title: Ovarian function suppression and fulvestrant as endocrine therapy in premenopausal women with metastatic breast cancer.
abstract: BACKGROUND
  Endocrine therapy is the preferred treatment for hormone-receptor (HR) positive metastatic breast cancer. In premenopausal patients, ovarian function suppression with goserelin in combination with anastrozole yielded promising results in phase II studies. Fulvestrant, a pure antioestrogen, yields high rates of disease stabilisation in postmenopausal women. Therefore, we investigated the feasibility and safety of fulvestrant plus goserelin in premenopausal women with HR-positive metastatic breast cancer.
  
  
  METHODS
  Premenopausal patients with metastatic breast cancer eligible for endocrine treatment received fulvestrant 250 mg and goserelin 3.6 mg every four weeks as first- to fourth-line therapy. Clinical benefit rate (CBR; response rate plus disease stabilisation ≥ 6 months) was defined as the primary study end-point. Time to progression (TTP) and overall survival (OS) were estimated using the Kaplan-Meier product limit method.
  
  
  RESULTS
  Twenty-six patients received treatment as scheduled. 81% were pre-treated with tamoxifen and 69% had received prior aromatase inhibitors in combination with goserelin. The majority of patients (69%) presented with visceral metastases. Complete response was observed in a single patient, partial response in three and disease stabilisation ≥ 6 months in eleven patients, resulting in a CBR of 58%. Median TTP was 6 months (95%confidence interval (CI), 2.4-9.6) and OS 32 months (95%CI, 14.28-49.72), respectively.
  
  
  CONCLUSIONS
  Results suggest that the combination of fulvestrant and goserelin offers promising activity in premenopausal patients and further investigation is warranted.
authors.affiliation: Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bago-Horvath
authors.forename: Anna
authors.initials: A
authors.lastname: Berghoff
authors.forename: Catharina
authors.initials: C
authors.lastname: DeVries
authors.forename: Ursula
authors.initials: U
authors.lastname: Pluschnig
authors.forename: Peter
authors.initials: P
authors.lastname: Dubsky
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Robert M
authors.initials: RM
authors.lastname: Mader
authors.forename: Andrea
authors.initials: A
authors.lastname: Rottenfusser
authors.forename: Florian
authors.initials: F
authors.lastname: Fitzal
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.forename: Guenther G
authors.initials: GG
authors.lastname: Steger
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D017697:Premenopause
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D017273:Goserelin; D000077267:Fulvestrant; D004958:Estradiol