Genomic Health, Inc. announced results from seven new studies focusing on its multigene Oncotype DX breast cancer test, which has helped guide treatment decisions in more than 175,000 breast cancer patients worldwide. The data, presented this past week at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), further confirm the clinical value associated with the Oncotype DX Recurrence Score in accurately predicting chemotherapy benefit and recurrence risk in early-stage breast cancer patients.

“We provide optimal care to breast cancer patients when we treat the underlying biology of their individual tumours,” said Steven Shak, MD, chief medical officer of Genomic Health. “Over the past seven years, multiple studies have established the Oncotype DX Recurrence Score as the most accurate prognostic and predictive measure of the underlying tumour biology, identifying high Recurrence Score and low Recurrence Score disease across the continuum of estrogen receptor-positive breast cancer. The data presented at last week's meeting confirm that traditional clinical, pathologic and biological parameters cannot predict the Recurrence Score.”

Highlights from the seven studies presented this week by Genomic Health and research collaborators include: Meta-analysis of Seven Studies Reinforces Significance of Recurrence Score in Changing Treatment Decisions in Early Stage Breast Cancer. A meta-analysis of seven studies with a total of 912 patients presented in a poster session demonstrated a consistent and large impact of the Recurrence Score on breast cancer adjuvant treatment decisions.

In these studies, physicians who use Oncotype DX in clinical practice changed their treatment decisions in over a third of patients, leading to an overall reduction in chemotherapy use of approximately 28 percent with the use of the Recurrence Score.  It is equally important to note that the Recurrence Score led to the addition of chemotherapy to hormonal treatment in approximately 4 per cent of patients who, prior to the Recurrence Score, were considered low risk but, were subsequently identified as having high Recurrence Score disease. The results of this meta-analysis indicate that the Recurrence Score provides key information for treatment decision-making that cannot be ascertained from traditional measures.

An analysis, presented during a general session on Friday, December 10, showed that the Oncotype DX Recurrence Score used alone remains the recommended method to predict relative chemotherapy benefit in estrogen receptor-positive, node negative breast cancer.  Researchers from the National Surgical Adjuvant Breast and Bowel Project (NSABP), a Pittsburgh-based research network, together with Genomic Health, analyzed the value of the Recurrence Score-Pathology-Clinical (RSPC) risk assessment in predicting chemotherapy benefit.  The RSPC integrates the Recurrence Score and clinical-pathologic factors, including tumour size, tumour grade and age to assess distant recurrence risk in early-stage patients. RSPC has been shown to refine Recurrence Score assessment of distant recurrence risk or prognosis, especially for intermediate risk Recurrence Scores.

The findings demonstrated that the Recurrence Score (interaction p=0.037) predicted chemotherapy treatment benefit, while the RSPC (interaction p=0.10) did not improve prediction of chemotherapy benefit over Recurrence Score alone.  Neither tumour size (interaction p=0.32), tumour grade (interaction p=0.65) nor patient age (interaction p=0.22) was a significant predictor of chemotherapy benefit. Thus, while incorporation of traditional clinical and pathologic factors can improve the prognostic value of the Recurrence Score, these factors do not improve the ability of the Recurrence Score to predict relative chemotherapy benefit.

In a study to determine whether age helps predict individual tumour biology, researchers examined the Oncotype DX Recurrence Score and the molecular expression of estrogen receptor, progesterone receptor , HER2, and the proliferation-related genes among 145,236 estrogen receptor-positive breast cancers. While study findings presented in a poster session showed that the Recurrence Score is slightly higher in breast cancers from younger patients (<40 years old) and lower in older patients (>70 years old), a wide range of Recurrence Score results were observed in all age groups. The results demonstrate the importance of standardized quantitative gene expression measurement delivered by the Recurrence Score, and that patient age alone does not capture the differences in the underlying individual tumour biology as the Recurrence Score does.

Initial data from the prospective, multi-centre West German Study Group (WSG) Plan B trial presented in a poster session examined the relationship between tumour grade and the tumour immunohisto-chemistry biomarker, Ki-67, and the Oncotype DX Recurrence Score. As reported previously, there was a very weak correlation between central grade and the Recurrence Score as well as between Ki-67 and the Recurrence Score (correlation coefficients less than 0.40 for both). There were many patients with high grade and/or high Ki-67 and low Recurrence Score values.

Neither tumour grade nor Ki-67 can predict the Recurrence Score status. An additional analysis of preliminary data from the WSG Plan B trial was presented in a separate poster session, and for the first time, compared risk groups using the Oncotype DX Recurrence Score and the invasion markers uPA (urokinase-type Plasminogen Activator) and its inhibitor PAI-1 (Plasminogen Activator Inhibitor 1). uPA/ PAI-1 was available in 131 of the 1,534 patients who had Recurrence Score results.

Preliminary findings demonstrated a weak correlation between both uPA and PAI-1 and the Recurrence Score (correlation coefficients less than 0.30 for both). These initial results indicate that uPA/PAI-1 cannot predict the Recurrence Score. Additional recruitment and outcome assessment of the ongoing multicenter WSG Plan B trial will address the clinical significance of these initial findings.


“Based on my experience using Oncotype DX in clinical practice for the past six years, it is clear that by using only standard pathology variables, you often cannot predict the Recurrence Score without this well validated, standardized quantitative gene expression test,” said Kathy S. Albain MD, FACP, Professor of Medicine, Division of Haematology/Oncology, Department of Medicine, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Centre, Loyola University Health System, Maywood, Il.

“Just as it is critical to identify every HER2 and estrogen receptor-positive breast cancer patient for treatment selection, it is equally important to identify every patient with high Recurrence Score disease so that they can be considered for chemotherapy, and every patient with low Recurrence Score disease so that they can avoid chemotherapy and consider treatment with hormonal therapy alone” she further added.

In addition to the studies highlighted above, Genomic Health presented findings from two other analyses in poster sessions at SABCS, including: A study analyzing the patterns of gene expression measured by Oncotype DX observed in classic and variant forms of lobular carcinoma in estrogen receptor-positive breast cancer patients identified a wide variation in gene expression in each histologic subtype. A study evaluating whether the Oncotype DX Recurrence Score evolves following exposure to neoadjuvant chemotherapy suggests that use of the test to provide prognostic information for breast cancer recurrence in this setting warrants further study.

The Oncotype DX breast cancer test is the first and only multigene expression test to be included in the published guidelines of both the American Society of Clinical Oncology and the National Comprehensive Cancer Network, to predict the likelihood of chemotherapy benefit as well as recurrence, for patients with node-negative breast cancer that is estrogen-receptor positive and/or progesterone-receptor positive. Additionally, physicians use Oncotype DX to make treatment recommendations for certain node-positive breast cancer patients, and the test report also provides quantitative scores for select individual genes.

Oncotype DX has been extensively evaluated in thirteen clinical studies involving more than 4,000 breast cancer patients worldwide, including a large validation study published in The New England Journal of Medicine and a chemotherapy benefit study published in the Journal of Clinical Oncology. Both Medicare and private health plans covering over 90 percent of US insured lives provided reimbursement for Oncotype DX for patients with node-negative breast cancer that is estrogen-receptor positive and/or progesterone-receptor positive through contracts, agreements or policy decisions.

Genomic Health, Inc. is a molecular diagnostics company focused on the global development and commercialization of genomic-based clinical laboratory services for cancer that allow physicians and patients to make individualized treatment decisions.