Relevance of the 21-gene expression assay in male breast cancer: A systematic review and meta-analysis

Introduction: The 21-gene assay provides prognostication for estrogen receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) early female breast cancer patients. This signature has not been validated in male breast cancer (MBC). Methods: A systematic review and meta-analysis was performed in accordance to the PRISMA guidelines. Retrospective cohort studies comparing 21-gene assay scores in female and MBC were included. Dichotomous variables were pooled as odds ratios (OR) and associated 95% confidence intervals (CI) using the Mantel–Haenszel method. Results: Six studies including 176,338 patients were included (mean age of 63.4 years, range: 33–88). Of these, 1.0% had MBC (1826/176,338) and 99.0% were female patients (174,512/176,338). MBC patients were more likely to have increased tumour stage, nodal involvement, and grade 3 disease (all P < 0.001) In MBC patients, the mean score was 18.8 (range: 11–26) vs. 13.4 (range 0–33) in female patients (P < 0.001). In MBC patients, 22.4% had scores >30 (408/1822) versus 18.3% in female patients (31,852/174,500). In female patients, 52.0% had scores <18 (90,787/174,500) versus 47.8% in MBC (471/1822). Overall, patients with female patients were as likely to have scores <18 (OR: 1.04, 95% CI: 0.94–1.16), scores 18–30 (OR: 1.12, 95% CI: 1.00–1.26) and scores >30 (OR: 0.69, 95% CI: 0.45–1.07) as MBC patients. Conclusion: There are similar anticipated scores for female and MBC undergoing 21-gene expression assay testing for early stage, ER+/HER2-breast cancer. In the absence of stage matching, cautious interpretation of these results is required. Validation of the 21-gene assay in MBC is still required.