J. R. Farndon

EPIDERMAL-GROWTH-FACTOR RECEPTORS AND OESTROGEN RECEPTORS IN HUMAN BREAST CANCER

Competitive binding and monoclonal antibody staining techniques were used to demonstrate high-affinity (Kd = 1.9 nmol/l) receptors for epidermal growth factor (EGF) in 35 of 104 primary human breast tumours and in 10 of 14 secondary lymph-node deposits. There was a significant inverse relation between the presence of EGF receptors and the presence of oestrogen receptors in the primary tumours (p less than 0.01), and EGF receptors were found in a greater proportion of metastases than primary tumours (p less than 0.01). These results suggest that the presence of EGF receptors is associated with metastatic potential and that the growth of a proportion of poor-prognosis oestrogen-receptor-negative tumours may be regulated by peptide growth factors interacting with the EGF receptor.

EXPRESSION OF EPIDERMAL GROWTH FACTOR RECEPTORS ASSOCIATED WITH LACK OF RESPONSE TO ENDOCRINE THERAPY IN RECURRENT BREAST CANCER

Epidermal growth factor receptors (EGFR) and oestrogen receptors (ER) were analysed in 221 patients with primary operable breast cancer by means of radioligand assays. After median follow-up of 24 months (range 3-60 months), there had been recurrences in 99 patients, of whom 72 (median age 56 years, range 32-77 years) received tamoxifen alone as first-line treatment for recurrence. 20 patients (28%) showed a response to this therapy and 52 (72%) did not. Of 32 ER-positive tumours, 12 (37.5%) showed an objective response to tamoxifen compared with only 2 of 40 (5%) ER-negative tumours (p less than 0.005). Of 35 EGFR-positive tumours, 3 (8.5%) achieved an objective response compared with 11 of 37 (30%) EGFR-negative tumours (p less than 0.05). Only 1 of 28 EGFR-positive, ER-negative tumours achieved an objective response. Including patients whose disease remained stable for more than 6 months with the responders, however, EGFR status was a better predictor of response to tamoxifen; 15 of 37 EGFR-negative patients and 5 of 35 EGFR-positive patients responded (p less than 0.01), compared with 13 of 32 ER-positive and 7 of 40 ER-negative patients (not significant). EGFR expression is a highly significant marker of poor prognosis in patients with breast cancer; it appears to be as good a predictor as ER for objective response and better for overall response to endocrine therapy on relapse.

Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer

132 patients with advanced recurrent breast cancer were treated with four courses of mitozantrone 14 mg/m2 intravenously every 3 weeks (9 weeks). Patients showing disease stabilisation or objective response were randomised to stop chemotherapy or to continue until disease progression. At that stage 27% showed partial responses, 3% complete responses, and 10% disease stabilisation. 22 patients were randomised to continue chemotherapy and 21 to stop. There was no difference in time to disease progression, response duration, or survival between the two groups. Toxicity was mild during the first four courses of therapy. Thus, short courses of single-agent chemotherapy can produce similar therapeutic results to long-term chemotherapy, which has major implications for cost, resource allocation, and toxicity of therapy. Stopping chemotherapy early in responders did not cause rapid relapse. Since drug resistance apparently develops early during therapy, new approaches to modify resistance should be more useful than continuous chemotherapy.