Clinical Utility of Oncotype DX Testing in Synchronous Bilateral and Unilateral Multifocal Breast Cancer.

[PURPOSE] We investigated the prevalence, clinicopathological correlates, and therapeutic implications of Oncotype DX recurrence score (RS) differences between synchronous tumors in bilateral and unilateral multifocal breast cancer.

[METHODS] Patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer who underwent Oncotype DX testing of at least two synchronous tumor foci at a tertiary center between 2015 and 2023 were retrospectively identified. Recurrence score risk-category discordance was defined according to cutoffs from the TAILORx and RxPONDER trials. Multivariable linear regression was used to identify the clinicopathological factors associated with absolute differences in RS. Disease-free survival was estimated by using the Kaplan-Meier method and compared using the log-rank test.

[RESULTS] Among 131 patients (38 bilateral, 93 unilateral multifocal), RS risk-category discordance occurred in 21 and 24.7%, respectively, leading to chemotherapy escalation in half of the discordant cases. In bilateral disease, only the progesterone receptor score difference was significantly associated with the absolute RS difference (β = 1.95; 95% confidence interval [CI], 0.44-3.46; P = 0.013). In unilateral disease, absolute RS difference was independently associated with differences in HER2, progesterone receptor, and estrogen receptor scores (all P < 0.05). Recurrence score correlation between paired tumors was higher in unilateral multifocal than in bilateral disease (r = 0.66 vs. 0.36). Disease-free survival showed a consistent, although nonsignificant, trend toward poorer outcomes in discordant cases across both cohorts.

[CONCLUSIONS] Recurrence score risk-category discordance is frequent in synchronous bilateral and unilateral multifocal breast cancer and often changes adjuvant chemotherapy recommendations. Reliance on single-lesion testing risks missing clinically relevant genomic heterogeneity. Multilesion testing may be warranted in selected patients to optimize treatment selection.