The ability to diagnosis breast cancer at an earlier stage and the developm
ent of a wider range of treatment options have stimulated the search for mo
re refined criteria to select the subgroup of patients who develop recurren
t disease despite the absence of nodal involvement at the time of tumor res
ection. Such criteria include biologic parameters of prognostic relevance,
especially those that can be applied to routinely processed tissue sections
, as they allow a correlation with established histologic features of progn
ostic relevance. The biologic parameters can be divided into those which ar
e intrinsic characteristics of the tumors cells and those related to the in
teraction of tumor and the immediate microenvironment, the latter factors i
nfluencing invasiveness and metastatic potential. Steroid hormone receptor
expression, tumor growth fraction estimation, growth factors and their rece
ptors, and tumor suppressor gene proteins can now be assessed by immunostai
ning of routinely processed tissue sections. Whereas the assessment of othe
r parameters such as bcl-2 and Bar proteins, nm23 metastasis suppressor gen
e expression, vimentin, and other genes related to cyclin-dependent kinase
activity can also be done immunohistochemically, their worthiness as progno
stic parameters require further studies. Factors related to tumor-stromal i
nteraction include angiogenesis, adhesion molecules, cytoskeletal proteins,
extracellular matrix proteins and proteases, all of which are potentially
useful prognostic indices and also hold promise for newer avenues of therap
eutic intervention.