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Oncotype DX Utility Disputed in Correspondences to NEJM


NEW YORK (GenomeWeb) – Members of two European teams have expressed reservations about the conclusions of a study published online in the New England Journal of Medicine in November, which supported the clinical utility of Genomic Health's Oncotype DX to guide treatment for women with a relatively low-risk breast cancer subtype.

For that Oncotype DX study, led by Montefiore Medical Center's Joseph Sparano, researchers involved in the "Trial Assigning Individualized Options for Treatment" (TAILORx) study used the 21-gene expression signature to estimate breast cancer recurrence risk for almost 10,300 women with a relatively low-risk breast cancer subtype characterized by hormone-receptor positive, human epidermal growth factor receptor 2-negative, axillary node-negative status.

In the 1,626 women from that group who had the lowest risk scores, they saw an overall survival rate of 98 percent in the five years following treatment with endocrine therapy alone, rather than endocrine therapy and chemotherapy.

In a correspondence published online in NEJM last night, Institute Bergonié researcher Marc Debled and co-authors presented findings from their retrospective study of available data for 1,235 breast cancer patients classified with standard clinicopathologic features such as tumor size, grade, invasiveness, and expression levels for hormone receptors and/or HER2.

They noted that the five-year, disease-free survival rate in the more than 1,000 women who did not receive chemotherapy based on their clinicopathologic features was just shy of 99 percent. Over the same time frame, that analysis suggested disease-free survival in the group that got endocrine and chemotherapy was nearly 98 percent.

"These results show that standard clinicopathologic criteria are sufficient to spare the use of chemotherapy in a large majority of patients with breast cancer," the team wrote. "We disagree that the study by Sparano and colleagues adds evidence for the use of the Oncotype DX Recurrence Score in this population."

For its part, a trio from the Karolinska Institute described a similar study in its correspondence to NEJM. Theodoros Foukakis and colleagues reportedly analyzed outcomes for nearly 1,000 breast cancer cases treated in Stockholm in 2005 or 2006. They identified 908 cases resembling those included in the TAILORx study that had been assessed using a so-called Ki67 proliferation index, which measures the proportion of tumor cells expressing a protein marker for cell proliferation.

Of the almost 250 women who had tumors with very low Ki-67 proliferation index scores, the team noted that 229 women did not receive adjuvant chemotherapy. In that group, it claimed that survival outcomes were on par with those reported in the endocrine therapy-treated, low recurrence risk score group from TAILORx.

In his response to the critical correspondences, Sparano noted that "clinicopathologic features did not allow a clinician to reliably distinguish patients who had a very low [Oncotype DX] recurrence score from those with higher recurrence score" for tumors assessed in the TAILORx study, suggesting the 21-gene assay provides an additional level of prognostic information.

With respect to the Ki-67 proliferation index findings, meanwhile, Sparano pointed out that groups such as the American Society of Clinical Oncology have recently recommended against using the Ki-67 proliferation index to guide treatment decisions due to inconsistent scoring from one lab to the next, the possibility of variable interpretation, and a lack of fixed cutoff values.