Impact of Oncotype DX on Treatment Decisions in ER-Positive, Node-Negative Breast Cancer with Histologic Correlation

Abstract

Oncotype DX, a gene-expression profiling assay, provides stratification of patients with estrogen-receptor positive, lymph-node-negative early breast cancer into risk groups based on recurrence score, which are associated with distant recurrence and response to chemotherapy. This study aims to determine whether Oncotype DX influences clinicians' treatment decisions, and whether assay results correlate with histologic assessment. Fifty patients with estrogen-receptor positive, node-negative early breast cancer analyzed by Oncotype DX and operated on by two breast surgeons were included. To assess effect on treatment decisions, clinical vignettes were created by retrospective chart review. Physicians were then presented with the clinical vignettes and instructed to make a treatment decisions (i.e., hormone therapy alone versus hormone therapy combined with chemotherapy) both before and after knowledge of the recurrence score. To assess correlation with histologic assessment, a prospective, blinded review of tumor slides was performed by two pathologists. Based on this review, tumors were placed into low, intermediate and high risk groups for comparison with Oncotype DX assay results. Treatment decisions were changed based on Oncotype DX results in 36 and 18% of cases by breast surgeons and medical oncologists, respectively. All tumors categorized as high risk by Oncotype DX were categorized as high risk based on histologic assessment, and 96% of cases categorized as low risk by recurrence score were categorized as low or intermediate risk by histologic assessment. Oncotype DX significantly influences management of estrogen-receptor positive, lymph-node-negative early breast cancer. Further studies are needed to assess association of histologic categorization to assay results.

Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score

“…The risk categories used by the Oncotype DX recurrence score (low (o 18), intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), or high (430)) were applied to the modified Magee recurrence score, and the modified Magee recurrence scores were compared with their paired Oncotype DX recurrence scores for correlation (Pearson correlation) and concordance. We compared the average modified Magee recurrence score, ER, PR, and Ki-67 values at several cutoff points to determine how they stratified into the high and low Oncotype DX recurrence score risk stratification groups.…”

“…14 Oncotype DX uses quantitative reverse transcription-polymerase chain reaction and an algorithm to calculate a recurrence score, giving the highest weight to proliferation (which includes Ki-67), followed by HER-2, ER, and PR. The Oncotype DX recurrence score is reported as a number that is divided into either low (o 18), intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), or high (430) recurrence risk categories.…”

“…[15][16][17][18][19][20][21][22][23][24][25][26][27] Four of the 16 genes (ER, PR, HER-2, and Ki-67) measured as parts of the Oncotype DX panel are routinely assessed at the protein level by immunohistochemistry 28 in the routine diagnostic evaluation of breast cancer. Four linear regression analysis equations (Magee equations) have been published 15,16 using several histopathologic variables, and semiquantitative results from these four immunophenotypic markers (ER, PR, HER-2, and Ki-67).…”

Did Oncotype DX® Recurrence Score Accurately Predict the Risk of Recurrence in Breast Cancer? A 10 Year Period Study in a Single Institution

“…Only three of these patients had received chemotherapy, one from each risk group, respectively. [12]. The investigators found that all cases in their study group that were categorized as high risk by the RS were categorized as high risk based on the pathologist's assessment as well, and that the vast majority of the cases that were categorized as low or intermediate risk by RS were also categorized as low or intermediate risk by the pathologist (96%).…”

“…They found that grade 1, high PR positivity, low Ki-67 breast cancers correlated well with low RS stratified patients and grade 3, low PR, high Ki-67 breast cancers correlated well with high RS stratified patients [11]. Additional studies on specific pathologic features have been shown to correlate with the 21-gene RS, including histologic features, mitotic count, and hormonal receptor expression [12,[18][19][20][21]. In a 2011 study by Cuzick et al, the authors showed that all four of the IHC markers, ER, PR, Ki-67, and HER2 provided independent prognostic information in the presence of classical clinico-pathologic factors including age, nodal status, tumor size, grade and endocrine treatment [9].…”