A second major clinical study validates the Oncotype DX DCIS Score for predicting local recurrence in patients with ductal carcinoma in situ.

The Oncotype DX DCIS Score, a 12-gene assay used to calculate risk of local recurrence of ductal carcinoma in situ (DCIS), has been validated in a second major clinical study.

A noninvasive breast abnormality, DCIS accounts for 30% of newly diagnosed breast cancers. Although DCIS is confined to the milk ducts, it can progress to invasive breast cancer if left untreated. Typically, treatment involves breast-conserving surgery (BCS) often followed by radiation therapy (RT), although patients at low risk of recurrence may forego RT.

“The challenge is that the clinical factors and pathological features of DCIS don't reliably help clinicians identify women at low risk of recurrence, resulting in some patients being overtreated and some being undertreated,” says Eileen Rakovitch, MD, an associate professor and radiation oncologist at Sunnybrook Health Sciences Centre in Toronto, Canada.

A 2013 study in the Journal of the National Cancer Institute showed the Oncotype DX DCIS Score was predictive of local recurrence (same breast) in women who've undergone BCS alone. (Patients are deemed to be at low, intermediate, or high risk of recurrence depending upon their score, which can range from 0 to 100.) That study included 327 women with specified tumor size and grades, and with clear surgical margins.

To validate these results, Rakovitch and colleagues at the Ontario DCIS Study Group in Canada tested the predictive ability of the DCIS Score in a larger, more diverse population. “We included women with larger tumor sizes and smaller margins than the women who participated in the previous clinical trial,” she explains.

The researchers identified 3,335 women in Ontario diagnosed with DCIS between 1994 and 2003 and were able to collect archived tumor tissue from 1,569 confirmed to have pure DCIS (no invasive cancer). Of this group, 718 patients were treated with BCS alone, and 846 were treated with BCS plus RT.

Rakovitch, the study's principal investigator, presented data from the 718 women treated with BCS alone, on December 12 at the 2014 San Antonio Breast Cancer Symposium in Texas. Of these patients, 571 had clear surgical margins. After a median follow-up period of 9.4 years, 100 of the 571 women had a disease recurrence in the same breast (43 DCIS, 56 invasive carcinoma, 1 both DCIS and invasive carcinoma). Those who were classified as having a low-risk DCIS Score were significantly less likely to develop a recurrence of DCIS or invasive cancer (12.7%) compared with patients who had an intermediate-risk or high-risk DCIS Score (33% and 27.8%, respectively).

Rakovitch acknowledged the similar risk of recurrence between the intermediate-risk and high-risk categories, adding that it is uncertain if the test's manufacturer, Genomic Health, will choose to merge the two.

Rakovitch noted similar findings for the 846 patients who received BCS plus RT, although data from that arm of the study are still being analyzed.

The researchers plan to integrate the DCIS Score with established risk factors, such as multifocality, age, and tumor size, to help further stratify DCIS patients who are at low risk and those at high risk. “The goal is to better inform clinicians and patients who are making decisions about treatment options,” says Rakovitch.