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

Background: Breast conservation therapy for patients with DCIS includes breast conserving surgery (BCS) with post-operative 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.

Methods: 7-gene biosignature was evaluated in women diagnosed with DCIS between 2019-2022. 7-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 DCISionRT on RT recommendations was assessed using McNemar's test. The 7-gene biosignature decision score (DS) was compared between treatment types by t-test.

Results: 101 patients underwent BCS for DCIS. Of those, 24 (24%) met RTOG 9804 criteria and 45 (45%) had nuclear grade 3 DCIS. Prior to 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) versus those who received RT (DS median 3.7) (p<0.0001). There were 22 of 39 patients (56%) with DS<2 and 11 of 40 patients (28%) with DS 2-4 who were not treated with RT. More patients with DS>4 (20/22, 91%) were treated with RT than DS<2, p<0.001, and patients with DS>4 were treated with an increased RT dose, p=.028.

Conclusions: 7-gene biosignature test resulted in a 35% reduction in patients treated with adjuvant RT. Patients with higher decision scores were more likely to receive RT and to receive a greater RT dose.