SummaryThe relationship between c-erbB-2 gene expression (assessed immunohistochemically), S-phase fraction (SPF) and prognosis has been analysed in 172 women with primary breast cancer. c-erbB-2 staining was independent of age, tumour size, number of nodes involved, tumour grade and DNA ploidy, but was more common in oestrogen receptor (ER) negative tumours (P = 0.02) and progesterone receptor (PgR) negative tumours (P = 0.03). A weak correlation between c-erbB-2 staining and SPF was observed (r = 0.18). Amongst women with node negative disease, SPF was significantly related to relapse free survival (RFS, P = 0.04) while c-erbB-2 staining was not (P = 0.2). In contrast, both SPF (P = 0.002) and c-erbB-2 staining (P = 0.016) provided significant prognostic information on RFS for women with node positive disease. Multivariate analysis showed that c-erbB-2 staining and SPF gave independent information on RFS for women with node positive disease.

Summary DNA index and S-phase fraction (SPF) were Multivariate analysis using the Cox model suggested that, while SPF gave prognostic information independent of tumour size or nodal status, this independent significance was lost when histological grade was included in the analysis.

Summary Thirty-six consecutive patients with breast cancer and liver metastases with abnormal liver biochemistry were treated with epirubicin 25 mg m-2 i.v. weekly. No dose modification was made for abnormal liver biochemistry, but dose intensity was adjusted by delaying treatment according to myelosuppression. The UICC overall response rate according to UICC criteria was 11/36 (30%) and median response duration was 27 weeks. Liver biochemistry improved in a further seven patients. Treatment was well tolerated. Epirubicin given in this way is effective in patients with breast cancer and liver metastases. An initial deterioration in liver biochemistry may occur before there is a response to epirubicin.Liver metastases are common in patients with advanced breast cancer. The prognosis is worse for these patients than after recurrence in either soft tissue (Fentiman et al., 1986) or bone (Coleman & Rubens, 1987 Group, 1986). The administration of chemotherapy may be complicated by the liver's role in both cytotoxic drug activation, as for cyclophosphamide (Bagley et al., 1973), and metabolism, as with doxorubicin (Benjamin et al., 1974). Moreover, although anthracyclines are the most active single agents in patients with breast cancer (Steiner et al., 1983), toxicity can be severe in patients with impaired liver function and reduced hepatic drug clearance (Benjamin et al., 1974).Epirubicin (4'-epidoxorubicin) is a new anthracycline, structurally related to doxorubicin and with similar activity in patients with advanced breast cancer (Brambilla et al., 1986). It is eliminated more rapidly than doxorubicin (Camaggi et al., 1988) and, at equimolar doses, is less toxic than doxorubicin (Brambilla et al., 1986). We report our experience of the efficacy and toxicity of epirubicin in patients with breast cancer and liver metastases who have abnormal liver biochemistry.Patients received a low dose of epirubicin on a weekly schedule, with the aim of giving a high dose intensity whilst minimising toxicity. Patients and methodsThirty-six patients with histologically proven breast cancer, progressive liver metastases and abnormal liver biochemistry were entered into this phase II study.

No abstract

Mitoxantrone was given to 19 patients with liver metastases from breast cancer and biochemical evidence of liver dysfunction. In all, 2 patients received the drug at a dose of 10 mg/m2 on days 1 and 2 of the first course of treatment; 1 patient was given 9 mg/m2 and 17 received 8 mg/m2. Subsequent courses were given at a dose of 10 mg/m2. Three patients (16%) showed a partial response, with time to progression of between 3 and 7 months. Toxicity was considerable, with myelosuppression being the major problem.