Background. We conducted a validation study of digital pathology for the quantitative assessment of tissue-based biomarkers with immunohistochemistry. Objective. To examine observer agreement as a function of viewing modality (digital versus optical microscopy), whole slide versus tissue microarray (TMA) review, biomarker type (HER2 incorporating membranous staining and Ki-67 with nuclear staining), and data type (continuous and categorical). Methods. Eight pathologists reviewed 50 breast cancer whole slides (25 stained with HER2 and 25 with Ki-67) and 2 TMAs (1 stained with HER2, 1 with Ki-67, each containing 97 cores), using digital and optical microscopy. Results. Results showed relatively high overall interobserver and intermodality agreement, with different patterns specific to biomarker type. For HER2, there was better interobserver agreement for optical compared to digital microscopy for whole slides as well as better interobserver and intermodality agreement for TMAs. For Ki-67, those patterns were not observed. Conclusions. The differences in agreement patterns when examining different biomarkers and different scoring methods and reviewing whole slides compared to TMA stress the need for validation studies focused on specific pathology tasks to eliminate sources of variability that might dilute findings. The statistical uncertainty observed in our analyses calls for adequate sampling for each individual task rather than pooling cases.

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BackgroundOptimal evaluation and management of the axilla following neoadjuvant chemotherapy (NAC) in patients with node‐positive breast cancer remains controversial. The aim of this study was to examine the impact of receptor phenotype in patients with nodal metastases who undergo NAC to see whether this approach can identify those who may be suitable for conservative axillary management.MethodsBetween 2009 and 2014, all patients with breast cancer and biopsy‐proven nodal disease who received NAC were identified from prospectively developed databases. Details of patients who had axillary lymph node dissection (ALND) following NAC were recorded and rates of pathological complete response (pCR) were evaluated for receptor phenotype.ResultsSome 284 patients with primary breast cancer and nodal metastases underwent NAC and subsequent ALND, including two with bilateral disease. The most common receptor phenotype was luminal A (154 of 286 tumours, 53·8 per cent), with lesser proportions accounted for by the luminal B–Her2 type (64, 22·4 per cent), Her2‐overexpressing (38, 13·3 per cent) and basal‐like, triple‐negative (30, 10·5 per cent) subtypes. Overall pCR rates in the breast and axilla were 19·9 per cent (54 of 271 tumours) and 37·4 per cent (105 of 281) respectively. Axillary pCR rates were highest in the Her2‐overexpressing group (27 of 35, 77 per cent) and lowest in the luminal A group (35 of 153, 22·9 per cent) (P < 0·001). Nodal burden (median number of positive nodes excised) was lower in the Her2‐overexpressing group compared with the luminal A group (0 versus 3; P < 0·001).ConclusionHer2 positivity was associated with increased rates of axillary pCR and reduced nodal burden following NAC.