Table 19Clinical Utility, Oncotype DX™

Study, YearPopulation size, NEnd Points and Major FindingsComments
Chang, 200755Population: 72/97 eligible patients, (mean age 48.5 y, ER+: 69.1%;TG-Well: 2.8%; TG-Poor: 56.9%, LN-: 90%, HER-2+: 13.5%, treated with docetaxel)End points: prediction of clinical response (by the RECIST method) to docetaxel treatment in women with breast cancerThe authors concluded that Oncotype DX can be potentially be used as a predictive test of chemosensitivity using small amounts of routinely processed specimens
Exclusion criteria: NRClinical validity and utility results:
Clinical CR was more likely in the high RS risk group (P = 0.008); A 50 units increase in the RS showed an OR = 5 (95% CI = 1.3–6.0); AUROC = 0.73;
Gianni, 200549Population: 89/95 patients (mean age 49.9 y, stage-T4b: 79%, stage-T4d: 18%, stage-T2: 1%, stage-T3: 2%, ER+: 58%, TG-1: 24%, TG-3: 21%, LN-: 16%, adjuvant with doxorubicin/paclitaxel followed by paclitaxel)End points (goal): to examine the correlation between RS and pCR, and to identify additional genes associated with pCRThe authors showed that the RS was strongly correlated with pCR, and identified a set of genes, whose expression correlated with pCR to neoadjuvant doxorubicin and paclitaxel
Exclusion criteria: NRClinical validity and utility results:
The global likelihood ratio test assessing probit regression based models with and without the incorporation of the RS resulted in a P value of 0.005
Habel, 200650Population:End points: The risk of breast cancer-specific mortality among women with ER+, LN- breast cancer. Patients were matched by age, race, year of diagnosis and tamoxifen treatment.The authors showed that the RS was strongly associated with risk of breast cancer death among:
220/234 eligible cases (TG-Well: 11%, TG-Poor: 47%, TS < 2: 64%, TS >2cm: 36%, ER+: 76%, ER-: 24%)Clinical validity and utility results: ER+ patients treated with tamoxifen;
570/631 eligible control patients (TG-Well: 31%, TG-Poor: 23%, TS < 2: 79%: TS >2cm: 21%, ER+: 90%)10 y death risk according to RS (with tumor size and grade): ER+ patients not treated with tamoxifen
Exclusion criteria: LN+, age >75 y, initially treated with chemotherapy, inflammatory or bilateral cancer, metastases, prior invasive cancer, unknown/unconfirmed tamoxifenRS <18 / ER+, tamoxifen: 2.8%, 95%CI: 1.7–3.9; ER- patients
RS <18 / ER+, no tamoxifen 6.2%, 95%CI: 4.5–7.9;Such associations remained after accounting for tumor size and grade. Moreover the RS was able to identify a larger subset of patients with low risk of breast cancer death than it was possible with either of these standard prognostic indicators
RS 18–30 / ER+, tamoxifen 10.7%, 95%CI: 6.3–14.9;
RS 18–30 / ER+, no tamoxifen 17.8%, 95%CI: 11.8–23.3;
RS ≥31 / ER+, tamoxifen 15.5%, 95%CI: 7.6–22.8;
RS ≥31 / ER+, no tamoxifen 19.9%, 95%CI: 14.2–25.2;
Mina, 200651Population: 45/70 eligible patients (mean age 49 y, median TS 6.8 cm, TG-Well: 24%, TG-Poor: 49%, ER+: 57%, HER2+: 18%, LN+: 47%, adjuvant with doxorubicin / docetaxel, tamoxifen in ER+);End points: complete pathological response (pCR) to primary chemotherapy with anthracycline- and taxanes;Though the Oncotype DX RS correlated with pCR in the INT Milan cohort of the Gianni et al study,49 this association was not found in the present study
Exclusion criteria: NRClinical validity and utility results:
No correlation between Oncotype DX RS and pCR;
Paik, 200653Population: 651/670 eligible patients (TS < 2: 66%, TG-Well: 13%, TG-Poor: 28%, TS >2cm: 34%, ER+: 100%, LN-: 100%, tamoxifen treatment arm of NSABP B-20)End points: freedom from distant recurrence in women with ER-positive, node-negative breast cancer from NSABP B-20.The RS assay predicts the magnitude of chemotherapy benefit in women with node-negative, ER-positive breast cancer;
Exclusion criteria: specimen shows <5% invasive tumor, insufficient RNA extracted from specimen, weak RT-PCR signal (average cycle threshold for reference genes >35)Clinical validity and utility results:If RS risk groups are considered:
20.6% of the patients RS<18, Tamoxifen, 96.8 93.7% to 99.9%; a minimal benefit from chemotherapy is seen in the low risk group, however with large intervals;
33.5% of the patients RS<18, Chemotherapy, 95.6 92.7% to 98.6%; benefit is not assessable in the Intermediate risk group due to the uncertainty in the estimates;
7% of the patients RS >18 <31, Tamoxifen: 90.9 82.5% to 99.4%; a large chemotherapy benefit is seen in the high risk group
13.7% of the patients RS >18 <31, Chemotherapy: 89.1 82.4% to 95.9%;
7.2% of the patients RS>31, Tamoxifen: 60.5 46.2% to 74.8%;
18% of the patients RS>31, Chemotherapy: 88.1 82.0% to 94.2%;

ER = estrogen receptor; TG = tumor grade; LN = lymph node; HER = human epidermal growth factor receptor; NR = not reported: RECIST = response evaluation criteria in solid tumors; CR = complete response; RS = recurrence score; OR = odd ratio; CI = confidence interval; AUROC = area under Receiver operator curve; pCR = pathological complete response; TS = tumor size; RT-PCR = reverse transcriptase polymerase chain reaction; INT = Italian National Cancer Institute of Milan, Italy; NSABP = The National Surgical Adjuvant Breast and Bowel Project.

From: 3, Results

Cover of Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes
Impact of Gene Expression Profiling Tests on Breast Cancer Outcomes.
Evidence Reports/Technology Assessments, No. 160.
Marchionni L, Wilson RF, Marinopoulos SS, et al.

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