Immunohistochemistry and Molecular Biology of Breast Cancers: Old and New Prognostic Factors

Abstract

Despite the realisation that breast cancer is composed of multiple distinct entities, decision making regarding management is still governed by basic clinicopathological features and three predictive markers (i.e. oestrogen and progesterone receptor, and HER2), used in combination as part of guidelines or in algorithms for informed decision making. Although successful in reducing the mortality of breast cancer patients, this approach does not allow for the individualisation of the therapy for breast cancer patients. High throughput molecular data on the different subtypes of breast cancer have led to the identification of new prognostic and predictive markers. The need for these is evident when one considers the poor positive predictive value of ER status for endocrine therapy, the modest efficacy of targeted agents as monotherapy, the variable prognostic relevance of tumour size in different subtypes and the limited prognostic value of grade in certain breast cancer subtypes. Furthermore, the increasing availability of targeted agents of different classes, in an environment of spiralling health costs, makes the identification of patient subgroups that will derive the most benefit from these new treatments of paramount importance. In this chapter we will first appraise the currently available tools for the identification of new predictive and prognostic markers, following which we will present a review of predictive and prognostic markers currently under investigation for clinical application, including assessment of their limitations and clinical applicability.