Clinicopathologic Analysis of Low Grade Invasive Breast Carcinomas (BC) with intermediate and High Oncotype DX Recurrence Scores.
Geza Acs, Nicole N Esposito, Christine Laronga. Ruffolo Hooper & Associates, Tampa, FL; Moffitt Cancer Center, Tampa, FL
Background: Oncotype DX is an RT-PCR based 21-gene molecular assay validated to provide prognostic and predictive information in patients with ER positive, node negative BC. The Oncotype DX Recurrence Score (RS) is divided in to three risk categories as low (<18), intermediate (18-30) and high (>30) risk of distant tumor recurrence at 10 years. Although the RS was shown to correlate with several histopathologic tumor features, there is a significant proportion of cases showing an apparent "discrepancy" between RS and risk estimates based on traditional clinicopathologic tumor features. We analyzed the histopathologic features in low grade BC associated with an RS of >18.
Design: The study included 117 patients with ER positive low grade BC who underwent Oncotype DX testing between 2006-2010. The histopathologic features of the cases were prospectively determined by 2 pathologists (GA and NNE) without knowledge of the RS results. The tumor stroma was evaluated for increased cellularity, presence of inflammatory cells, presence of prior biopsy site and dense fibrosis. Double immunostain for pancytokeratin and Ki67 was performed on representative tumor blocks to assess cell proliferation in tumor versus stromal/inflammatory cells. The clinicopathologic features of BC with RS <18 were compared to those with RS ≥18.
Results: Thirty-seven (32%) and 80 (68%) cases showed RS <18 and ≥18, respectively. We found no significant difference between the two group of BC with regard to patient age, menopausal status, tumor size, tubule formation, nuclear grade, mitotic score, number of mitoses per 10 high power fields, lymphatic invasion, nodal metastasis, percent ER reactivity, HER2 status, presence of biopsy site and dense fibrosis. BC associated with RS ≥18 showed lower percent PR reactivity (p=0.0574), increased stromal cellularity (p=0.0007) and presence of inflammatory cells (p=0.0007). Double immunohistochemical stains showed increased cellular proliferation in stromal/inflammatory cells compared to carcinoma cells in cases associated with a cellular stroma and inflammatory infiltrate.
Conclusions: The presence of increased stromal cellularity and associated inflammatory cells in low grade BC may contribute to an apparently increased risk of recurrence according to Oncotype DX testing. Careful assessment and correlation with histopathologic features in such "discordant" cases may help in determining appropriate patient management.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 1, Wednesday Afternoon