BACKGROUND Breast conservative surgery (CS) with radiotherapy (RT) is the most commonly used treatment for early‐stage breast carcinoma. However, there is controversy regarding the importance of the pathologic margin status on the risk of ipsilateral breast tumor recurrence (IBTR). The current study evaluated the effect of the pathologic margin status on IBTR rates in a cohort of women with lymph node‐negative breast carcinoma treated with CS and RT. METHODS Between August 1980 and December 1994, 452 women with pathologically lymph node‐negative breast carcinoma were treated with CS and RT at Westmead Hospital (Westmead, Australia). Central pathology review was performed for all women. The final margins were negative for 352 women (77.9%), positive (invasive and/or in situ) for 42 women (9.3%), and indeterminate for 58 women (12.8%). Information regarding an extensive intraductal component (EIC), lymphovascular invasion, pathologic tumor size, histologic grade, and nuclear grade was available for most women. After macroscopic total excision of the tumor, all women received whole‐breast irradiation (usually 45–50.4 grays [Gy]) and the majority of women also received a local tumor bed boost (range, 8–30 Gy). RESULTS After a median follow‐up of 80 months, 34 women (7.5%) developed an IBTR. The crude 5‐year rates of IBTR for women with negative margins, positive margins, and indeterminate margins were 3.1%, 11.9%, and 6.9%, respectively. For women with negative margins, the 5‐year and 10‐year actuarial rates of freedom from IBTR were 96% and 92%, respectively, compared with 88% and 75%, respectively, for women with positive margins (P = 0.003). Univariate analysis demonstrated that the only factors associated with a significantly higher risk of IBTR were age at diagnosis (P < 0.050) and margin status (P = 0.005). Multivariate analysis showed that both age and margin status were independent predictors of IBTR. None of 24 patients with an EIC and negative margins were found to have developed an IBTR. CONCLUSIONS The results of the current study were comparable to other published reports and supported the association of higher IBTR rates with positive or indeterminate margins compared with negative, pathologic margins. Furthermore, young age (age < 35 years at diagnosis) was associated with the highest risk of IBTR regardless of margin status. Cancer 2004. © 2004 American Cancer Society.

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Purpose: Increased incidence of ductal carcinoma in situ (DCIS) associated with mammographic screening for breast cancer has emphasized the challenges of managing this condition.The aim of this study was to identify informative clinical indicators of DCIS biology by molecular profiling. Experimental Design: Areas of in situ carcinoma, atypical ductal hyperplasia, and benign epithelium were microdissected from 46 invasive breast cancers. Oligonucleotide probes showing differential expression between DCIS associated with grade 1 and 3 invasive cancer were identified by microarray-based gene expression profiling. Expression at these probes was used to define a ''molecular grade'' subcategorization of all samples. The genomic basis of molecular grade was examined by array-based comparative genomic hybridization. Clinical course was examined in a cohort of 134 patients with DCIS treated by surgery alone. Results: DCIS samples were designated as low or high molecular grade based on expression at 173 probes. The low molecular grade subgroup included low (n = 10) and intermediate (n = 11) nuclear grade DCIS as well as all samples of atypical ductal hyperplasia (n = 4) and benign epithelium (n = 7). The high molecular grade subgroup included DCIS of intermediate (n = 7) and high (n = 19) nuclear grade. The character and degree of genomic aberration were distinct between molecular grade subgroups. A classification tree model including nuclear grade and Ki67 score accurately predicted molecular grade for 95.7% of samples. In an independent cohort, this showed a pattern of rapid disease recurrence for high molecular grade DCIS. Conclusions: Molecular profiling indicates a binary grading scheme for DCIS. This practical approach has potential to improve clinical evaluation of DCIS.

Background: Diagnostic cytopathology is an essential part of clinical decision-making. However, due to a combination of factors including curriculum reform and shortage of pathologists to teach introductory cytopathology, this area of pathology receives little or no formal attention in most medical school curricula. We have previously described the successful use of efficient and effective digital learning resources, including whole slide images (WSI) and virtual microscopy adaptive tutorials (VMATs), to teach cytopathology to pathology specialist trainees -a group that had prior exposure to cytopathology in their day to day practice. Consequently, in the current study we attempted to demonstrate the efficiency and efficacy of this eLearning resource in a cohort of senior medical students that was completely naïve to the subject matter (cytopathology). Methods: We evaluated both the quantitative and qualitative impact of these digital educational materials for learning cytopathology compared with existing resources (e-textbooks and online atlases). The senior medical students were recruited from The University of New South Wales Australia for a randomized cross-over trial. Online assessments, administered after each arm of the trial, contained questions which related directly to a whole slide image. Two categories of questions in the assessments (focusing on either diagnosis or identification of cellular features) were utilized to determine efficacy. User experience and perceptions of efficiency were evaluated using online questionnaires containing Likert scale items and open-ended questions.

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