Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial

Jeremy St John Thomas, Elena Provenzano, Louise Hiller, Janet Dunn, Clare Blenkinsop, Louise Grybowicz, Anne-Laure Vallier, Ioannis Gounaris, Jean Abraham, Luke Hughes-Davies, Karen McAdam, Stephen Chan, Rizvana Ahmad, Tamas Hickish, Stephen Houston, Daniel Rea, Carlos Caldas, John Ms Bartlett, David Allan Cameron, Richard Laurence HaywardHelena Margaret Earl

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9 Citations (Scopus)


The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation of residual cancer burden was a simple and reproducible method of quantifying response to neoadjuvant chemotherapy as demonstrated by performance comparison of the two pathologists.Modern Pathology advance online publication, 26 May 2017; doi:10.1038/modpathol.2017.30.

Original languageEnglish
Pages (from-to)1069-1077
JournalModern Pathology
Early online date26 May 2017
Publication statusE-pub ahead of print - 26 May 2017


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