Estrogen-receptor-directed neoadjuvant therapy for breast cancer: Results of a randomised trial using formestane and methotrexate, mitozantrone and mitomycin C (MMM) chemotherapy

Background: We wanted to determine whether neoadjuvant systemic chemoendocr ine therapy guided by the estrogen receptor (ER) status of the primary brea st cancer, followed by conventional surgery and/or radiotherapy, reduces lo cal and distant recurrence and improves survival compared with adjuvant tre atment given conventionally postoperatively. Patients and methods: Two hundred ten patients with primary breast cancer ( T-1-T-4, N-0, N1-2) were randomised to receive treatment with neoadjuvant c hemoendocrine therapy or conventional post-operative chemoendocrine therapy . Systemic therapy was based on the estrogen receptor (ER) status of the pr imary tumour obtained by trucut core biopsy. ER-negative patients received MMM chemotherapy (methotrexate (30 mg/m(2)), mitozantrone (7 mg/m(2)) and m itomycin (7 mg/m(2)) three-weekly for three months and ER-positive patients who were premenopausal received goserelin (3.75 mg monthly), and post meno pausal women formestane (250 mg every two weeks) over three months. Results: With a minimum of five years follow-up, there is no evidence of an y survival benefit from the pretreatment neoadjuvant therapy regimen, with five year overall survival being 79% +/- 4.7% (neoadjuvant) and 87% +/- 3.4 % (adjuvant). Similarly, there was no apparent benefit in terms of disease- free survival. There was, however, a significant reduction in the incidence of distant metastases in responders (4 of 51; 8%) compared with non-respon ders (17 of 49; 35%) (P < 0.01). There was a reduction in the need for surg ery in responding patients with T-1 and T-2 tumours, since 10 of 74 (14%) h ad no detectable residual tumour, without any apparent increase in the risk of local or distant recurrence. Conclusion: In this study neoadjuvant treatment with endocrine or chemother apy provided no obvious survival benefit to women with breast cancer. Howev er, it does allow avoidance of surgery in some cases. Also, the patients wh ose tumours respond to neoadjuvant systemic therapy have a lower incidence of distant metastases after five year follow-up compared to those whose tum ours fail to respond.