Real-world use of multigene signatures in early breast cancer: differences to clinical trials

Abstract

Purpose In Italy, Lombardy was the first region to reimburse multigene assays (MGAs) for patients otherwise candidates for chemotherapy. This is a real-world experience of MGAs usage in six referral cancer centers in Lombardy. Methods Among MGAs, Oncotype DX (RS) was used in 97% of cases. Consecutive patients tested with Oncotype DX from July 2020 to July 2022 were selected. The distribution of clinicopathologic features by RS groups (low RS: 0–25, high RS: 26–100) was assessed using chi-square and compared with those of the TAILORx and RxPONDER trials. Results Out of 1,098 patients identified, 73% had low RS. Grade and Ki67 were associated with RS (p < 0.001). In patients with both G3 and Ki67 > 30%, 39% had low RS, while in patients with both G1 and Ki67 < 20%, 7% had high RS. The proportion of low RS in node-positive patients was similar to that in RxPONDER (82% vs 83%), while node-negative patients with low RS were significantly less than in TAILORx (66% vs 86%, p < 0.001). The distribution of Grade was different from registration trials, with more G3 and fewer G1 (38% and 3%) than in TAILORx (18% and 27%) and RxPONDER (10% and 24%) (p < 0.001). Patients ≤ 50 years were overrepresented in this series (41%) than in TAILORx and RxPONDER (31% and 24%, respectively) (p < 0.001) and, among them, 42% were node positive. Conclusions In this real-world series, Oncotype DX was the test almost exclusively used. Despite reimbursement being linked to pre-test chemotherapy recommendation, almost 3/4 patients resulted in the low-RS group. The significant proportion of node-positive patients ≤ 50 years tested indicates that oncologists considered Oncotype DX informative also in this population.

The Evolving Role of Genomic Testing in Early Breast Cancer: Implications for Diagnosis, Prognosis, and Therapy

“…Multigene genomic assays are RNA-based molecular tests that assist treatment decision-making in early breast cancer (EBC) coupled with clinicopathological parameters [ 1 , 2 , 3 ]. Although assessing the standard variables (e.g., age, menopausal status, tumor size, lymph node status, histological grade, lymph vascular invasion, hormone receptor (HR), HER2, and Ki67 labeling index) can be highly informative for many patients, ~15% of women with stage I–III hormone receptor-positive (HR+) disease will go through metastatic events [ 4 ].…”