Abstract

Neoadjuvant chemotherapy (NAC) is standard for most triple-negative and human epidermal growth factor receptor 2 (HER2)+ breast cancers, and frequently downstages node-positive (cN+) disease, permitting omission of axillary dissection. In estrogen receptor (ER)+/HER2- disease, response rates are lower. Whether Ki67 is associated with axillary downstaging in ER+/HER2- diseaseis unknown. With institutional review board approval, we queried our institutional database to identify all patients with primary ER+/HER2- biopsy-proven cN+ breast cancer treated with NAC followed by surgery from January 2012 to December 2021. Nodal pathologic complete response (pCR) rates were evaluated by pretreatment Ki67 and patient age. 315 patients (median age 50years) were included. Nodal pCR rate was 24.8% (78/315) and was higher in patients aged < 50years than ≥ 50years (31.8% versus 17.7%, p = 0.004). Ki67 was available on 236 patients (74.9%). Median Ki67 was 29.0% (range 1-98%) and did not differ by age category (p = 0.23). Patients with nodal pCR had higher Ki67 (median 40.3% versus 25.0%, p < 0.001). Nodal pCR rates were 28.4% (Ki67 ≥ 20%) versus 8.1% (Ki67 < 20%) (p < 0.001). On multivariable analysis, Ki67 and age category were predictive of nodal pCR. Combining these two parameters together, nodal pCR rates in age < 50years were 35.8% when Ki67 ≥ 20% versus 14.3% with Ki67 < 20% (p = 0.02). In contrast, for age ≥ 50years, nodal pCR was 21.0% for Ki67 ≥ 20% versus 2.6% with Ki67 < 20% (p = 0.008). In ER+/HER2- breast cancer, nodal downstaging with NAC is associated with age (< 50years) and Ki67 (≥ 20%). Age and Ki67 should be considered for NAC decision-making and can identify patients with high rates of nodal downstaging (36%) who would benefit from NAC to enable axillary preservation.

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