SAN ANTONIO – A risk score based on a 12-gene assay is expected to help physicians determine whether postsurgical radiation for ductal carcinoma in situ would improve an individual patient’s outcome, Dr. Lawrence J. Solin reported at the San Antonio Breast Cancer Symposium.
In a biomarker validation study, investigators demonstrated that a prespecified score on the Oncotype DX DCIS measure developed by Genomic Health Inc. can predict the risk of an ipsilateral breast event – either the development of a new invasive breast cancer or the recurrence of DCIS in the same breast – in women who have undergone breast-conservation surgery.
The 12-gene assay is a subset of the Oncotype DX 21 gene assay for invasive breast cancer. Dr. Solin, chair of radiation oncology at Albert Einstein Medical Center in Philadelphia, and colleagues in the Eastern Cooperative Oncology Group (ECOG) evaluated its predictive value in 327 patients drawn from the prospective multicenter ECOG E5194 study in which the more extensive assay had been performed, he explained. All of the patients had low/intermediate grade DCIS, defined as 2.5 cm or smaller or high-grade DCIS, defined as 1 cm or smaller, he said (J. Clin. Oncol. 2009;27:5319-24).
Based on the 21-gene assay, central pathology review, and a recurrence algorithm, the investigators calculated a DCIS score from 0-100, with scores less than 39, 39-54, and 55 and higher, respectively, classified as low, intermediate, and high risk for recurrence, Dr. Solin said. During nearly 9 years of follow-up, recurrent DCIS developed in 20 patients and invasive cancer in the ipsilateral breast in 26 patients, he reported. Among patients with low/intermediate DCIS and high-grade DCIS, respectively, the 10-year breast event rates were 15.4% and 15.1%, and the invasive breast event rates were 5.6% and 9.8%, he reported.
By DCIS score, "75% of the patients were in the low-risk category, compared with 14% classified as intermediate risk and 11% as high risk," said Dr. Solin. The rates of both any ipsilateral breast event and invasive breast cancer were directly related to DCIS risk score, with 12.0%, 24.5%, and 27.3% of patients in the low, intermediate, and high DCIS score groups experiencing any ipsilateral breast event and 5.1%, 8.9%, and 19.1% developing invasive breast cancer, he said. In multivariate analysis, DCIS score, menopausal status, and tumor size were all significantly associated with recurrence.
The DCIS score is "groundbreaking," according to Dr. Solin, because it is the first validated molecular marker that clearly differentiates low-risk from high-risk disease in DCIS, Dr. Solin stressed. The tool "will help physicians understand the underlying biology of [DCIS] for the individual patient, accurately gauging the risk for that patient and helping guide treatment," he said. Clinical and pathologic factors are not reliable enough on their own to determine whether radiation following breast-conservation surgery will confer any survival benefit, he explained.
Genomic Health has announced the Oncotype DX DCIS tool will be available by the end of December 2011. In response to questions about the price of the test and insurance coverage, Dr. Solin noted that, in aggregate, the savings associated with avoiding unnecessary additional treatment in patients with a low-risk DCIS score would more than compensate for the price of the test in individual patients.
Dr. Solin reported having no relevant financial disclosures. The study team included employees of Genomic Health.