February 5, 2009

Individualizing Treatment Options for Early-stage Breast Cancer Patients

By Lee S. Schwartzberg, M.D., F.A.C.P.

An important advance in the treatment of cancer is the development of more individualized cancer therapy. Information provided by genomic tests or from analysis of other characteristics of cancer cells can often help guide the selection of treatments that have the best chance of success for a particular patient.

Oncotype DX™ is a test that measures the expression of 21 genes in a sample of early stage breast cancer cells. The test is used to calculate a recurrence score, which indicates the likelihood of cancer recurrence. Studies have reported that among women with node-negative, estrogen receptor-positive (ER-positive) breast breast cancer treated with tamoxifen, the recurrence score is a better predictor of recurrence than standard measures such as patient age, tumor size, and tumor grade.1 The recurrence score was also linked with the response to chemotherapy among women with node-negative, hormone receptor-positive breast cancer,2 and can help guide decisions about the need for chemotherapy.

The following are comments from Lee S. Schwartzberg, M.D., F.A.C.P, on individualizing treatment for early-stage breast cancer and the significant role that the Oncotype DX® 21-gene recurrence score assay plays in this approach.

In addition to getting [pathology] testing for the size of their tumor and whether or not there are positive lymph nodes, all patients get tested for the presence of estrogen and progesterone receptors and the presence of over-expression and/or amplification of HER2 [human epidermal growth factor receptor 2]. Using all of these factors together we can now start to individualize treatment options for early-stage breast cancer.

More recently, we have developed the ability to further subtype patients using gene expression testing. The most fully advanced of these tests is the Oncotype DX® 21-gene recurrence score assay. It’s an approved test that has been in the clinic now for several years. In my opinion, it’s very useful in helping to determine what the best therapy is for certain groups of early-stage breast cancer.

The Oncotype DX test is approved for ER-positive, lymph node-negative patients and gives a continuous readout from the 21-gene reverse transcriptase PCR [polymerase chain reaction—a technique used in molecular biology] testing of expression of those genes. It has been validated to show what the 10-year risk of distant recurrence will be based on the recurrence score that is generated from those 21 genes. In practical terms it sorts patients into three groups: low-risk, intermediate-risk, and high-risk.

The benefit of the Oncotype DX test is two-fold: first of all, it’s prognostic, so independent of therapy, it tells what the risk of recurrence will be for that individual tumor; and perhaps more importantly, it is predictive.

Predictive capabilities by recurrence score for Oncotype DX are as follows:

  • For patients who have low recurrence scores, the test is predictive for high benefit from tamoxifen and no benefit from additional chemotherapy over tamoxifen.
  • For patients who have high recurrence scores, it is predictive for limited benefit from tamoxifen and high benefit from chemotherapy.
  • The intermediate group tends to have some benefit from tamoxifen and some benefit from chemotherapy, although the confidence intervals [reliability of estimate] are wide there. The benefit of chemotherapy is not clearly established in the intermediate group. We can use this test to determine whether or not patients will benefit from the addition of chemotherapy to hormonal therapy in a variety of ER-positive, node-negative settings.

At San Antonio [San Antonio Breast Cancer Symposium, December 2007] there were a number of posters that addressed how the use of the Oncotype DX test actually works in the real-world setting. A multicenter prospective study assessed the impact of the assay on patient satisfaction, anxiety, and decisional conflict for adjuvant breast cancer treatment selection.3

  • In general, patients were very open to having the test performed on their tumor.
  • In addition, 27% of women had a change in their adjuvant therapy that was recommended as a direct result of the Oncotype DX score.
  • Patients felt better and were more satisfied with the decision making when they were included in the discussion and decision to use the Oncotype DX test.

The bottom line is that Oncotype DX is an additional, valuable tool in the dialogue between the physician and the patient in terms of reaching the best treatment decision.

A retrospective analysis assessed the impact of using the Oncotype DX test on treatment decisions in a single academic center: The University of Pittsburgh Cancer Institute.4 In this case, they compared the risk score as generated by the NCCN guidelines and they found a big difference between the Oncotype test and how the NCCN sorts women into low- and high-risk groups based on clinical factors. It appeared that the Oncotype test was better able to stratify women into different classes. In addition, they did a cost saving analysis, which suggested that because there were several women who were considered high-risk clinically but were found to be low-risk by Oncotype DX score and therefore did not receive chemotherapy, that there was a net savings by using the Oncotype test in appropriate patients; it offset the cost of the chemotherapy that was not given.


1. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. New England Journal of Medicine. 2004;351:2817-26.2. Paik S, Tang G, Shak S et al. Gene Expression and Benefit of Chemotherapy in Women with Node-Negative, Estrogen Receptor-Positive Breast Cancer. Journal of Clinical Oncology. 2006; 24:3726-34.

3. Mumby PB, Los SS, Norton J et al. Prospective multi-center study of the impact of the 21-gene recurrence score assay on patient satisfaction, anxiety and decisional confluct for adjuvant breast cancer treatment selection. Presented at the 30th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 13-16, 2007. Abstract 1092.

4. Liang H, Brufsky AM, Lembersky BB, Rastogi P, Vogel VG. A retrospective analysis of the impact of oncotype DX low recurrence score results on treatment decisions in a single academic breast cancer center. Presented at the 30th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 13-16, 2007. Abstract 2061.

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Tags: Breast Cancer, Uncategorized