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The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.

One hundred and sixteen patients with locally advanced or metastatic breast cancer were randomized to receive CMF (cyclophosphamide 600 mg m(-2) day 1 and 8 i.v., 5-fluorouracil 600 mg m(-2) day 1 and 8 i.v., methotrexate 40 mg m(-2) day 1 and 8 i.v., monthly for 6 cycles) or MM (methotrexate 30 mg m(-2), mitoxantrone 6.5 mg m(-2), both i.v. day 1 3-weekly for 8 cycles) as first line treatment with chemotherapy. Objective responses occurred in 17 patients out of 58 (29%) who received CMF and nine out of 58 (15%) who received MM; 95% confidence interval for difference in response rates (-1%-29%), P = 0.07. No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged. There was, however, significantly reduced haematological toxicity (P < 0.001) and alopecia (P < 0.001) and fewer dose reductions and delays in patients randomized to MM. No statistically significant differences were seen between the two regimes in terms of quality of life (QOL). However, some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment. Despite the fact that results surrounding response rates and time to progression did not reach statistical significance, their possible compatibility with an improved outcome on CMF treatment must be borne in mind. However, MM is a well-tolerated regimen with fewer side-effects than CMF, which with careful patient management and follow-up, therefore, may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly.

Mitozantrone (Novantrone) has recently been incorporated into a new combination chemotherapy regimen with mitomycin-C and methotrexate (MMM) against advanced breast cancer. We have compared MMM (mitozantrone 8 mg m-2 i.v. q 3 weekly, methotrexate 35 mg m-2 i.v. q 3 weekly, mitomycin-C 8 mg m-2 i.v. q 6 weekly) with CMF (cyclophosphamide 100 mg orally, days 1-14, methotrexate 35 mg m-2 i.v., days 1 and 8, 5-FU 1,000 mg i.v., days 1 and 8, q 4 weekly), each regimen with folinic acid rescue, in a randomised trial, 29/57 evaluable patients treatment with MMM achieved an objective response (51%) compared with 33/55 treated with CMF (60%). Overall median survival was 16 months for MMM and 12 months for CMF. Subjective toxicity was low for both regimens and the only significant difference was in incidence of diarrhoea (50% for CMF vs 21% for MMM). Haematological toxicity was similar, leading to treatment delays and/or dose reductions in 35% patients with CMF vs 43% with MMM. Thrombocytopenia was significantly increased in MMM (34% vs 14%). No clinical cardiotoxicity was seen, but a significant reduction in left ventricular ejection fraction occurred in four patients on CMF vs 2 on MMM. MMM is an active, well tolerated new chemotherapy regimen for advanced/metastatic breast carcinoma with an efficacy and toxicity spectrum very similar to CMF.

Seventy-four post-menopausal women with metastatic breast cancer were treated with a combination hormonal regimen consisting of tamoxifen, aminoglutethimide danazol and medroxyprogesterone acetate (POND). 72% of the patients had received no previous treatment. The overall response rate (complete and partial remission) was 43.5% with a median response duration of 19 months and a median survival of 27 months. The most common sites of response were in regional nodes and local chest wall disease. The major side-effects were those expected from the individual agents: nausea, lethargy, rash and oedema.

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy. With a median follow-up of 19 months (range 6-42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease. Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.