Discordance between oncotype DX recurrence score and RSPC for predicting residual risk of recurrence in ER-positive breast cancer

Abstract

PurposeOncotype DX, a gene expression assay widely employed to aid decision making on adjuvant chemotherapy use in patients with primary oestrogen receptor-positive (ER+) breast cancer, produces a recurrence score (RS) related to distant disease recurrence (DR) risk (RS%). In node-negative patients, RS can be integrated with clinicopathological parameters to derive RS-pathology-clinical (RSPC) that improves prognostic accuracy.MethodsData were collected on patients having clinically indicated tests with an intermediate clinical risk of distant recurrence, and for whom the decision to prescribe chemotherapy remained unclear. Correlation between RS% and RSPC scores was examined. An agreement table was constructed using risk-categorised data. Association between RS%-derived categorical risk assignments and treatment recommendation was evaluated.ResultsData on 171 tests (168 patients) were available. Median DR risk by RS% was 11% (range 3–34%), by RSPC it was 15% (range 4–63%). Correlation between RS% and RSPC was 0.702 (p < 0.001). RS% classified 57.3% of cases as low-, 32.2% intermediate- and 10.5% high-risk for DR; by RSPC proportions were 33.9, 35.7, and 30.4%, respectively. The number of patients receiving chemotherapy recommendations was: 14/87 (16.1%) categorised as low-risk by RS%, 27/49 (55.1%) as intermediate-risk and 12/13 (92.3%) as high-risk. Of 149 patients recommended for endocrine treatment alone, 28 (18.8%) were categorised by RS% as low-risk but by RSPC as intermediate- or high-risk.ConclusionsIn this group of patients, RSPC assessed fewer patients as low-risk and more as high-risk than did RS%. The discordances between the scores indicate that RSPC estimates of risk should be considered when selecting patients for endocrine therapy alone.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-017-4514-z) contains supplementary material, which is available to authorised users.

The impact of Oncotype DX breast cancer assay results on clinical practice: a UK experience

“…Incorporating the revised TAILORx RS cutoffs of < 11, 11-25 and > 25 improved concordance between RS and RSPC to over 70% for the low-and high-RS groups. However, in our study > 50% of patients with intermediate RS (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) were reclassified as either high or low risk by RSPC. The clinical characteristics of the patients in our series differed from that of the majority of patients enrolled in TAILORx: patients in our series were more likely to have tumours > 2 cm in size and/or be Grade 3.…”

“…This is likely to account for the discrepancies between risks as defined by RS vs RSPC in our patient population. Dodson et al also noted that RSPC should potentially be taken into account when deciding if a patient should have adjuvant endocrine therapy alone [15]. However, it should be noted that while high RSPC scores may indicate a higher risk of recurrence, it is not clear whether patients with high-risk RSPC would benefit from chemotherapy as this hypothesis has not been tested in a clinical study.…”

“…Tang et al originally showed that RSPC classified more patients as low risk than RS [14]. However, this is in contrast to data from a contemporary UK patient population [15], which is likely to be due to differences in the clinical characteristics of the patient populations being tested.…”

“…This trial incorporated modified definitions of risk when compared to those defined in the development of Oncotype DX, with low, intermediate and high risk defined as RS of < 11, 11-25 and > 25, respectively [11,12]. In TAILORx, patients with intermediate RS (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) were randomised to endocrine therapy versus chemotherapy plus endocrine therapy [12]. The results demonstrated no significant difference between the two arms for invasive disease-free survival (83.3% vs. 84.3% in the endocrine and chemo-endocrine therapy groups, respectively), disease recurrence and overall survival (93.9% vs. 93.8%) [11].…”

“…Unlike other gene expression arrays, Oncotype DX does not incorporate other clinical or pathological risk factors which are known to be predictors of prognosis, such as tumour size and nodal status. However, RS scores from Oncotype DX can be combined with tumour grade, size and patient age standardised against the type of endocrine treatment used (either an aromatase inhibitor or tamoxifen) to create an integrated risk estimate [14,15]. This produces a combined RS/pathological/clinical (RSPC) risk score, with risk classified as low (< 12%), intermediate (12-20%) or high (> 20%) [14].…”