To determine the effect of the 21-gene recurrence score (RS) on outcome and chemotherapy decision in breast invasive lobular carcinoma (ILC).

We included 6467 patients with early stage and estrogen receptor-positive ILC from the Surveillance, epidemiology, and end results database.

A total of 9.1, 31.4, and 70.1% of patients with low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. A higher RS was independently associated with poor breast cancer-specific survival, and receipt of chemotherapy was not related to better breast cancer-specific survival in low-, intermediate-, or high-risk RS groups.

The 21-gene RS could impact chemotherapy decision making in early-stage ILC. However, adjuvant chemotherapy does not appear to improve outcome in high-risk RS cohort.