21-Gene Recurrence Score Adds Significant Value for Grade 3 Breast Cancers: Results From a National Cohort

The 21-gene recurrence score (RS) is used to identify patients with hormone receptor-positive early-stage breast cancer who may benefit from the addition of chemotherapy to endocrine therapy. We hypothesized that many women with poor prognostic histopathologic grade 3 disease may be offered chemotherapy irrespective of RS results, of whom a subset may not benefit from adjuvant chemotherapy.

A total of 30,864 women in the National Cancer Database were diagnosed with pT1c to pT2, pN0 to pN1, grade 3 estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive breast carcinoma from 2010 to 2015. RS was stratified as low (less than 18), intermediate (18 to 30), and high (31 or more). Overall survival by RS was evaluated by Kaplan-Meier, log-rank, and multivariable proportional hazards, with adjustment for relevant clinical and demographic variables.

RS testing in grade 3 cancers increased between 2010 and 2015 (pN0, 53% to 72%; pN1, 16% to 36%). Among the 13,558 women with pN0 and the 2,840 with pN1 disease with RS testing, 27.1% and 30.0%, respectively, had low scores (less than 18). The 5-year overall survival rate for patients with a high RS, but not low RS, was significantly higher with chemotherapy (v no chemotherapy; absolute differences: high RS pN0 = 12.2% and pN1 = 25.5%, both P < .001; low RS pN0 = 2.5%, P = .07; and pN1 = 1.0%, P = .27), findings that were reinforced in multivariable analyses risk adjusted by clinicopathologic characteristics.

Increased use of RS may help to better tailor treatment recommendations by stratifying patients with grade 3 disease into those who will and will not derive survival benefit and should be considered in all patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative T1c to T2, N0 to N1 disease.