Surrogate molecular classification of breast carcinoma: A classification in need or a dilemma indeed

Abstract

The biological heterogeneity of breast cancer accounts for variations in natural course of disease and differences in response to various therapeutic modalities. These variations pose as major challenges in clinical management of patient. The quest for markers that would accurately define prognosis and response to particular therapeutic modality has led us to the molecular makeup of these tumors. The technique of gene expression profiling has been pivotal in this regard. With the study of thousands of genes simultaneously in breast cancer patients, a molecular classification of breast carcinoma was proposed in the early 21st century. High-throughput commercial assays proved to be useful in predicting prognosis for the patients but are expensive. Classification of breast cancers using immunohistochemistry that can be used as a surrogate of this molecular classification is inexpensive, easier, and more convenient to use. However, the accuracy of this classification is closely dependent on accurate immunohistochemical measurement of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki67. The initial surrogate classification has undergone revisions to make it more relevant in the 13th St Gallen International Breast Conference. Newer molecular subtypes such as claudin low have also been identified but are included in the basal-like subtype in surrogate classification due to its triple-negative nature. The utility of the surrogate classification in the Indian setting is immense due to limited access to molecular techniques. This review covers in detail the evolution, prognostic, and therapeutic implications of the surrogate molecular classification of breast cancers.