title: A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.
abstract: BACKGROUND
  Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies.
  
  
  METHODS
  We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence.
  
  
  RESULTS
  After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen.
  
  
  CONCLUSIONS
  The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.
authors.affiliation: Division of Medical Oncology, Ospedali Galliera, Genova; Divisions of.
authors.forename: A
authors.initials: A
authors.lastname: DeCensi
authors.forename: B
authors.initials: B
authors.lastname: Bonanni
authors.forename: P
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: D
authors.initials: D
authors.lastname: Serrano
authors.forename: U
authors.initials: U
authors.lastname: Omodei
authors.forename: C
authors.initials: C
authors.lastname: Varricchio
authors.forename: M
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: M
authors.initials: M
authors.lastname: Lazzeroni
authors.forename: N
authors.initials: N
authors.lastname: Rotmensz
authors.forename: B
authors.initials: B
authors.lastname: Santillo
authors.forename: M
authors.initials: M
authors.lastname: Sideri
authors.forename: E
authors.initials: E
authors.lastname: Cassano
authors.forename: C
authors.initials: C
authors.lastname: Belloni
authors.forename: M
authors.initials: M
authors.lastname: Muraca
authors.forename: N
authors.initials: N
authors.lastname: Segnan
authors.forename: P
authors.initials: P
authors.lastname: Masullo
authors.forename: A
authors.initials: A
authors.lastname: Costa
authors.forename: N
authors.initials: N
authors.lastname: Monti
authors.forename: A
authors.initials: A
authors.lastname: Vella
authors.forename: L
authors.initials: L
authors.lastname: Bisanti
authors.forename: G
authors.initials: G
authors.lastname: D'Aiuto
authors.forename: U
authors.initials: U
authors.lastname: Veronesi
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002979:Climacteric / Q000187:drug effects; D054796:Drug Dosage Calculations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D013629:Tamoxifen / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D013629:Tamoxifen
keywords: breast cancer; chemoprevention; hormone replacement therapy and low dose; tamoxifen