Results of the 70-gene signature assay strongly influence physician's treatment recomendations for patients with early breast cancer who were classified as intermediate risk by the 21-gene assay.
The 70-gene signature assay (70-GS) provides clinically actionable information, and the results may be associated with adjuvant therapy decisions, according to a new study published in JAMA Oncology.
The 70-GS is a molecular diagnostic assay that provides binary classification for patients with early-stage breast cancer. The assay identifies genes often correlated with disease outcome in systematically untreated patients, and classifies them as either low or high risk.
The assay provides this information for patients classified as intermediate risk by the 21-gene assay (21-GA), which was developed by selecting genes associated with recurrence-free survival in patients with estrogen receptor (ER)—positive, human epidermal growth factor receptor 2 (HER-2)–negative findings who received 5 years of tamofixen therapy.
“The 21-GA gives an intermediate result for 39% to 69% of patients undergoing testing, leaving many physicians and patients without definitive treatment guidance,” wrote the authors.
The PROMIS trial included 840 patients with breast cancer and an intermediate 21-GA result in from May 20, 2012 to December 31, 2015. RNA samples were extracted from formalin-fixed, paraffin-embedded breast tumor specimens for the 70-GS assay, which provides a numerical index ranging from -1.000 to 1.000, and a dichotomous categorization of low risk or high risk depending on whether the index was greater than 0 (low risk), 0, or less (high risk). Patients’ tumor indexes were calculated by comparing them to known low- and high-risk tumor profiles.
Authors also analyzed overall treatment change, which was derived from the percentage of patients with a change from their baseline treatment recommendation after receiving their 70-GS results.
Based on the 21-GA results, 382 patients (45.5%) were recommended to receive adjuvant chemotherapy (CT), and 458 (54.5%) were recommended not to receive CT as part of their adjuvant treatment regimen. Recommendations for CT were more common for patients with an RS above 26 and less frequent for patients with an RS below 21.
The 70-GS reclassified the patients: 374 were classified as being low risk and 466 as high risk. Results showed that the 70-GS classifications were linked to significant changes in CT treatment decisions on whether to add or forgo CT. Following the results of the 70-GS, physicians felt more confident in their treatment recommendations in 78.6% of cases, and felt less confident in 5.8% of the cases.
Overall, the trial saw that treatment recommendations based on the 70-GS or 21-GA were often conflicting, and 75.8% of patients changed their treatment regimen. The additional information provided by the 70-GS results caused physicians to change their adjuvant therapy recommendation for 33.6% of all patients. In addition, physicians followed the adjuvant therapy recommendation from the 70-GS for 89% of patients.
“The high proportions of cases in which physicians changed their treatment regimens by adding or removing CT, along with a self-reported increase in confidence substantiates the influence of the 70-GS when used for adjuvant decision making,” concluded the authors.