Routine pathologic parameters can predict Oncotype DXTM recurrence scores in subsets of ER positive patients: who does not always need testing?

Abstract

Oncotype DX(TM) is an RT-PCR-based assay used to predict chemotherapy benefit in patients with estrogen receptor (ER) positive breast cancers. We were interested if routinely available pathologic parameters could predict Oncotype DX Recurrence Scores (RS) in subsets of patients. We identified 173 breast cancers with available RSs and used 104 of these as a test set and 69 cases as a validation set. Pathologic characteristics including size, histologic type, Nottingham grade, and lymphatic invasion were recorded. Test set cases were stained for ER, progesterone receptor (PR), HER2, Ki67, CyclinD1, BCL2, D2-40, and P53. Statistical correlations with RS and regression tree analysis were performed. The validation set was subjected to analysis on the basis of grade, PR, and Ki67. In the test set, grade, PR levels and Ki67 had the strongest correlation with RS (P = 0.0002-0.0007). Regression tree analysis showed grade and PR as factors that could segregate cases into RS categories, with Ki67 adding value in certain subsets. A subset of cancers with a high likelihood of having a low RS (0-18) was identified with the following characteristics: grade 1, strong PR expression (Allred score ≥ 5) and Ki67 ≤ 10%. No cases with these characteristics had a high RS (≥ 31) and 73% had a low RS. Cancers highly likely to have a high RS were grade 3, low to absent PR expression (Allred score <5) and Ki67 > 10%. 80% of cases with these characteristics had a high RS and no cases had a low RS. Our validation set had similar findings in these two subsets. In conclusion, When cost and time are a consideration and the added value of Oncotype DX(TM) testing is in question, it may be reasonable to assume the results of this test in two specific subsets of breast cancers: (1) grade 1, high PR, low Ki67 cancers (low RS), and (2) grade 3, low PR, high Ki67 cancers (high RS).

Semi-quantitative immunohistochemical assay versus oncotype DX® qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study

“…Although qualitative hormone receptor results appears to be less commonly affected, this variation in quantification has the potential to impact the overall recurrence score, which according to published literature is heavily affected by tumor hormone receptor content, HER2 status, and proliferation. 2,4,26,27 In summary, our study demonstrates good overall concordance for qualitative ER and PR results when comparing immunohistochemistry to qRT-PCR. However, our results suggest immunohistochemistry is more sensitive for both ER and PR detection.…”

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

“…Although the Recurrence Score was shown to predict outcome and response to therapy when analyzing large numbers of cases, its prognostic/ predictive accuracy in a given individual patient has not been adequately addressed and little has been done to study the possibility that some cases may have a falsely low or high Recurrence Score when compared with what would be expected based on routine pathological features and/or outcome. 44 In addition, the reproducibility of the assay performed with tissue extracts without microdissection of cancer cells from the stroma is not well established, and several studies suggest that the stromal and intimately associated inflammatory cells, especially when mitotically active, can have a significant effect on the Recurrence Score. 3,44,45 It should also be noted that, in part due to the high cost of the test, no studies validating to the reproducibility and utility of the Oncotype DX assay are available that are independent of Genomic Health.…”

“…44 In addition, the reproducibility of the assay performed with tissue extracts without microdissection of cancer cells from the stroma is not well established, and several studies suggest that the stromal and intimately associated inflammatory cells, especially when mitotically active, can have a significant effect on the Recurrence Score. 3,44,45 It should also be noted that, in part due to the high cost of the test, no studies validating to the reproducibility and utility of the Oncotype DX assay are available that are independent of Genomic Health.…”

Comparison of Oncotype DX and Mammostrat risk estimations and correlations with histologic tumor features in low-grade, estrogen receptor-positive invasive breast carcinomas

“…Although both tests were shown to predict outcome and response to therapy when analyzing large numbers of cases, their prognostic and predictive accuracy in a given individual case has not been adequately addressed and little has been done to study the possibility that some cases may have a falsely low-or high-risk prediction when compared with what would be expected based on clinicopathologic features and/or outcome. 17 Furthermore, the reproducibility of the Oncotype DX assay, performed with tissue extracts without microdissection of cancer cells from the stroma, is not well established and several studies suggest that stromal and inflammatory cells can have a significant effect on the Recurrence Score. 2,[17][18][19] Indeed, we have recently shown that a proliferative, cellular stroma and inflammatory cells associated with tumor cells may account for unexpected intermediate-/high-risk estimations by Recurrence Score in low-grade breast carcinomas.…”

“…17 Furthermore, the reproducibility of the Oncotype DX assay, performed with tissue extracts without microdissection of cancer cells from the stroma, is not well established and several studies suggest that stromal and inflammatory cells can have a significant effect on the Recurrence Score. 2,[17][18][19] Indeed, we have recently shown that a proliferative, cellular stroma and inflammatory cells associated with tumor cells may account for unexpected intermediate-/high-risk estimations by Recurrence Score in low-grade breast carcinomas. 19 In contrast, the immunohistochemistry based Mammostrat assay examines only cancer cells and its results are not affected by the presence of inflammatory cells or the features of tumor stroma.…”