Abstract

Abstract C‐ erb B‐2 protein over‐expression was studied immunohis‐tochemically in 319 paraffin‐embedded breast carcinomas representing 89% of all breast‐cancer cases operated in the Tampere University Hospital between 1977 and 1981. The immunohistochemical evaluation of c‐ erb B‐2 was optimized using protease pre‐treatment and verified using antibodies for both the external and the internal domains of the protein. c‐ erb B‐2 over‐expression was found in 72 (23%) of the 319 cases and was associated with high histological and nuclear grade ( p < 0.0001), DNA aneuploidy ( p = 0.003), high tumor S‐phase fraction ( p < 0.000l), and lack of estrogen ( p < 0.0001) and progesterone ( p = 0.03) receptors. Overall, breast‐cancer patients with c‐ erb B‐2 over‐expression had about 2.2‐fold relative risk (RR) of death ( p < 0.001) as compared with those without over‐expression. According to a multivariate analysis, c‐ erb B‐2 over‐expression was an independent prognostic factor in the whole material as well as in the node‐negative sub‐set. In node‐negative breast‐cancer tumor size, S‐phase and c‐ erb B‐2 status defined a large patient group with only 4% 5‐year and 15% 10‐year mortality rate without adjuvant therapy. In comparison with c‐ erb B‐2‐negative tumors, those with over‐expression of this gene metastasized 3 times more often ( p = 0.0002) to the lungs, liver and brain and 3 times less often to the bone. Our findings suggest that the prognostic value of c‐ erb B‐2 over‐expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.