Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy

TLDR

Breast cancer can be classified into luminal, basal‑like, normal‑like, and erbB2+ subgroups based on gene‑expression profiles, and these subtypes have distinct prognoses. This study aimed to determine whether these molecular subtypes differ in their response to preoperative chemotherapy. Eighty‑two tumors were sampled by fine‑needle aspiration before a paclitaxel‑followed‑5‑FU, doxorubicin, cyclophosphamide regimen, and gene‑expression profiling with Affymetrix U133A microarrays and the breast‑intrinsic gene set was used to assign molecular class. Basal‑like and erbB2+ tumors achieved the highest pathologic complete‑response rates (~45%), whereas luminal tumors had ~6% and normal‑like none; molecular class was not independent of conventional predictors, and distinct gene sets underlie response in the two ER‑negative subtypes, indicating that basal‑like and erbB2+ cancers are more sensitive to this chemotherapy than luminal and normal‑like cancers.

Abstract

Abstract Purpose: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Experimental Design: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported “breast intrinsic” gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. Results: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor–negative subtypes. Conclusions: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.