Characterization of BCL-XL, MCL-1, and BAX Protein Expression in Response to Neoadjuvant Chemotherapy in Breast Cancer

Abstract

The use of chemotherapy has improved the overall treatment of breast cancer, which is frequently administered in the form of neoadjuvant chemotherapy (NAC). Apoptosis is an established cell stress response to NAC in preclinical models; however, there is limited understanding of its role in clinical cancer, specifically, its contribution to favorable pathologic responses in breast cancer therapy. Here, we aimed to characterize the change in protein expression of 3 apoptosis-associated biomarkers, namely, BCL-XL, MCL-1, and BAX in breast cancer in response to NAC. For this, we utilized a set of 68 matched invasive breast cancer FFPE samples that were collected before (pre) and after (post) the exposure to NAC therapy that were characterized by incomplete pathologic response. Immunohistochemistry (IHC) analysis suggested that most of the samples show a decrease in the protein expression of all 3 markers following exposure to NAC as 90%, 69%, and 76% of the matched samples exhibited a decrease in expression for BCL-XL, MCL-1, and BAX, respectively. The median H-score of BCL-XL post-NAC was 150/300 compared with 225/300 pre-NAC (P value <0.0001). The median H-score of MCL-1 declined from 200 pre-NAC to 160 post-NAC (P value <0.0001). The median H-score of BAX protein expression decreased from 260 pre-NAC to 190 post-NAC (P value <0.0001). There was no statistically significant association between the expression of these markers and stage, grade, and hormone receptor profiling (luminal status). Collectively, our data indicate that the expression of apoptosis regulatory proteins changes following exposure to NAC in breast cancer tissue, developing a partial pathologic response.