title: Suppression of ovarian function in combination with an aromatase inhibitor as treatment for advanced breast cancer in pre-menopausal women.
abstract: Trials have shown superiority of aromatase inhibitors (AIs) over tamoxifen for post-menopausal oestrogen receptor-positive advanced breast cancer (ER+ABC). We previously reported the use of goserelin plus anastrozole (G+A) as second-line endocrine therapy for pre-menopausal ER+ABC. We report clinical and endocrine data from G+A as first-line systemic therapy. Thirty-six patients (median age=44 years) with metastatic (N=28) and locally advanced disease were administered G+A for ≥6 months (unless progressed prior). Some (N=13) received further therapy with goserelin plus another AI (steroidal), exemestane (G+E). Serial serum hormone assays (oestradiol, dehydroepiandrosterone sulphate, testosterone, follicle stimulating hormone and luteinising hormone) were performed. Twenty-four patients (67%) derived clinical benefit (CB) (5% complete response, 31% partial response, 31% stable disease for ≥6 months) with median time to progression and duration of CB of 12 (2-47) and 24+(7-78+) months respectively. Ten patients were still receiving first-line G+A at analysis. Amongst 13 patients who went onto receive G+E, 38% achieved CB with a mean duration of 13+(7-32) months. Therapy was well tolerated with no withdrawals. The combination of G+A resulted in 98% reduction (from pre-treatment to 6-month) in median levels of oestradiol (from 574.5 pmol/L; inter-quartile range (IQR)=209-1426; (N=6) to 13.45 pmol/L; IOQ=5.5-31.5 (N=4) whilst the levels of other hormones had minimal fluctuations during therapy. The combinations of ovarian function suppression (using G) and AIs produce sustained CB and minimal side effects in pre-menopausal ER+ABC with significant reduction in oestradiol levels. Within the limitations of being a non-randomised study, they should be considered in appropriate patients with hormone-sensitive ABC.
authors.affiliation: Division of Breast Surgery, University of Nottingham, UK. kl.cheung@nottingham.ac.uk
authors.forename: K L
authors.initials: KL
authors.lastname: Cheung
authors.forename: A
authors.initials: A
authors.lastname: Agrawal
authors.forename: E
authors.initials: E
authors.lastname: Folkerd
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
authors.forename: J F R
authors.initials: JF
authors.lastname: Robertson
authors.forename: L
authors.initials: L
authors.lastname: Winterbottom
mesh_terms: D000328:Adult; D000077384:Anastrozole; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D007987:Gonadotropin-Releasing Hormone; D017273:Goserelin / Q000008:administration & dosage; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D010053:Ovary / Q000187:drug effects*; D017697:Premenopause; D013629:Tamoxifen / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D006728:Hormones; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D017273:Goserelin; D000077384:Anastrozole; D007987:Gonadotropin-Releasing Hormone; C056516:exemestane