According to results recently presented at the 2006 annual San Antonio Breast Cancer Symposium (SABCS), Oncotype DX more accurately predicted estrogen receptor (ER) status when compared to immunohistochemistry or ligand binding (LB) testing for ER status among node-negative breast cancer patients.[1] In addition, quantitative analysis by Oncotype DX of ER and progesterone-receptor (PR) status demonstrates differing prognosis and prediction of benefit from Nolvadex® (tamoxifen) in this patient population.[2]

Adjuvant chemotherapy and/or endocrine therapy have resulted in an improvement in survival in women with early-stage breast cancer. However, the benefit from adjuvant chemotherapy in this group of patients is not uniform, as it is estimated that approximately 85% of women with this disease receive adjuvant chemotherapy that will not ultimately improve their outcomes. Therefore, it is crucial to determine which patients with early breast cancer are at a high risk of developing a recurrence so that individualized adjuvant treatment can reduce the risk of death in appropriately selected patients, while sparing low-risk patients from unnecessary toxicities and medical expenses. While tumor markers have provided some advances in predicting prognosis, it appears that the most promising predictive results may be generated from gene expression profiles.

Oncotype DX is a CLIA-approved reverse-transcription polymerase chain reaction (RT-PCR) test that may be useful in determining which patients with newly diagnosed, stage I or II, node-negative, estrogen receptor-positive breast cancer require adjuvant chemotherapy in addition to anti-estrogen therapy. Oncotype DX predicts the risk of a patient experiencing a recurrence 10 years following diagnosis utilizing formalin-fixed paraffin-embedded tumor tissue. Oncotype DX comprises a panel of 21 genes (16 cancer-related genes and 5 control genes), derived from 3 studies, to accomplish a recurrence-score algorithm. Oncotype DX also helps predict the likelihood of the benefit of adjuvant chemotherapy in these patients.

Results from previous trials have also demonstrated that Oncotype DX may help predict anti-cancer responses to neoadjuvant chemotherapy with Taxotere® (docetaxel) as well as changing treatment decisions in at least one-quarter of women with early breast cancer. Oncotype DX is already covered by Medicare for eligible patients and continues to be evaluated in clinical trials to further define its role.

Estrogen receptor status is an important component in determining optimal treatment for patients with breast cancer. However, the power of different testing methods for ER expression, such as IHC or LB testing varies considerably. 

The first study presented at 2006 SABCS was conducted by researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project (NSABP) to evaluate the effectiveness of results from Oncotype DX in accurately measuring ER expression. This trial included 297 node-negative, ER-positive breast cancer patients who had already received treatment with Nolvadex® (tamoxifen) in the prior NSABP B-14 study. The NSABP B-14 trial had randomized node-negative, ER-positive breast cancer patients to Nolvadex or placebo. 

To test for ER expression, study sites had performed LB testing for ER at the time of patient enrollment, the NSABP Foundation Laboratory performed IHC with the DakoCytomation ER/PR pharmDx, and one of the genes from the 21-gene panel of OncotypeDX was used. The time to a distant recurrence among patients was an endpoint used to measure the accuracy of ER expression among the 3 tests. 

Higher ER expression with all three testing methods was associated with a greater time to a distant recurrence.

Quantitative measurement from Oncotype DX had the strongest association with time to cancer recurrence of all the three testing methods; p<0.0001 for Oncotype DX; p=0.003 for IHC; p=0.045 for LB testing. 

The researchers concluded that results from Oncotype DX are more accurate in quantifying ER expression than IHC and LB in node-negative breast cancer patients. One of the researchers stated that “results from this study suggest Oncotype DX may be the most precise way to measure this widely used biomarker, and could possibly expand how we use the Oncotype DX assay in the future.” 

A second study presented at the 2006 SABCS evaluated the prognostic and predictive associations between ER and PR analysis of Oncotype DX. This study included the examination of results from the NSABP-14 trial and the Kaiser Oncotype DX studies.  The Kaiser study included node-negative breast cancer patients in which the association of gene expression and breast cancer death were evaluated.

In ER-positive patients in both the NSABP and Kaiser studies, the level of expression of ER is significantly predictive of benefit from Nolvadex, but is not significantly associated with the prognosis of untreated patients.

The level of PR expression is not significantly predictive of benefit from Nolvadex, but is significantly associated with the prognosis of patients. 

The researchers concluded that quantitative ER and PR expression as measured through Oncotype DX provide different and distinct associations with the prognosis and prediction of the benefit from Nolvadex among patients with node-negative breast cancer.

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