Estimation of Risk of Recurrence of Early Stage Estrogen Receptor Positive Breast Carcinoma by Surgical and Medical Oncologists and Pathologists Compared to the Oncotype Dx® Recurrence Score.

Abstract

Abstract Background: The decision to use adjuvant chemotherapy in patients with early stage breast cancer is based in part on the estimation of risk of tumor recurrence by physicians, which traditionally relies heavily on tumor size, nodal status and a set of biologic tumor characteristics such as hormone receptor and HER2 expression. The Oncotype DX® assay is a 21-gene expression profile aiming to improve risk stratification, recurrence prediction and optimize selection of patients for adjuvant chemotherapy.Methods: We selected 154 consecutive patients with early stage estrogen receptor (ER) positive breast cancer and available Oncotype Dx® recurrence score (RS) for the study. Clinicopathologic data, including patient age, menopausal status, tumor size, histologic type, grade, mitotic activity, presence of lymphatic invasion (LVI), nodal status, hormone receptor and HER2 status on all patients were provided to four surgical oncologists, four medical oncologists and three pathologists, specializing in breast cancer diagnosis and management. Participants were asked to estimate the risk of recurrence of tumors based on available clinicopathologic data and to provide the three most important tumor features their risk estimates were based on. Risk estimates of participants were compared with RS results.Results: Based on the Oncotype Dx® results, 95 (61.7%), 45 (29.2%) and 14 (9.1%) tumors were of low (RS <18), intermediate (RS 18-30) and high (RS ≥31) risk, respectively. RS values showed a highly significant correlation with tumor grade, mitotic activity, LVI, hormone receptor and HER2 status, while no correlation with patient age, menopausal status, tumor size and histologic type was found. Participants' risk estimates agreed with those of the Oncotype Dx® assay in 54.2 ± 2.3 % (mean ± SEM, range 41.6 - 63.0%) of cases, while the risk of recurrence was over- and underestimated compared to RS results in 31.8 ± 3.1% (16.2 - 43.5%) and 14.1 ± 1.4% (7.1 - 22.7%), respectively. The rates of overestimation were significantly higher than those of underestimation (p = 0.0003). Although medical oncologists tended to overestimate the risk more frequently (38.1 ± 2.0%) compared to surgeons (28.7 ± 5.9%) and pathologists (27.5 ± 7.8%), the difference did not reach statistical significance. Estimation of the agreement of participants' risk assessment with RS results showed a mean kappa value of 0.2955 (range 0.1506 - 0.4123). No statistically significant difference in overall concurrence with RS results was found between surgeons, medical oncologists and pathologists. Participants ranked tumor stage/nodal status, hormone receptor status and tumor size to be the most important features when estimating recurrence risk.Conclusions: Based on traditional clinicopathologic features alone, surgeons, medical oncologists and pathologists tend to overestimate the risk of tumor recurrence as compared to Oncotype Dx® assay results. The RS may provide additional information regarding the intrinsic biological features of ER positive breast cancers and help tailoring treatment recommendations. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4061.