Association of Immunohistochemically Defined Molecular Subtypes with Clinical Response to Presurgical Chemotherapy in Patients with Advanced Breast Cancer

Abstract

Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with differentclinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive andnot available in the developing countries where the majority of patients present at advanced stage. The St GallenConsensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR,HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosedpatients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtypewith the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the thirdcycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like andHER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively.Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer(TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed byHER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity wasobserved within each subgroup, being most marked in the TNBC although the most responding tumors, 8%developing clinical-progressive-disease. The study supports association of molecular subtypes with response tochemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.