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The data on 91 patients (aged 30–78 years) with inoperable locally advanced breast cancer treated by primary chemotherapy and radiation therapy from 1980 to 1995 in the Breast Oncology Unit, Cardiff were analysed. Four chemotherapy regimens were used: 1) doxorubicin 40 mg/m 2 + vincristine 1 mg/m 2 (AV), three cycles; 2) mitozantrone 14 mg/m 2 (MZ), three cycles; 3) cyclophosphamide 600 mg/m 2 , methotrexate 40 mg/m 2 , 5-fluorouracil 600 mg/m 2 (CMF), six cycles; 4) cyclophosphamide 600 mg/m 2 , adriamycin/epirubicin 50 mg/m 2 , 5-fluorouracil 600 mg/m 2 (CAF/CEF), six cycles. The breast and glandular areas were irradiated to 40–50 Gy in 15–25 fraction (+/-5–10 Gy boost in two-to-five fractions. The overall response rate to chemotherapy was 61% (95% confidence interval 51–71%) with 13% CR (6–20%). Thirteen patients underwent mastectomy for operable persistent disease. Ten patients had uncontrolled inoperable local disease after primary therapy; 61 patients have relapsed, 69% due to metastases, (15% synchronous with local relapse), 31% local failure only. The overall 2−, 5− and 10-year survival rates are 54% (42–66%), 28% (16–40%) and 11% (1–21%) respectively. These results confirm that metastasis rather than local failure dictates the poor outcome in these patients and that breast conservation can be achieved.

139 peri- and postmenopausal women with advanced or recurrent breast cancer who had not received prior hormonal therapy were randomised in an open, cross-over study comparing the synthetic progestogen megestrol acetate with tamoxifen. The response rate (CR/PR) to megestrol acetate (25%; 95% confidence interval (CI) 15-35%) was not significantly different from that produced by tamoxifen (33%, CI 22-44%). Time-to-treatment failure was also similar in the two groups. Cross-over treatment was given on progression in 76 cases. Cross-over response (CR/PR) was seen in 3 of 35 patients (9%) receiving megestrol acetate as second-line therapy and in 6 of 41 patients (15%) receiving tamoxifen second-line. There was no significant difference in survival between the groups (P = 0.17) with median survival times of 24 and 32 months for the megestrol acetate and tamoxifen groups, respectively. The toxicity profile of the two drugs was different, although significant toxicity was rare with either agent. Megestrol acetate is an effective treatment for advanced breast cancer in older women when used either as first- or second-line treatment. Cross-over response is seen following both treatments. Given that most patients now receive tamoxifen as adjuvant treatment, megestrol acetate would appear to be one of the logical choices for patients who find the side-effects of tamoxifen unacceptable and for those who relapse on tamoxifen with further hormone therapy being clinically indicated.

Neoadjuvant chemotherapy is showing promising results in the primary treatment of breast cancer. We have analysed the data on 91 patients (age 30–78 years) representing 15 years of experience firm 1980–1995 in our unit. All patients had advanced tumours, 69% being T4 (46% of these inflammatory), with 76% of tumours more than 5 cm in size and 68% clinically node positive at diagnosis. Four chemotherapy regimens have been used: (1) Ariamycin 40 mg/m2 + Vincristine 1 mg/m3 × 3 cycles. (2) Mitozanstrone 14 mg/m2 × 3 cycles. (3) Cyclophosphemide 500–600 mg/m2, Methotrexate 40–50 mg/m2, 5 Fluorouracil 500–600 mg/m2 (CMF) × 3–6 cycles. (4) Cyclophosphamide 500–600 mg/m2, Adriamycin/Epirubicin 40–50 mg/m2, 5 Fluorcuracil 500–600 mg/m2 (CAF/CEF) × 3–6 cycles. The breast and glandular areas were irradiated with 40–50 Gy in 15–25 fractions ± 5–10 Gy boost in 2–5 fractions. The overall 2, 5 and 10 year actuarial survival rates are 54%, 28% and 11% respectively. Overall response rates to chemotherapy were 61% (14% CR). Response rates were highest [92% (50% CR)] with CAF/CEF based regimens. The addition of radiotherapy increased the response rate to 93% overall, and with CAF/CEF there was a 75% CR rate. The median time to maximum clinical response was 5 months and 9 months on radiological criteria. Sixty-one patients have relapsed, 54% due to metastases, 15% synchronous local and metastatic disease, 31% local failure only. Thirty-one percent of patients had mastectomy, with only 10% of patients having uncontrolled inoperable local disease after therapy.

A prospective study of pre-treatment general immune competence in breast cancer patients has been instituted to determine its relationship to recurrence and its clinical value in predicting prognosis. A 2 yr follow-up has been completed on 198 patients. The tests of immune competence, all completed before treatment was commenced, were total WBC, absolute and percentage lymphocyte counts, serum immunoglobulins (IgG, IgA and IgM), lymphocyte transformation with PHA and delayed cutaneous hypersensitivity responses to tuberculin PPD and dinitrochlorobenzene (DNCB). None of these pre-treatment tests was predictive for recurrence or prognosis when the effects of stage-related immunosuppression were excluded by analysing the results within each clinical stage. Hence for those patients who developed recurrence within 2 yr , pretreatment immunological status gave no additional prognostic information over conventional clinico-pathological data.

Up to fifteen plasma proteins were measured before treatment in 249 women presenting with lumps in the breast. Concentrations showed considerable overlap between the various clinical stages, and were often normal even in metastatic disease. A discriminant function is proposed, based on measurement of C-reactive protein, beta 2-microglobulin, carcinoembryonic antigen and ferritin and calculation of a score for each subject. High-risk scores resulted for all 18 patients with Stage 4 (i.e., metastatic) disease, and the number of Stage 1 patients attaining high scores was consistent with the reported incidence of development of metastases in such a group. Follow-up studies are in progress.