohistochemical staining was carried out on microtissue arrays of the tumor samples.There was a clear, statistically significant correlation for AMACR, Cyclin D1, p53, MDM2 and PDL1, to the Recurrence Score® of the Oncotype DX® and with limitations, also for the marker CDK4. p27, Bcl2 and Glut 1 reached a slightly lower significance level in the statistical analysis. Ki67%, a routine immunohistochemical marker, showed a highly significant correlation with the Recurrence-Score®. This opens up new perspectives for risk stratification of breast cancer, such as the consecutive development of an immunohistochemical score with predictive value for the Recurrence-Score® meant for clinical application as a pre-test or as an independent stratification tool for breast cancer.

Background: New genomic tests are being developed to predict an individual’s risk of cancer recurrence by analyzing the expression of multiple genes. However, it is unclear how to report the test results so that they would be most useful to clinicians. A mail-out questionnaire has the potential to help a) describe physicians’ attitudes towards the clinical use of new genomic tests, b) determine what information physicians prefer to have included in the test reports, and c) explore how physicians think the test results would impact their treatment recommendations. Objectives: To design such a questionnaire that could be used in the eventual large-scale survey, and to ensure that the questionnaire a) is comprehensible, b) has face validity, c) appears interesting to, and d) does not place undue response burden on, the target population. Methods: The first draft, based on a specific genomic test for breast cancer recurrence (Oncotype DX) and on two case scenarios, was created. Cognitive interviews with practicing oncologists were conducted to identify problems in the questionnaire. The evaluation involved face-to-face interviews with Kingston oncologists who treat breast cancer, followed by telephone interviews with medical oncologists who treat breast cancer in other places in Ontario. Three-to-four oncologists were included in each round of interviewing after which the questionnaire was revised based on that round’s recommendations. Additional rounds of interviews were conducted until no new problems/issues were raised in one entire round. Results: A medium-length questionnaire was drafted. Four rounds of interviews were conducted with no new problems/issues being raised in the fourth round. Most of the problems identified in the questionnaire related to comprehensibility, followed by logical issues which detected fundamental problems in the questionnaire design. There was no evidence of fatigue or disinterest in participants and they deemed the response burden reasonable. Conclusion: The results suggest that the proposed questionnaire is comprehensible and has face validity. Additionally, it appears to be an interesting questionnaire to, and would not place undue burden on, the target population. Thus, the questionnaire is now ready for the field administration. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2009-05-05 17:23:10.551

The decision for adjuvant therapy in women with early stage breast cancer (ESBC) has historically been guided by the presence or absence of specific biological markers (hormone and HER2 receptors), age, and extent of nodal involvement. Oncotype DX® is a validated assay that quantifies protein expression that can predict the risk of cancer recurrence. This study evaluates if the use of Oncotype DX® impacts chemotherapy prescribing in ESBC. This retrospective, cohort study identified patients with ESBC from a large commercially insured population from January 2007 through June 2009. Patients were identified as having ESBC by utilizing procedure and diagnosis codes to indicate that a sentinel lymph node biopsy had been performed. Hormone receptor status was verified by patients receiving at least one month of hormonal therapy including: tamoxifen, anastrozole, letrozole, or exemestane. Exclusion criteria will include patients less than 18 years of age, procedure codes indicating axillary lymph node dissection, or charges for trastuzumab. The administration of Oncotype DX® was not found to significantly affect a physician’s decision to prescribe chemotherapy. However, there were significant regional differences in Oncotype DX® utilization by region. Future studies should be conducted at a population level to determine the effects of Oncotype DX®.