We studied epidermal growth factor receptor (EGF-R) expression in rela
tion to steroid receptor status, flow cytometric DNA content and S-pha
se fraction (%S) in a selected case series of 129 ductal primary opera
ble breast cancer to determine the possible role of EGF-R in prognosis
assessment. EGF-R expression was positively related with proliferatio
n activity, suggesting that EGF-R could be involved in the regulation
of breast cancer cell growth. We found about 80% of highly proliferati
ng DNA aneuploid tumors in the EGF-R positive category, while the EGF-
R negative tumors showed a lower frequency of highly proliferating DNA
aneuploid tumors (57%), confirming the important role of EGF-R in bre
ast cancer aggressiveness and progression. No relationship between EGF
-R expression and steroid receptor status was observed. To better unde
rstand how EGF-R and estrogen receptor (ER) operate together to stimul
ate breast cancer cell growth we analyzed the %S in the two groups of
ER negative (ER-) and ER positive (ER+) tumors, stratifying the patien
ts on the basis of EGF-R tumor positivity. Here breast tumor prolifera
tion activity seems mainly to be induced by the stimulus of EGF-R, the
%S values of the EGF-R negative tumors in the ER- and ER+ groups bein
g 6.1 and 6.9%, respectively. Instead, the median %S of EGF-R positive
tumors was 10% in the ER- class and 14% in the ER+ group. The analysi
s of the percentages of 5-year patient disease free survival were 84%
for patients with EGF-R negative tumors and 61% for patients with EGF-
R positive lesions, respectively. The data reported here further show
the crucial role of EGF-R in breast cancer cell growth and that the EG
F-R overexpression is indicative of a poor prognosis.