Neoadjuvant Chemotherapy and Nodal Response Rates in Luminal Breast Cancer: Effects of Age and Tumor Ki67

Abstract

Background: 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- disease is unknown.

Methods: 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.

Results: 315 patients (median age 50 years) were included. Nodal pCR rate was 24.8% (78/315) and was higher in patients aged < 50 years than ≥ 50 years (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 < 50 years were 35.8% when Ki67 ≥ 20% versus 14.3% with Ki67 < 20% (p = 0.02). In contrast, for age ≥ 50 years, nodal pCR was 21.0% for Ki67 ≥ 20% versus 2.6% with Ki67 < 20% (p = 0.008).

Conclusions: In ER+/HER2- breast cancer, nodal downstaging with NAC is associated with age (< 50 years) 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.

FIG. 1

a Percent of patients with ER+/HER2− breast cancer with nodal, breast, and total pCR after neoadjuvant chemotherapy. b Percent with nodal, breast, and total pCR by age category. c Percent with nodal, breast, and total pCR by Ki67 < 20% versus ≥ 20%

FIG. 2

Histograms showing the distribution of Ki67 by age group

FIG. 3

Percent with nodal, breast, and total pCR by age category and pre-NAC Ki67

FIG. 4

Percent undergoing SLN surgery only by combinations of age category and pre-NAC Ki67 category during the period 2017–2021 and excluding patients with inflammatory breast cancer