Utility of 21-Gene Recurrence Score in Male Breast Cancer

Recurrence score (RS) is a 21-gene analysis (Oncotype DX) that assesses risk of breast cancer recurrence and benefit from chemotherapy. While extensively validated in female patients, RS has not been well studied in male patients.

Using the National Cancer Database (NCDB) we identified patients with pT1-2, N0-1 estrogen receptor (ER)+ human epidermal growth factor (HER)2- breast cancer (2010-2023) to assess RS usage and prognostic implications. Groups were compared using chi-squared tests. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression.

We identified 9908 male and 1,111,898 female patients. While overall rate of RS testing was lower in male (42%) than female (46%) patients, RS use increased markedly between 2010 and 2023 (18-66% in male and 28-62% in female patients), and in 2023, the rate was slightly higher for male patients (p = 0.04). Among those tested, male patients were more likely to have RS ≥ 26 (19% versus 14%, p < 0.001). From 2019 to 2023, chemotherapy use in patients with RS ≥ 26 was lower in male than female patients (68% versus 77%, p < 0.001). Male patients with RS ≥ 26 had significantly poorer OS if chemotherapy was omitted (aHR 1.5, p = 0.03), with a larger difference for male patients aged < 65 years (82% versus 93% 5-year OS without versus with chemotherapy, p = 0.009) than for male patients ≥ 65 years (75% versus 84%, respectively, p = 0.28).

RS testing increased between 2010 and 2023 for both sexes, and RS influenced receipt of chemotherapy. Male patients had higher RS but were less likely to receive chemotherapy when RS ≥ 26, and when chemotherapy was omitted, they had worse OS, revealing the importance of chemotherapy among males with high RS.