Impact of anthracyclines in genomic high-risk, node-negative, HR-positive/HER2-negative breast cancer

The benefit of anthracyclines for patients with high 21-gene recurrence score (RS) is unclear, despite the widespread use of RS to guide adjuvant chemotherapy treatment for hormone receptor (HR)-positive /human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This study aimed to assess whether patients with RS ≥ 31 would have improved outcomes with the addition of anthracyclines to taxane-based chemotherapy.

We included patients from TAILORx with RS ≥ 11 who received treatment with either taxanes with cyclophosphamide (TC) or taxane with anthracyclines/cyclophosphamide (T-AC). Distant recurrence-free interval (DRFI), distant recurrence-free survival (DRFS), and overall survival (OS) were compared, controlling for age, tumor size and grade, receptor status, and RS. Spline regression was used to estimate adjusted hazard ratio (aHR) for receipt of T-AC (versus TC) for these endpoints as a function of RS.

A total of 2549 patients who received either T-AC or TC were included in the primary analysis. In patients with RS ≥ 31, receipt of T-AC was associated with improved DRFI (5-year rate of 96.1% with T-AC versus 91.0% with TC, aHR 0.31, P = 0.006), DRFS (95.4% versus 89.8%, aHR 0.49, P = 0.032), and a trend toward improved OS (adjusted 5-year rate 97.3% versus 93.6%, aHR 0.67, P = 0.31). Spline regression demonstrated increasing anthracycline benefit with increasing RS.

Patients with early-stage, HR-positive/HER2-negative breast cancer with the highest genomic risk disease (RS ≥ 31) may benefit from the addition of an anthracycline to taxane-based adjuvant chemotherapy. Genomic RS testing may predict anthracycline benefit more accurately than clinicopathological factors such as nodal status.