First versus second-generation molecular profiling tests: How both can guide decision-making in early-stage hormone-receptor positive breast cancers?

Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) tumors represent the most common types of early-stage breast cancer. However, their response to adjuvant systemic treatments varies widely due to tumor heterogeneity. Current decisions for adjuvant treatment rely heavily on clinical and pathological characteristics, which can sometimes lead to overtreatment. Accurately identifying patients who will benefit from adjuvant chemotherapy at an individual level remains a challenge. Multigene profiling assays are now widely used in clinics to better assess recurrence risk and chemotherapy response for HR+ disease. In this report, we examine the advantages and limitations of two widely used molecular profiling tests—Oncotype DX and Prosigna. Both Oncotype DX and Prosigna have been demonstrated to be effective prognostic tools in early breast cancer, with Oncotype DX also being validated as a predictive tool to guide chemotherapy decisions. We focus on studies that directly compare these molecular tests and discuss how their strengths can be leveraged to improve clinical decision-making for early-stage HR+ breast cancers. Finally, we highlight remaining knowledge gaps and propose directions for future research.