Review
Molecular and Cellular Heterogeneity in Breast Cancer: Challenges for Personalized Medicine

https://doi.org/10.1016/j.ajpath.2013.08.002Get rights and content
Under a Creative Commons license
open access

Breast cancer is noted for disparate clinical behaviors and patient outcomes, despite common histopathological features at diagnosis. Molecular pathogenesis studies suggest that breast cancer is a collection of diseases with variable molecular underpinnings that modulate therapeutic responses, disease-free intervals, and long-term survival. Traditional therapeutic strategies for individual patients are guided by the expression status of the estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor 2 (HER2). Although such methods for clinical classification have utility in selection of targeted therapies, short-term patient responses and long-term survival remain difficult to predict. Molecular signatures of breast cancer based on complex gene expression patterns have utility in prediction of long-term patient outcomes, but are not yet used for guiding therapy. Examination of the correspondence between these methods for breast cancer classification reveals a lack of agreement affecting a significant percentage of cases. To realize true personalized breast cancer therapy, a more complete analysis and evaluation of the molecular characteristics of the disease in the individual patient is required, together with an understanding of the contributions of specific genetic and epigenetic alterations (and their combinations) to management of the patient. Here, we discuss the molecular and cellular heterogeneity of breast cancer, the impact of this heterogeneity on practical breast cancer classification, and the challenges for personalized breast cancer treatment.

Cited by (0)

Supported by Friends for an Earlier Breast Cancer Test, the Susan G. Komen Breast Cancer Research Foundation, the National Cancer Institute, and the University Cancer research Fund of the University of North Carolina School of Medicine.

This article is part of a review series on the molecular pathogenesis of breast cancer.