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Management of breast cancer with targeted agents: importance of heterogenicity

Nature Reviews Clinical Oncology volume 7, pages 139–147 (2010)Cite this article

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A Correction to this article was published on 01 April 2010

Abstract

Breast cancer is a heterogeneous disease with different molecular drivers regulating its growth, survival and response to therapy. Breast cancer is divided in three major subtypes based on the pattern of expression of hormone receptors and HER2: luminal tumors (or HR positive), HER2 amplified tumors, and the remaining subtypes being collectively referred to as triple-negative breast cancer. While tumors within these subtypes have similar gene-expression patterns, clinical outcomes, and response to therapy, this division is far from perfect and subgroups within these groups are beginning to be identified. In terms of therapy, an increasingly rational drug development effort has resulted in agents against new molecular targets that are active against only those tumors with the targeted molecular alteration or phenotype. These agents include receptor and non-receptor tyrosine kinase inhibitors (HER1, HER2, HER3, insulin-like growth factor receptor, c-met, fibroblast growth factor receptor and HSP 90 inhibitors), intracellular signaling pathways (PI3K, AKT, mTOR), angiogenesis inhibitors and agents that interfere with DNA repair (PARP inhibitors). Thus, the overall management of breast cancer will increasingly require an understanding of breast cancer heterogeneicity, the biological nature of any given tumor as well the existence of increased personalized treatment options.

Key Points

  • Breast cancer is a heteregenous disease divided in three major subtypes: HR positive, HER2 amplified, and triple negative; the clinical outcomes and treatments are different for each subgroup

  • The estrogen receptor, receptor tyrosine kinase and DNA repair pathways are key to understanding the growth and progression of invasive breast cancer and how interference of these pathways results in anti-cancer activity

  • A high number of molecular targeted agents are under clinical development and combinatorial approaches will probably become the norm

  • Targeted agents currently used in clinical practice are the anti-HER2 monoclonal antibody trastuzumab, the dual HER1/HER2 tyrosine kinase inhibitor lapatinib, and the anti-VEGF antibody bevacizumab

  • Studies with compounds targeting non-receptor tyrosine kinase (src), signaling pathways downstream of growth factor receptors (mTOR, PI3K, HSP90), and DNA repair mechanisms (PARP) have shown promising clinical activity

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Figure 1: Targeted therapeutics against HR-positive breast cancer.

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  1. Medical Oncology Department, Breast Cancer Center, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Pg. Vall d'Hebron, 119–129, Barcelona, 08035, Spain

    Serena Di Cosimo & José Baselga

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Correspondence to José Baselga.

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J. Baselga declares he is a Consultant for Exelixis, Merck, Novartis and Roche. S. Di Cosimo declares no competing interests.

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Di Cosimo, S., Baselga, J. Management of breast cancer with targeted agents: importance of heterogenicity. Nat Rev Clin Oncol 7, 139–147 (2010). https://doi.org/10.1038/nrclinonc.2009.234

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