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D o e s T i m i n g o f A d j u v a n t C h e m o t h e r a p y f o r E a r l y B r e a s t C a n c e r I n fl u e n c e S u r v i v a l ?By C. Shannon, S. Ashley, and I.E. SmithPurpose: Theoretically, patients with early breast cancer might benefit from starting adjuvant chemotherapy soon after surgery, and this would have important clinical implications. We have addressed this question from a large, single-center database in which the majority of patients received anthracyclines.Patients and Methods: A total of 1,161 patients from a prospectively maintained database treated with adjuvant chemotherapy for early breast cancer at the Royal Marsden Hospital (London, United Kingdom), including 686 (59%) receiving anthracyclines, were retrospectively analyzed. The disease-free survival (DFS) and overall survival (OS) of the 368 patients starting chemotherapy within 21 days of surgery (group A) were compared with those of the 793 patients commencing chemotherapy > 21 days after surgery (group B). Median follow-up time was 39 months (range, 12 to 147 months).Results: No significant difference in 5-year DFS was found between the two groups overall (70% for group A v 72% for group B; P ‫؍‬ .4) or in any subgroup. Likewise, there was no difference in 5-year OS (82% for group A v 84% for group B; P ‫؍‬ .2) or when the interval to the start of chemotherapy was considered as a continuous variable (P ‫؍‬ .4). Conclusion:We have been unable to identify any significant survival benefit from starting adjuvant chemotherapy early after surgery, either overall or in any subset of patients.

Subtypes of renal tumors have different genetic backgrounds, prognoses, and responses to surgical and medical treatment, and their differential diagnosis is a frequent challenge for pathologists. New biomarkers can help improve the diagnosis and hence the management of renal cancer patients. We extracted RNA from 71 formalin-fixed paraffin-embedded (FFPE) renal tumor samples and measured expression of more than 900 microRNAs using custom microarrays. Clustering revealed similarity in microRNA expression between oncocytoma and chromophobe subtypes as well as between conventional (clear-cell) and papillary tumors. By basing a classification algorithm on this structure, we followed inherent biological correlations and could achieve accurate classification using few microRNAs markers. We defined a two-step decision-tree classifier that uses expression levels of six microRNAs: the first step uses expression levels of hsa-miR-210 and hsa-miR-221 to distinguish between the two pairs of subtypes; the second step uses either hsa-miR-200c with hsa-miR-139-5p to identify oncocytoma from chromophobe, or hsa-miR-31 with hsa-miR-126 to identify conventional from papillary tumors. The classifier was tested on an independent set of FFPE tumor samples from 54 additional patients, and identified correctly 93% of the cases. Validation on qRT-PCR platform demonstrated high correlation with microarray results and accurate classification. MicroRNA expression profiling is a very effective molecular bioassay for classification of renal tumors and can offer a quantitative standardized complement to current methods of tumor classification.