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Histological and molecular types of breast cancer: is there a unifying taxonomy?

Nature Reviews Clinical Oncology volume 6, pages 718–730 (2009)Cite this article

Abstract

Breast cancer is a complex and heterogeneous disease, comprising multiple tumor entities associated with distinctive histological patterns and different biological features and clinical behaviors. Microarray-based high-throughput technologies have been employed to unravel the molecular characteristics of breast cancer, including its proclivity to disseminate to distant sites, and the molecular basis for histological grade. In addition, a breast cancer molecular taxonomy based solely on transcriptomic analysis has been proposed. Most microarray studies have focused on invasive ductal carcinomas of no special type, neglecting the important information about the biology and clinical behavior of breast cancers conveyed by histological type. Histological special types of breast cancer account for up to 25% of all invasive breast cancers. The histopathological characteristics of these cancers might be driven by specific genetic alterations, providing direct evidence for genotypic–phenotypic correlations between morphological patterns and molecular changes in breast cancer. We review the historical aspects of breast cancer taxonomy, discuss the possible origins of the diversity of breast cancer and propose an approach for the identification of novel therapeutic targets on the basis of histological special types of breast cancer.

Key Points

  • Breast cancer special types account for up to 25% of all invasive breast cancers and have distinct histological features and clinical implications

  • The relative rarity of each type, other than lobular, tubular, medullary and metaplastic tumors, renders them difficult to study in advanced molecular studies

  • Some special types of breast cancer are driven by a constellation of specific genetic aberrations (for example, metaplastic breast cancers often harbor dysfunctional p53 and BRCA1 pathways)

  • Each special type, apart from invasive lobular and apocrine carcinomas, is more homogeneous than invasive ductal carcinomas of no special type at the genomic, transcriptomic and immunohistochemical levels

  • Owing to their more homogeneous molecular make-up, studying special types of breast cancer could lead to the identification of novel therapeutic targets

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Figure 1: Histological special types of breast cancer.
Figure 2: Histological special types and molecular subtypes.
Figure 3: Theoretical models that explain breast cancer histological special types.
Figure 4: The low-grade breast neoplasia family.

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Acknowledgements

The authors are grateful to Felipe Geyer for his insightful comments and entertaining discussions about the actual morphological features of special types of breast cancer and Dr. Kay Savage for the excellent histological sections. This manuscript is dedicated to the late Dr. Hans Peterse, an outstanding diagnostic histopathologist and a good friend, and to Dr. David Page, Prof Vincenzo Eusebi, Prof Ian Ellis, Prof Christopher Elston, Dr. Paul Peter Rosen and Prof John Azzopardi, whose pioneering work paved the way for a modern breast cancer taxonomy. We apologize to those investigators whose work we could not cite due to space constraints.

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  1. Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK

    Britta Weigelt

  2. Molecular Pathology Team, Breakthrough Breast Cancer Research Center, Institute of Cancer Research, London, UK

    Jorge S. Reis-Filho

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Weigelt, B., Reis-Filho, J. Histological and molecular types of breast cancer: is there a unifying taxonomy?. Nat Rev Clin Oncol 6, 718–730 (2009). https://doi.org/10.1038/nrclinonc.2009.166

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