Effect of neoadjuvant therapy on breast cancer biomarker profile

Breast cancer clinical management requires the assessment of hormone receptors (estrogen (ER) and progesterone receptor (PR)), human epidermal growth factor receptor 2 (HER2) and cellular proliferation index Ki67, by immunohistochemistry (IHC), in order to choose and guide therapy according to tumor biology. Many studies have reported contradictory results regarding changes in the biomarker profile after neoadjuvant therapy (NAT). Given its clinical implications for the disease management, we aimed to analyze changes in ER, PR, HER2, and Ki67 expression in paired core-needle biopsies and surgical samples in breast cancer patients that had either been treated or not with NAT.

We included 139 patients with confirmed diagnosis of invasive ductal breast carcinoma from the Colombian National Cancer Institute. Variation in biomarker profile were assessed according to NAT administration (NAT and no-NAT treated cases) and NAT scheme (hormonal, cytotoxic, cytotoxic + trastuzumab, combined). Chi-squared and Wilcoxon signed-rank test were used to identify changes in biomarker status and percentage expression, respectively, in the corresponding groups.

We did not find any significant variations in biomarker status or expression values in the no-NAT group. In cases previously treated with NAT, we did find a statistically significant decrease in Ki67 (p < 0.001) and PR (p = 0.02605) expression. When changes were evaluated according to NAT scheme, we found a significant decrease in both Ki67 status (p = 0.02977) and its expression values (p < 0.001) in cases that received the cytotoxic treatment.

Our results suggest that PR and Ki67 expression can be altered by NAT administration, whereas cases not previously treated with NAT do not present IHC biomarker profile variations. The re-evaluation of these two biomarkers after NAT could provide valuable information regarding treatment response and prognosis for breast cancer patients.