Molecular Biology of Breast Cancer


Breast cancer is a common disease affecting approximately 1 in 9 women at some time in their lives. Moreover, it is not a single disease but is characterised by distinct pathological types with different clinical outcomes. In the past decade, considerable progress has been made in understanding these different cancer subtypes at the molecular level. In particular, global gene expression studies have identified five predominant subtypes that have unique expression signatures. Unlike many other cancers, where a hierarchy of genetic mutations that leads to tumourigenesis has been identified, breast tumours have diverse genetic mutations that affect a variety of signalling pathways. Recently, large‐scale whole‐genome sequencing has revealed a set of potential driver mutations for breast cancer. Although some highly successful treatments have been developed, the challenge for the future is the development of individualised therapies that are specific to each patient's tumour type.

Key Concepts

  • Breast cancer is a heterogeneous disease characterised by distinct pathological types with different outcomes.
  • Breast tumours have diverse genetic mutations that affect a variety of signalling pathways.
  • Breast tumours can be classified into different subgroups according to their molecular expression profiles.
  • It is not clear whether specific molecular pathways establish the subtype of breast cancer or whether different cell types become transformed and give rise to each tumour subtype.
  • Breast cancer patients would benefit from individual therapeutic regimens designed to treat their particular type of cancer.

Keywords: mammary gland; breast cancer; cell of origin; molecular classification; individualised therapy

Figure 1. The human mammary gland. (a) Schematic representation of the human mammary gland, comprising ducts, alveoli, adipose tissue and connective tissue, as indicated. (b) Section of a normal duct (top) and of a ductal carcinoma in situ (DCIS, bottom).
Figure 2. Adult mouse mammary gland. (a) Schematic representation of the structure and cellular composition of the mammary gland. (b) Immunofluorescence staining of representative sections of the mammary gland showing markers expressed in the basal (right) and in the luminal (left) layers of the ducts/alveoli. The antibodies used are highlighted in each section with CK14, CK18 and SMA in green and β‐casein (a milk protein expressed in alveoli), ERα and p63 in red. Nuclei are stained blue. Whole mounts of a virgin (left) and a pregnant (right) mouse mammary gland are also shown.
Figure 3. One model of the differentiation hierarchy in the mammary gland based on the presence of bipotent stem cells. Some of the markers used to distinguish specific populations are indicated.


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Further Reading

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Caffarel, Maria M, Pensa, Sara, Wickenden, Julie A, and Watson, Christine J(Nov 2016) Molecular Biology of Breast Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023164.pub2]