Can Multigene Testing Provide Additional Risk Stratification for Patients Considered Eligible for Accelerated Partial Breast Irradiation?

Abstract

PURPOSE/OBJECTIVE(S)\nFollowing breast conserving surgery, the risk of ipsilateral in-breast recurrence is equivalent between whole breast radiation therapy (WBRT) and accelerated partial breast irradiation (APBI) in patients with low-risk tumors according to ASTRO guidelines. The Oncotype DX Recurrence Score (RS) is prognostic for both local and distant recurrence in ER+/HER2- breast cancer. Whether the RS can identify patients at increased risk for local recurrence among those considered eligible for APBI is unclear.\n\n\nMATERIALS/METHODS\nWe retrospectively identified consecutive patients with clinical T1-2, ER+/HER2-, node-negative tumors with an available RS, and who were treated with APBI from 2010-2019 at a single institution. RS testing was performed for all patients with ER+/HER2-, invasive cancers ≥ 0.5 cm who were candidates for chemotherapy. Patients were considered for APBI based on the 2009 ASTRO guidelines. Characteristics were compared between patients with RS ≤ 25 and RS > 25 using Fisher s exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. The 6-year cumulative incidence rate (CIR) of local recurrence was estimated using Kaplan-Meier methods and was compared between groups using the log-rank test.\n\n\nRESULTS\n223 patients were identified; the median (IQR) age was 63 years (57-68) and median (IQR) tumor size was 1.0 cm (0.8-1.4). 201 patients (90%) had RS ≤ 25 and 22 patients (10%) had RS > 25. Nine patients aged ≤ 50 years were included, all of whom had RS ≤ 25. Compared with the RS ≤ 25 group, patients with RS > 25 more frequently had tumors that were progesterone receptor negative (55% vs. 9%; P < 0.001), grade III (50% vs. 11%; P < 0.001) and were more likely to have received chemotherapy (73% vs. 5%; P < 0.001). Uptake of endocrine therapy was similar in the RS ≤ 25 group compared with RS > 25 group (97% vs. 95%; P\u202f=\u202f0.39), as was median (IQR) duration of endocrine therapy at 3 years (2-5) for both groups (P\u202f=\u202f0.9). The median (range) follow-up was 3.6 years (0.1-10.2) and was similar between groups (P\u202f=\u202f0.64). Overall, 4 ipsilateral in-breast recurrences occurred during follow-up, with 2 events (1.0%) in the RS ≤ 25 group and 2 events (9.1%) in the RS > 25 group (P\u202f=\u202f0.05). The 6-year CIR of local recurrence was higher among patients with RS > 25 compared with RS ≤ 25 (6-year CIR [95% CI] 0.01 [0-0.04] vs. 0.08 [0-0.21]; P\u202f=\u202f0.006). Due to a low number of events, a multivariable analysis of factors associated with local recurrence could not be performed.\n\n\nCONCLUSION\nThe overall risk of local recurrence following APBI in patients with early-stage, ER+ tumors is low, but our findings suggest that the RS may identify patients at increased risk for local failure among a favorable risk population. Prospective studies are needed to assess whether genomic profiling can be used for additional risk stratification for patients considered eligible for APBI, to identify patients for whom de-escalation of WBRT may not be advisable.