Impact of a 7-Gene Predictive Biosignature on Adjuvant Radiation Therapy Recommendations in Patients Undergoing Breast-Conserving Surgery for Ductal Carcinoma In Situ.

Abstract

Breast conservation therapy for patients with ductal carcinoma in situ (DCIS) includes breast-conserving surgery (BCS) with postoperative radiotherapy (RT). Because RT does not impact overall survival, identifying women who do not benefit from RT would allow de-escalation of therapy. We evaluated the impact of a novel 7-gene DCIS biosignature on adjuvant radiation recommendations for patients undergoing BCS for DCIS. Seven-gene biosignature was evaluated in women diagnosed with DCIS between 2019 and 2022. Seven-gene biosignature is reported as a "decision score" (DS) and categorical risk groups. RT recommendation before and after 7-gene biosignature was identified through retrospective chart review after IRB approval. The impact of the DS on RT recommendations was assessed using McNemar's test. The 7-gene biosignature DS was compared between treatment types by t -test. A total of 101 patients underwent BCS for DCIS. Of those, 24 (24%) met Radiation Therapy Oncology Group 9804 criteria and 45 (45%) had nuclear grade 3 DCIS. Before 7-gene biosignature testing, all 101 patients were recommended RT; after testing, 35 patients omitted RT, corresponding to a 35% decision change (p < 0.0001). Patients who ultimately omitted radiation had a significantly lower decision score (DS median 0.9) vs those who received RT (DS median 3.7; p < 0.0001). There were 22 of 39 patients (56%) with DS lower than 2 and 11 of 40 patients (28%) with DS 2 to 4 who were not treated with RT. More patients with DS higher than 4 (20 of 22, 91%) were treated with RT than DS lower than 2 (p < 0.001), and patients with DS higher than 4 were treated with an increased RT dose (p = 0.028). The 7-gene biosignature test resulted in a 35% reduction in patients treated with adjuvant RT. Patients with higher DSs were more likely to receive RT and to receive a greater RT dose.