Genomic profiling of primary tumor and lymph node metastasis in patients with clinically node-positive breast cancer: prospective cohort study within TAXIS (OPBC-03, SAKK 23/16, IBCSG 57–18, ABCSG-53, GBG 101)

INTRODUCTION: Genomic tests informing systemic therapy recommendations for breast cancer (BC) were developed and validated on primary tumor (PT) tissue. Agreement of genomic tests between the PT and matched lymph node metastases (LNm) in patients with BC is currently unclear, which limits their use in nodal tissue. METHODS: Prespecified study within the international phase III TAXIS trial (NCT03513614). Tissue from PT and matched LNm were assessed with the primary objective of comparing genomic recurrence risk and subtypes. Clinical risk was assessed using the Adjuvant!Online tool and clinical subtypes were determined based on hormone receptor and Her2 testing. Agreement was assessed using Cohen's Kappa (Κ). RESULTS: Eighty-nine patients with stage II/III BC from 26 European centers were included. Median age was 63 years (range 50-72). Agreement in genomic risk between the PT and LNm was found in 84.3 % (Κ=0.64). However, 15.6 % exhibited genomic high risk in the LNm and low risk in the PT, while 16.0 % demonstrated low risk in the LNm and high risk in the PT. Genomic subtypes of PT and LNm showed disagreement in 17.1 % of patients with luminal BC (Κ=0.70). 96.5 % of patients were clinically categorized as high risk, whereas genomically, 25.6 % of them were classified as low risk in the LNm (Κ=0.17) and 31.7 % in the PT (Κ=0.13). Genomic subtyping reclassified 35.5 % of the clinically luminal tumor subtypes. CONCLUSION: Disagreement in genomically estimated risk exists in over 15 % of patients, potentially leading to over- or undertreatment. Consequently, the applicability of genomic tests in LNm remains controversial.