Abstract
Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus 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 diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 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 by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed 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 to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.
Highlights
Breast cancer is the most frequently diagnosed cancer in the women worldwide
The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen)
A strong correlation has been demonstrated between the conventional histopathological features reported on the formalin fixed paraffin-embedded (FFPE) tumor tissue and the molecular subclass identified by Gene expression profiling (GEP) on fresh tumor tissue (Cheang et al, 2008)
Summary
Breast cancer is the most frequently diagnosed cancer in the women worldwide. Enormous molecular and biological heterogeneity with impact on clinical course and response to chemotherapy has been reported. Gene Expression Profiling (GEP) has demonstrated that breast cancer consists of at least five distinct molecular subtypes (Perou et al, 2000; Sorlie et al, 2001). These subtypes have different risk factors (Phipps et al, 2011) and clinicopathologic features (Chang et al, 2008; Cheang et al, 2008; Liedtke et al, 2008; Smid et al, 2008; Onitilio et al, 2009; Chuthapisith et al 2012). The surrogate IHC markers for molecular breast cancer subtypes have emerged as a practical clinical tool for an approximate molecular classification of breast cancer patients in the developing countries. We here report the association of IHC defined molecular subclass with the clinical response to chemotherapy in these patients
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