Oncotype DX Breast Cancer Test: Now for DCIS Too

But Is Radiation Helpful or Not?

Nick Mulcahy

December 07, 2011

December 7, 2011 (San Antonio, Texas) —The Oncotype DX breast cancer test (Genomic Health), the predictive 21-gene assay used in invasive breast cancer, will soon be available for use in patients with ductal carcinoma in situ (DCIS).

New data on use of the test in DCIS were presented here at the 34th Annual San Antonio Breast Cancer Symposium.

The Oncotype DX test uses genetic information in breast cancer tissue to predict the risk for recurrences. It is already marketed for use in invasive cancer, where it identifies women who might be able to forgo chemotherapy because of their low risk for recurrence. Now the test has been developed for use in DCIS, where it might help identify patients at low risk for recurrence who can be spared radiation therapy.

In the case of DCIS, the test only uses information from 12 genes; the other 9 genes in the 21-gene assay are not applicable to DCIS.

In a new study, the 9-gene assay predicted 10-year risk for local recurrence in patients with DCIS who were treated with lumpectomy alone, without radiation therapy.

Local recurrence was defined as either a new invasive breast cancer or the recurrence of DCIS in the same breast (ipsilateral breast event).

A DCIS recurrence risk score should help clinicians and patients decide about the need for radiation therapy, suggested the lead author of the study, Lawrence J. Solin, MD, chair of the Department of Radiation Oncology at the Albert Einstein Medical Center in Philadelphia, Pennsylvania.

"The DCIS score provides a new clinical tool to guide treatment selection," he said at a meeting press conference.

Radiation therapy has been shown to reduce local recurrence risk, said Dr. Solin. However, there are no "reliable" methods to determine whether patients can safely forgo radiation and be treated with surgery alone, he explained.

An expert not involved with the study pointed out that the gene assay has a limitation — it does not let patients know if they will benefit from radiation. "It just tells us what the recurrence risks are in patients who don't have radiation. It doesn't necessarily tell us the benefit of radiation therapy," said Benjamin Smith, MD, assistant professor of radiation oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Smith's point is that the assay can provide insight into an individual's risk for local recurrence when undergoing lumpectomy alone, but offers no insight into the benefit of choosing to receive radiation — even if the test reveals a high risk for recurrence.

Nevertheless, the study is "powerful," said Minetta Liu, MD, associate professor of medical oncology at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. That's because "the study team had clinical outcomes linked to tissue specimens," she said. But it is a single study and further validation is needed, said Dr. Liu, who also pointed out that the study represents the "first time that a molecular tool has been used in precancer."

Dr. Solin said that Genomic Health plans to launch the test at the end of December, pending approval from CLIA (Clinical Laboratory Improvement Amendments). A company spokesperson said that the product launch is very simple on the clinical end. New order forms for the test will be distributed on December 28; clinicians can mark a box for an invasive breast cancer score or for a DCIS score.

The DCIS test costs $4175, according to Genomic Health. Radiation therapy costs, on the other hand, range from a minimum of $8000 when covered by Medicare to upwards of $25,000 when covered by private insurance, depending on a number of variables, said Dr. Smith.

About 45,000 patients are newly diagnosed with DCIS each year in the United States, accounting for approximately 1 of every 5 new cases of breast cancer. "We overtreat a lot of them," said C. Kent Osborne, MD, a codirector of the meeting, in an interview with Medscape Medical News. He is director of the Dan L. Duncan Cancer Center at the Baylor College of Medicine in Houston.

Local recurrences of DCIS or a new invasive breast cancer occur in 20% to 25% of patients at 10 years, on average, with surgery alone, according to Genomic Health. The addition of radiation therapy for DCIS has not been shown to prolong survival, added Dr. Solin.

Study Details

This study is a retrospective analysis that used data from the 670-patient Eastern Cooperative Oncology Group E5194 study, which compared outcomes in DCIS patients treated with surgery alone with those in patients treated with surgery plus radiation. About a third of the patients also received tamoxifen.

The study revealed the 10-year risk for a subset of 327 patients with DCIS treated with surgical excision (negative margins of at least 3 mm) alone. The patients had low- or intermediate-grade DCIS (2.5 cm or less) or high-grade DCIS (1 cm or less).

The assay was performed with quantitative reverse-transcription polymerase chain reaction, using tumor specimens from the patients. A new, prespecified DCIS score was designed to predict recurrence using an gene-expression algorithm featuring 12 of the genes in the 21-gene Oncotype DX breast cancer assay.

The primary objective of the study was to determine whether there was a significant association between the risk for an ipsilateral breast event and the continuous DCIS score in Cox models.

Among the 327 patients, 46 had an ipsilateral breast event, which was either an ipsilateral local recurrence of DCIS (n = 20) or invasive cancer (n = 26). Median follow-up was 8.8 years. The 10-year ipsilateral breast event rates were 15.4% for low/intermediate-grade DCIS and 15.1% for high-grade DCIS (determined by central pathology review); for an invasive ipsilateral breast event, the 10-year rates were 5.6% and 9.8%, respectively

The continuous DCIS score over the study period was significantly associated with an ipsilateral breast event (hazard ratio [HR], 2.34 per 50 units; 95% confidence interval [CI], 1.15 to 4.59; P = .02) when adjusted for tamoxifen use, and with invasive ipsilateral breast event (HR, 3.73; 95% CI, 1.34 to 9.82; P = .01).

Features associated with an ipsilateral breast event in multivariate models included menopausal status (HR, 0.49; 95% CI, 0.27 to 0.90; P = .02), tumor size (HR, 1.52 per 5 mm; 95% CI, 1.11 to 2.01; P = .01), and continuous DCIS score (HR, 2.41; 95% CI, 1.15 to 4.89; P = .02).

The results also indicated that 75% of the 327 patients had a "low" DCIS score, which was prespecified in the study.

The patients with a low DCIS score had a 12% likelihood of a local recurrence in the study, and a 5% likelihood of developing a new invasive breast cancer. These are the patients who are the best candidates to forgo radiation, said Dr. Solin.

The study also showed that patients with a high DCIS score had a 27% likelihood of local recurrence.

The study was sponsored by Genomic Health. Dr. Solin, Dr. Smith, and Dr. Osborne have disclosed no relevant financial relationships.

34th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S4-6. To be presented December 8, 2011.

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