Wednesday, November 2, 2011

Oncotype DX for Breast Cancer: October News and Research

The Oncotype DX Breast Cancer Assay has been the subject of several recent studies. Topics include how the Oncotype DX compares to and affects doctor assessment of risk, how it compares to other markers and how well it quantifies HER2 status. Today we'll highlight the seven most recent studies. Links may be found on the Oncotype DX page of our website.

A little background

The Oncotype DX Breast Cancer Assay is a test used to assess the risk of breast cancer recurrence in women with early-stage, estrogen-receptor positive, node-negative tumors. The Recurrence Score, which is calculated based on the expression of 21 genes, may help with the decision on whether to pursue chemotherapy. For example, patients with a very low risk of recurrence may decide that the small potential benefit from chemotherapy may not be worth the risk of side effects.

In addition to the Recurrence Score, the Oncotype DX report includes quantitative scores that reflect estrogen receptor (ER), progesterone receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) gene expression. This data may assist with decisions on whether to treat with hormonal therapy, such as tamoxifen, or anti-HER2 drugs, such as Herceptin.

Comparing Oncotype DX to doctors' assessment of risk

In a classic man versus machine match-up, two recent studies in The Oncologist explored how doctor assessment of risk compared to the Oncotype DX Recurrence Score and whether the Recurrence Score changes treatment decisions.

In the first, published online September 20, six academic oncologists predicted whether various pathological scenarios would receive low, intermediate or high Oncotype DX Recurrence Scores. As a whole, the oncologists were able to accurately predict the high risk scores, but were less able to distinguish between low and intermediate risk scenarios. In addition, when the actual Recurrence Scores were provided, treatment decisions changed in 19% of the cases. The authors noted that additional studies are needed to assess whether changes in treatment decisions affect outcomes.

In the second study, dated October 20, four surgeons, four medical oncologists and four pathologists estimated recurrence risk and made treatment recommendations for 154 patients based on pathology data. The medical professionals' estimations agreed with the Oncotype DX Score in 54% of the cases. The professionals tended to overestimate risk compared to the Recurrence Score. The authors concluded that the Recurrence Score "provides useful information that improves patient selection for chemotherapy and changes treatment recommendations in approximately 25% of cases."

How accurate is the Oncotype DX HER2 status score?

As mentioned above, in addition to the Recurrence Score, the Oncotype DX provides a score to quantify HER2 expression. An October 11 Journal of Clinical Oncology study found "an unacceptable false-negative rate" for HER2 status. published a video and story about the study on October 24.

The study used standard IHC and FISH HER2 testing to check the quality of the Oncotype DX HER2 status score for 843 patients. Of the 784 patients negative by IHC/FISH, 779 (99%) were also negative by Oncotype. However, all of the 23 patients deemed equivocal by IHC/FISH were classified as negative by Oncotype. Of the 36 positive by IHC/FISH, only 10 (28%) were classified as positive by Oncotype, 12 (33%) were reported as equivocal and 14 (39%) as negative.

The authors concluded that the high false-negative rate "could create confusion in the decision-making process for targeted treatment and potentially lead to mismanagement of patients with breast cancer if only GHI [Genomic Health] HER2 information is used."

How does IHC4 compare to Oncotype DX?

There's been some buzz in the UK about an alternative to the Oncotype DX. An October 19 article in The Telegraph (UK) discussed an IHC4 test, noting that it could be available in as little as a year, and "should cost a tenth" of the Oncotype DX in the UK.

What's the buzz about?

An October 11 study in the Journal of Clinical Oncology compared the Oncotype DX Recurrence Score to an IHC4 prognostic model, which used estrogen receptor (ER), progesterone receptor (PR), Ki-67 and HER2 status from standard IHC testing. IHC stands for 'Immunohistochemistry,' a very common (and inexpensive) test used to analyze the amounts of those four proteins in a biopsy sample.

In the study, all four IHC markers provided independent prognostic information. Combined in the IHC4 model, the information was similar to the Oncotype DX Recurrence Score, with "little additional prognostic value" seen by combining IHC4 and the Recurrence Score.

The study suggested that "the amount of prognostic information contained in four widely performed IHC assays is similar" to that in the Oncotype DX Recurrence Score. The authors noted that further studies are needed to "determine the general applicability of the IHC4."

In the UK, the National Institute for Health and Clinical Excellence (NICE) is reviewing several genetic risk assessment tests to make recommendations for the National Health System (NHS). The Oncotype DX and IHC4 are included, as well as the MammaPrint test, Breast Cancer Index and others. (Link to review protocol.)

How does Ki-67 expression compare to Oncotype DX?

Ki-67 expression is one of the 21 factors considered in the Oncotype DX Recurrence Score. An October 4 study in the British Journal of Cancer, noting that Ki-67 testing "is less expensive than Oncotype DX," compared the two values for 53 patients. The study found a "strong linear correlation" between the two scores. All patients with low Ki-67 were low to intermediate risk with Oncotype DX. All with high Ki-67 were high or intermediate with Oncotype DX. The authors concluded that Ki-67 status is a "major, but not the sole determinant of Oncotype Dx score."

Can additional data improve the Oncotype DX?

An October 17 Journal of Clinical Oncology study found that supplementing the Oncotype DX score with other factors such as tumor size and patient age "refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk." However, the additional information "did not seem to enhance the value" of the Recurrence Score in terms of predicting chemotherapy benefit.

Oncotype DX report format may be difficult to understand

Finally, an October 1 Breast Cancer Research and Treatment study asked if the current Oncotype DX report format is "a good approach for communicating results to patients." Compared to other sample reporting formats, the standard report was more difficult to understand and interpret. The authors suggest that a less complex report might be more effective in communicating test results to patients.

These are only the seven most recent studies on the Oncotype DX assay for breast cancer. For two years of news and research, plus general overviews, please check the Oncotype DX page of our website. From the home page, click the Treatments tab and search for 'Oncotype' in the search box on the top right of the page.

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