Pathways to breast cancer recurrence

Abstract

Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of "recurrent" disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence.

Figure 1

Current understanding of breast tumor recurrence. Breast cancers localized at primary breast location and treated early can still relapse due to (a) existence of cancer stem cells and (b) transformation of cancer cells into a relatively aggressive phenotype. Cancer stem cells as well as transformed cancer cells are resistant to conventional therapies and highly metastatic. Recurrent breast cancers are typically marked by high percentage of aggressive cells.

Figure 2

Multiple factors that define the “stemness” in cancer stem cells.

Figure 3

Complex interplay of factors that influence breast cancer recurrence. The various molecular determinants of tumor recurrence are very intricately connected and interregulated, making it difficult to establish a hierarchical sense.