Prosigna® breast cancer assay: histopathologic correlation, development, and assessment of size, nodal status, Ki-67 (SiNK™) index for breast cancer prognosis

The Prosigna (R) assay is a United States Food and Drug Administration (US-FDA) cleared molecular test for prognostic use in hormone receptor-positive stage I/II breast cancer in postmenopausal women. We analyzed histopathologic features of 79 cases with Prosigna (R) assay results and found a significant correlation between tumor size, grade, and Ki-67 labeling index with Prosigna (R) score (0-40, 41-60, and 61-100) and Prosigna (R) risk categories. Since the Prosigna (R) risk stratification is influenced by lymph node status, we designed an index that included lymph node status and the two most correlated variables (size and Ki-67 labeling index). This was termed the size, nodal, and Ki-67 (SiNK (TM)) index and is calculated as follows: (size in mm) + (pN x 10) + (Ki-67 labeling index). The SiNK (TM) index was divided into <= 40 and >40 to test its prognostic significance in a well-characterized dataset of 106 ER+/HER2-negative stage I-II invasive breast cancers treated with standard multi-modality therapy with long term follow-up (average 101 months follow-up). Patients with SiNK (TM) <= 40 showed significantly improved distant recurrence-free survival (96% distant recurrence-free survival in SiNK (TM) <= 40 compared to 81% in SiNK (TM) >40; log-rank testpvalue: 0.0027). SiNK (TM) provides strong prognostic information in ERo+/HER2-negative breast cancers. SiNK (TM) index is simple to calculate using data from routine pathology reports. This should be further evaluated in larger datasets.