Genomic risk classification by the 70-gene signature and 21-gene assay in African American early-stage breast cancer patients.
Authors: Robinson Patricia A. , Tsai Michaela L. , Lo Shelly S. , Lee June , Socoteanu Matei P. , Kling Heather , Bolner Michelle , Blumencranz Lisa Eileen , Audeh William 
Published: June 2021

e12568 Background: Genomic risk of recurrence assays provide prognostic information that aids treatment recommendations for patients with early breast cancer (EBC). The 70-gene signature (MammaPrint/MP) and the 21-gene assay (Oncotype DX/ODX) were both validated by large prospective, randomized clinical trials. Previous studies have directly compared the performance of these assays, with moderate discordance widely observed. Recent work showed poor prognostic performance of the ODX in African American (AA) EBC patients (Hoskins et al., 2021). Here, we compare the concordance of two genomic tests in an AA cohort. Methods: This retrospective analysis included a subset of self-reported AA patients from the prospective, observational PROMIS (n = 66, NCT01617954) and FLEX (n = 29, NCT03053193) registry trials, for whom both MP and ODX RS results were available. Patients were enrolled from 2012 to present. The PROMIS trial enrolled patients with intermediate ODX RS (18-30). MP results were obtained from standard testing performed centrally by Agendia, Inc. (Irvine, CA); ODX testing was performed by Genomic Health, Inc. (Redwood City, CA) and results were collected from patient case report forms. Results: AA patients (n = 95) included in this sub-analysis were 77% post-menopausal with a median age of 60 years. 28% of patients were aged ≤ 50 years. Of patients with metabolic data (n = 49), 63% were obese by body mass index (BMI > 30), and 23% had type 2 diabetes mellitus (T2DM). Tumors were predominantly invasive ductal carcinoma (82%), T1 (73%), grade 2 (53%), ER+ (99%), HER2-negative (94%), lymph node-negative (86%), and MP High Risk (66%). By ODX clinical RS, 17% of tumors classified as low (0-17), 80% intermediate (18-30), and 3% high (31-100) risk. As expected, the large intermediate RS group reflects the inclusion of PROMIS patients. By TAILORx RS ranges, 76% of tumors were low risk (≤25). Of these, 61% (n = 44/72) classified as MP High Risk. Notably, 62% (n = 41/66) of tumors with TAILORx intermediate RS (11-25) were MP High Risk. Conclusions: The overall discordance between MP and ODX was 51% in these AA patients. Discordance was more frequent (61%) in ODX low risk (RS≤25) cases. Notably, of tumors with TAILORx intermediate RS (11-25), the majority (62%) classified as MP High Risk. Combined with previously published data in AA patients (Nunes et al., 2016), this results in a total of 57% (n = 52/91) of ODX low RS (≤25) tumors classified as MP High Risk. Recent data indicate that AA patients who receive a low (≤10 or ≤25) or intermediate RS (11-25) have higher recurrence rates and lower survival than White/Caucasian EBC patients with the same RS. In the current study, clinical outcomes are forthcoming; however, these data suggest the majority of AA patients are more likely to receive a MP High Risk result, which may capture the diversity of pathways driving tumor metastasis. Clinical trial information: NCT01617954, NCT03053193.