99 Clinicopathologic Spectrum of Cystic Hypersecretory Breast Lesions and Ki-67 Index Analysis

Design: We conducted a retrospective analysis of 1385 stage II and III invasive breast cancers (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015).Histopathologic data and tumor infiltrating lymphocytes (TILs) were recorded.Cases were evaluated using the NanoString BC360 gene expression assay for intrinsic molecular subtype (PAM50) and differential gene expression.Cases were then stratified into quintiles based on level of PTEN expression and features were compared for cases with the lowest PTEN expression and those with the highest PTEN expression.Results: Comparing cases with the lowest quintile PTEN expression ("low PTEN") with those in the highest quintile ("high PTEN"), low PTEN was most common in basal-like tumors (151/ 191, 80%), followed by HER2-enriched (69/113, 61%), luminal B (45/125, 36%), and luminal A (11/123, 9%) tumors.Across all four subtypes, low PTEN tumors showed high histologic grade (82% grade III, 18% grade II), high nuclear grade (88% grade 3, 12% grade 2) and high mitotic score (66% score 3, 22% score 2, 12% score 1)).In contrast, high PTEN tumors were predominantly histologic grade II, nuclear grade 3, and had a low mitotic score.Low PTEN tumors were associated with higher TILs (11% >60% TILs, 29% 20-60% TILs and 60% <20% TILs) and high PTEN tumors were associated with lower TILs.Conclusions: Low PTEN gene expression is most often seen in tumors with high histologic grade, high nuclear grade and high mitotic score and is strongly associated with the basal-like PAM50 subtype.At the current time, the PI3K/AKT inhibitor capivasertib is approved only for the treatment of advanced hormone receptor-positive HER2-negative breast cancer.The very high rate of low PTEN expression within the basal-like and HER2E subtypes supports further investigation of a possible role for PI3K/AKT pathway inhibitors in the treatment of non-luminal breast cancers.