Clinical predictors of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer

Abstract

The response of triple-negative breast cancer (TNBC) to chemotherapy is heterogeneous; particular subtype classifications based on mRNA gene expression analysis have been demonstrated to be associated with a pathological complete response (pCR). The aim of the present study was to investigate additional clinical and pathological characteristics associated with pCR status. The pathological and clinical characteristics of 40 TNBC patients who underwent neoadjuvant chemotherapy followed by surgery were retrospectively analyzed by dividing the cases into two groups according to the response to treatment: pCR (n=12) and non-pCR (n=28). Clinically, patients in the pCR group presented tumors with a significantly less advanced Tumor-Node-Metastasis stage (P=0.030) and mammographic calcification was less common (17 vs. 58%; P=0.034). Pathologically, whereas all cases in the pCR group (12/12, 100%) were of the histological type 'invasive ductal carcinoma, not otherwise specified' (IDC-NOS), the non-pCR group consisted of a lower proportion of IDC-NOS cases (20/28, 71%) and more cases of special histological types, including mucinous, metaplastic, medullary and apocrine carcinomas (P=0.079). The positive rates of androgen receptor (AR) and forkhead-box A1 (FOXA1) tended to be lower in the pCR group (AR, 0 vs. 29%, P=0.079; FOXA1, 8 vs. 29%, P=0.233). The Ki-67 score was significantly higher in the pCR group than in the non-pCR group (P=0.041). The results suggest that patients with TNBC who present with clinically less advanced tumors and less frequent mammographic calcification are more likely to respond to chemotherapy. From a pathological standpoint, IDC-NOS type, negative AR status and higher Ki-67 scores may be associated with chemotherapy sensitivity.

Keywords: androgen receptor; mammographic calcifications; neoadjuvant chemotherapy; pathological complete response; triple-negative breast cancer.

Figure 1.

IHC staining of AR and FOXA1. All images are magnification, ×100. (A and B) Hematoxylin and eosin staining of triple-negative IDC tissue. Representative IHC image with (C) positive and (D) negative nuclear staining for AR in triple-negative IDC tissue. Representative IHC image with (E) positive and (F) negative FOXA1 nuclear staining in triple-negative IDC tissue. A, C and E are images from a singular specimen, and B, D and F are another set of images from a different singular specimen. IHC, immunohistochemistry; AR, androgen receptor; FOXA1, forkhead-box A1; IDC, invasive ductal carcinoma.

Figure 2.

Box-and-whisker plot of the association between pCR and the immunohistochemical staining results for Ki-67, FOXA1 and AR. Circles indicate the outlier values, and asterisks indicate the extreme outlier values. The positive rate for AR was revealed to be significantly lower in the pCR group (P=0.043, Mann-Whitney U test). pCR, pathological complete response; FOXA1, forkhead-box A1; AR, androgen receptor.