Genomics and circulating tumor cells: promising tools for choosing and monitoring adjuvant therapy in patients with early breast cancer?
OBJECTIVE
Gene expression profiling using a class discovery approach has consistently shown that breast cancer emerges as a group of different disease entities: the basal-like, the human epidermal growth factor receptor 2 type, the normal breast-like, and at least two different hormone receptor positive or luminal types. Initial reports have also suggested that certain expression patterns are associated with relapse. Current data on adjuvant therapy are only beginning to consider this biologic heterogeneity (estrogen receptor and human epidermal growth factor receptor 2 status). Similarly, the search for isolated tumor cells in blood or bone marrow has been regarded as another approach for defining prognosis and tailoring adjuvant therapies. The purpose of this review is to highlight the recent data emerging from both approaches as a means of assessing prognosis and tailoring therapy in patients with early breast cancer.


RESULTS
The initial reports on prognosis assessment of breast cancer using the expression profile have been corroborated, but the differences between the actual genes selected for the different prognostic signatures remain difficult to explain. Others have introduced added signatures, such as those associated with proliferation or with wound healing, or selected subgroups on the basis of, for example, estrogen receptor level prior to class comparison. The data on the quantification of expression of a limited number of selected genes are promising for both prognosis and prediction. The segregation of histological grade 2 tumors into genetically defined grade 1 or 3 tumors and its associated prognostic significance is a critical observation. The standardization of methods for measuring isolated tumor cells in blood or bone marrow has resulted in validated data both on prognosis in early breast cancer and in the advanced setting. Methylation of circulating DNA might become another method for selecting patients for extended adjuvant regimens.


CONCLUSIONS
The new molecular knowledge must be incorporated into prospective clinical studies in patients with early breast cancer. This is the challenge for the years to come.
Dirix
Luc
L
Oncology Center, Algemeen Ziekenhuis Sint-Augustinus, Antwerp, Belgium. luc.dirix@pandora.be
Van Dam
Peter
P
Vermeulen
Peter
P
D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics / Q000639:trends*; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis
D014408:Biomarkers, Tumor