Histomorphological Factors Predicting the Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Abstract

Purpose: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy.

Methods: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled. The core needle biopsy specimens acquired before NAC were used to analyze the clinicopathologic variables and overall performance of the predictive model for therapeutic response.

Results: Independent predictors of pathologic complete response after NAC were found to be higher number of tumor infiltrating lymphocytes (p=0.007), absence of clear cytoplasm (p=0.008), low necrosis (p=0.018), and high histologic grade (p=0.039). In the receiver operating characteristics curve analysis, the area under curve for the combination of these four variables was 0.777.

Conclusion: The present study demonstrated that a predictive model using the above four variables can predict therapeutic response to single-regimen NAC with the combination of doxorubicin, cyclophosphamide, and docetaxel in TNBC. Therefore, adding these morphologic variables to clinical and genomic signatures might enhance the ability to predict the therapeutic response to NAC in TNBC.

Keywords: Core needle biopsy; Neoadjuvant therapy; Treatment outcome; Triple-negative breast neoplasms.

Figure 1. Representative microphotographs of tumor infiltrating lymphocytes (TIL) according to TIL grade (H&E stain, ×200). (A) None; almost no lymphocytes are present. (B) Mild; only a few lymphocytes infiltrate the tumor stroma. (C) Moderate; moderate lymphocytic infiltration in the stroma. (D) Severe; dense infiltration of lymphocytes surrounding the tumor nests.

Figure 2. Representative histopathologic parameters. (A) Peritumoral tumor infiltrating lymphocytes (TIL); the lymphocytes surrounding the peripheral tumor border. The border between the tumor nests and the inner stroma is demarcated by the black line, and lymphocytes in the stroma surrounded by the line are considered to be stromal TIL (H&E stain, ×200). (B) The left half of the core biopsy specimen is totally necrotized. Diffuse necrosis (H&E stain, ×100). (C) Tumor cells with clear cytoplasm (H&E stain, ×400).

Figure 3. Receiver operating characteristics analysis for prediction of pathologic complete response to neoadjuvant chemotherapy. AUC=area under the curve.