To investigate the concordance of biomarkers in the primary tumors and axillary lymph nodes of HER2-positive early breast cancer, the effect of neoadjuvant therapy on biomarkers, and the prognostic value of biomarkers.

The pathological and clinical data of 128 patients with HER2-positive breast cancer who underwent neoadjuvant therapy at the Breast Oncology Department of the Fifth Medical Center of the PLA General Hospital from April 2013 to April 2019 were retrospectively analyzed. The concordance of the expression levels of estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 in the primary breast tumors and matched axillary lymph node metastases of HER2-positive early breast cancer, the changes in the status of ER, PR, HER2, and Ki67 before and after neoadjuvant therapy, and their prognostic value were investigated. SPSS 20.0 was used for statistical analyses. Differences between groups and before and after treatment were compared by t or χ² test, and the Kaplan-Meier curve was used to analyze the event free survival (EFS) of patients.

The rates of discordance in ER and RP between primary breast tumors and corresponding lymph node metastases were 5.5% and 7.3%, respectively, and the Kappa values were 0.886 and 0.824, respectively. The mean Ki67 indexes of primary breast tumors and lymph node metastases were 43.0%±20.0% and 42.5%±19.5%, respectively; there was no differences in mean Ki67 index (t=0.24, P=0.811) or the proportion patients with Ki67 index over 30% (61.8% vs 63.6%, P=1.000) between primary breast tumors and lymph node metastases. There was no statistically difference in the pathological complete response (pCR) rate between patients with consistent and inconsistent statuses of ER/PR/HER2 (52.2% vs 55.6%, P=1.000). Forty-three patients had both pre-neoadjuvant core-needle biopsy and post-neoadjuvant immunohistochemical results. There was no change in ER status. Changes from positive to negative status for PR were observed in nine cases, and gain of PR status occurred in 1 case (P=0.021). The negative conversion of PR status had no influence on EFS when compared with patients who had sustained positive expression (HR=1.34, 95%CI: 0.19-9.80, P=0.766). Fifteen patients (34.9%) had loss of HER2 expression following neoadjuvant treatment. There was no difference between patients with and those without change in HER2 status in terms of EFS (HR=0.76, 95%CI: 0.21-2.80, P=0.692). We observed a significant decrease in Ki67 index after neoadjuvant treatment: The median Ki-67 index before and after neoadjuvant treatment was 35% vs 25% (P=0.001). After treatment, the 5-year EFS rate was higher in patients with Ki67 reduction than in those with no reduction; although the difference was not statistically significant, it was clinically significant (5-year EFS rate was 80.9% vs 71.4%, HR=0.49, 95%CI: 0.12-1.71, P=0.261).

The expression statuses of ER, PR, HER2 and Ki67 are in high degree of concordance between primary tumors and matched lymph node metastases in HER2-positive breast cancer. After neoadjuvant therapy, the ER status of patients remains unchanged, and the negative conversion of PR and HER2 status has no significant effect on the prognosis. Ki67 index decreases significantly after neoadjuvant treatment, which may predict a better prognosis.