Breast cancer subtyping by immunohistochemistry and histological grade outperforms breast cancer intrinsic subtypes in predicting neoadjuvant chemotherapy response

Abstract

Intrinsic subtypes are widely accepted for the classification of breast cancer. Lacking gene expression data, surrogate classifications based on immunohistochemistry (IHC) have been proposed. A recent St. Gallen consensus meeting recommends to use this "surrogate intrinsic subtypes" for predicting adjuvant chemotherapy resistance, implying that "Surrogate Luminal A" breast cancers should only receive endocrine therapy. In this study we assessed both gene expression based intrinsic subtypes as well as surrogate intrinsic subtypes regarding their power to predict neoadjuvant chemotherapy benefit. Single institution data of 560 breast cancer patients were reviewed. Gene expression data was available for 247 patients. Subtypes were determined on the basis of IHC, Ki67, histological grade, endocrine responsiveness, and gene expression, and were correlated with chemotherapy response and recurrence-free survival. In ER+/HER2- tumors, a high histological grade was the best predictor for chemotherapy benefit, both in terms of pCR (p = 0.004) and recurrence-free survival (p = 0.002). The gene expression based and surrogate intrinsic subtype based on Ki67 had no predictive or prognostic value in ER+/HER2- tumors. Histological grade, ER, PR, and HER2 were the best predictive factors for chemotherapy response in breast cancer. We propose to continue the conventional use of these markers.

Fig. 1

RFS curves for subsequently the traditional IHC subtypes (log rank p value = 0.0002) (a), the PAM50 subtypes (log rank p value = 0.003) (b), the surrogate intrinsic subtypes-Ki67 (log rank p = 0.19) (c), the surrogate intrinsic subtypes-grade (log rank p = 0.003) (d), and endocrine sensitivity (log rank p = 0.0067) (e)