Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive
ductal carcinoma,
lobular carcinoma,
medullary carcinoma,
mucinous carcinoma,
tubular carcinoma, and apocrine
carcinoma among others. Pure apocrine
carcinomas represent about 0.5% of all invasive breast
cancers according to the Danish
Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between benign apocrine changes and
breast carcinoma is unclear and has been a matter of discussion for many years. Recent
proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine
biomarkers [15-
hydroxyprostaglandin dehydrogenase (15-PGDH) and hydroxymethylglutaryl
coenzyme A reductase (
HMG-CoA reductase)] present in early and advanced apocrine lesions. These
biomarkers in combination with
proteins found to be characteristically upregulated in pure apocrine
carcinomas (
psoriasin, S100A9, and p53) provide a
protein expression signature distinctive for benign apocrine metaplasias and apocrine cystic lesions. These studies have also presented compelling evidence for a direct link, through the expression of the
prostaglandin degrading
enzyme 15-PGDH, between early apocrine lesions and pure apocrine
carcinomas. Moreover, specific
antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine
carcinoma. Finally, the identification of
proteins that characterize the early stages of mammary apocrine differentiation such as
15-PGDH,
HMG-CoA reductase, and
cyclooxygenase 2 (COX-2) has opened a window of opportunity for pharmacological intervention, not only in a therapeutic manner but also in a chemopreventive setting. Here we review published and recent results in the context of the current state of research on breast apocrine
cancer.