Background: Although an advantage of neoadjuvant chemotherapy (NAC) is eradication of axillary disease, nodal pCR rates are much lower for ER+/HER2− breast cancer than other subtypes. We sought to evaluate the association of genomic risk with nodal pCR in ER+/HER2− disease. Methods: Patients with ER+/HER2− clinically-node-positive (cT0-cT4d/cN1-cN3/cM0) breast cancer treated with NAC and surgery 2010–2018 in the National Cancer Database were identified. Low genomic risk was classified as Oncotype Dx Recurrence Score (RS) 0–25, or Mammaprint 70-gene or RS coded as “Low.” High genomic risk included RS >25, or 70-gene or RS coded as “High.” Nodal pCR was compared between patients with high versus low genomic risk by using chi-square tests and multivariable logistic regression. Results: Of 15,698 patients, genomic risk was available for 692 of 15,698 (4.4%). High genomic risk was similar between patients aged <50 years versus 50+ (50.8% vs. 57.3%, p = 0.10). Nodal pCR was higher in high genomic risk (25.0%) than low genomic risk (10.4%, p < 0.001). This difference was observed both for patients aged <50 years (29.9% vs. 9.8%) and aged ≥50 years (22.7% vs. 10.8%). On multivariable analysis adjusted for potential confounding variables, including age, grade, and PR status, genomic risk was independently associated with decreased odds of residual nodal disease (odds ratio 0.49, p = 0.002). Conclusions: For patients with node-positive ER+/HER2− breast cancer treated with NAC, nodal pCR was highest in patients aged <50 years with high genomic risk tumors. In contrast, nodal pCR rates were low in patients with low genomic risk tumors, regardless of age. This information may help when counseling patients regarding axillary management.
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