Automated image analysis for high-throughput quantitative detection of ER and PR expression levels in large-scale clinical studies: the TEAM Trial Experience.

AIMS: Routine immunohistochemistry is regarded as a semiquantitative method for the evaluation of in situ protein expression. Analysis of tissue biomarkers in large clinical trials is central to the development of novel targeted approaches to therapy, requires the analysis of tens of thousands of data points, and frequently makes use of high-throughput analysis of tissue microarrays (TMAs). The aim of this study was to investigate the potential of image analysis for accurate and reproducible quantitative evaluation of biomarkers. METHODS AND RESULTS: We showed, in 397 cases of breast cancer from the Phase III TEAM clinical trial, excellent correlations between semiautomated image analysis of TMAs and manual scoring of oestrogen receptor (ER) and progesterone receptor (PR) levels (interclass correlation coefficients 0.93 and 0.96 respectively). Two or more TMA cores were excellently correlated with manual scores, and using more than three cores increased the number of cases available for analysis to >92%. TMAs are confirmed as representative of whole sections for immunohistochemical analysis of the tissue biomarkers ER and PR. CONCLUSIONS: Semiautomated image analysis is appropriate for the analysis of tissue biomarkers within large clinical trials. These data provide support for the use of TMAs and image analysis in translational research.

International Consensus on the Clinical Management of Inflammatory Breast Cancer from the Morgan Welch Inflammatory Breast Cancer Research Program 10th Anniversary Conference.

National and international experts in inflammatory breast cancer (IBC) from high-volume centers treating IBC recently convened at the 10th Anniversary Conference of the Morgan Welch Inflammatory Breast Cancer Research Program at The University of Texas MD Anderson Cancer Center in Houston Texas. A consensus on the clinical management of patients with IBC was discussed, summarized, and subsequently reviewed. All participants at the conference (patients, advocates, researchers, trainees, and clinicians) were queried using the MDRing electronic survey on key management issues. A summary of the expert consensus and participant voting is presented. Bilateral breast and nodal evaluation, breast magnetic resonance imaging, positron emission tomography/computed tomography, and medical photographs were endorsed as optimal. Neoadjuvant systemic therapy, modified radical mastectomy and level I and II ipsilateral axillary node dissection, post-mastectomy radiotherapy, adjuvant targeted therapy and hormonal therapy as indicated, and delayed reconstruction were agreed-upon fundamental premises of standard non-protocol-based treatment for IBC. Consideration for local-regional therapy in de novo stage IV IBC was endorsed to provide local control whenever feasible. Variation across centers and special circumstances were discussed.

The MAGIC survey in hormone receptor positive (HR+), HER2-negative (HER2-) breast cancer: When might multigene assays be of value?

BACKGROUND: A modest proportion of patients with early stage hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer benefit from adjuvant chemotherapy. Traditionally, treatment recommendations are based on clinical/pathologic criteria that are not predictive of chemotherapy benefit. Multigene assays provide prognostic and predictive information that can help to make more informed treatment decisions. The MAGIC survey evaluated international differences in treatment recommendations, how traditional parameters are used for making treatment choices, and for which patients treating physicians feel most uncertain about their decisions. METHODS: The MAGIC survey captured respondents' demographics, practice patterns, relevance of traditional parameters for treatment decisions, and use of or interest in using multigene assays. Using this information, a predictive model was created to simulate treatment recommendations for 672 patient profiles. RESULTS: The survey was completed by 911 respondents (879 clinicians, 32 pathologists) from 52 countries. Chemo-endocrine therapy was recommended more often than endocrine therapy alone, but there was substantial heterogeneity in treatment recommendations in 52% of the patient profiles; approximately every fourth physician provided a different treatment recommendation. The majority of physicians indicated they wanted to use multigene assays clinically. Lack of reimbursement/availability were the main reasons for non-usage. CONCLUSIONS: The survey reveals substantial heterogeneity in treatment recommendations. Physicians have uncertainty in treatment recommendations in a high proportion of patients with intermediate risk features using traditional parameters. In HR+, HER2- patients with early disease the findings highlight the need for additional markers that are both prognostic and predictive of chemotherapy benefit that may support more-informed treatment decisions.