Breast cancer: origins and evolution
Kornelia Polyak
Kornelia Polyak
Published November 1, 2007
Citation Information: J Clin Invest. 2007;117(11):3155-3163. https://doi.org/10.1172/JCI33295.
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Science in Medicine

Breast cancer: origins and evolution

Abstract

Breast cancer is not a single disease, but rather is composed of distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity is key for the development of targeted cancer-preventative and -therapeutic interventions. Current models explaining inter- and intratumoral diversity are the cancer stem cell and the clonal evolution hypotheses. Although tumor initiation and progression are predominantly driven by acquired genetic alterations, recent data implicate a role for microenvironmental and epigenetic changes as well. Comprehensive unbiased studies of tumors and patient populations have significantly advanced our molecular understanding of breast cancer, but translating these findings into clinical practice remains a challenge.

Authors

Kornelia Polyak

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Figure 4

Hypothetical models explaining intratumoral heterogeneity and tumor evolution.

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Hypothetical models explaining intratumoral heterogeneity and tumor evol...
(A) Based on the cancer stem cell hypothesis, differentiated cancer cells are progeny of cancer stem cells and they are not able to undergo self-renewing cell division. Thus, only the cancer stem cell can accumulate additional genetic changes that can drive tumor progression and drug resistance. (B) Based on the clonal evolution model, tumor cell phenotypes are determined based on the combination of cell type of origin of the tumor-initiating cell, acquired genetic and epigenetic alterations, and paracrine signals from surrounding cells. Cellular phenotypes are not stable and can change as the tumor evolves. All tumor cells have the capacity to undergo self-renewing division; thus they all have the potential to contribute to tumor progression and drug resistance. The two models do not have to be mutually exclusive, and their combination (e.g., clonal evolution of cancer stem cells) is also plausible.