The proto-oncogene bcl-2 is demonstrated to block a final common pathw
ay leading to apoptosis and is expressed in more than half of human br
east cancers. Invasive breast cancer has reduced bcl-2 immunostaining
compared with normal breast epithelia and preinvasive breast lesions.
As an inhibitor of apoptosis, bcl-2 should correlate with highly aggre
ssive tumor biology and resistance to hormonal/ cytotoxic therapy. How
ever, high bcl-2 expression has been shown to associate with a number
of favorable prognostic factors including ER positivity, PgR positivit
y, low histological grade, well-differentiated tumor, absence of c-erb
B-2 and p53. Unexpectedly, numerous studies have shown that tumors wit
h high bcl-2 expression are more responsive to hormone therapy and hav
e more favorable disease-free and overall survival. The clinical signi
ficance of bcl-2 in tumorigenesis and prognosis of breast carcinomas f
rom the data recently published are reviewed. Its role in modulation o
f hormonal/cytotoxic therapy and future directions are also discussed.