13IN - Introduction: Luminal A and B: How Curable are they?

Abstract

ABSTRACT Hormone receptor positive (HR+) breast cancers can be separated by molecular subtyping into luminal A breast cancer (LUM A), which is more prevalent though less aggressive, and luminal B breast cancer (LUM B), which is associated with higher grade, increased proliferation rates, and an overall poorer prognosis. Other than genetic molecular subtyping, which can be expensive and not readily available, it may be possible to differentiate between these two subgroups using immunohistochemical assessment of the proliferative marker Ki67, as reported by Cheang et al, where a cut off of Ki67 14% was used. This method of assessment demonstrated utility in providing prognostic information, however the false positive and false negative rates were around 25%, suggesting there is significant room for improvement within such a method, and thus highlighting an area for ongoing research. Methodology aside, differentiation of HR+ breast cancers by molecular subgroups is critical, in order to identify appropriate treatment options for patients. Generally, endocrine therapy alone would be recommended for LUM A, which carries an excellent ten year breast cancer specific survival rate of approximately 90%. However, tumor dormancy and late recurrences beyond 10 years are characteristic of LUM A. There is a significant lack of knowledge of the mechanisms behind tumor dormancy, highlighting a crucial area for further research. Additionally, the optimal manner and duration of endocrine therapy in either pre- or postmenopausal women is, as yet, unknown; extension of endocrine treatment beyond 5 or even 10 years, as well as the most effective endocrine therapy agent, requires ongoing study to better define treatment algorithms for LUM A. LUM B, which is inherently more aggressive, requires more aggressive therapy and thus is generally treated with both endocrine therapy and chemotherapy, though this approach is not always effective. Potential alternate or additional treatment options may include targeting of other pathways of importance in this subgroup. This therefore requires firstly identification of pathways active in LUM B, and secondly, development and assessment of targeted agents against these pathways. The utility of inhibitors against mTOR, PI3K or IGFR-1 is of particular interest. Disclosure All authors have declared no conflicts of interest.