title: Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17.
abstract: OBJECTIVE
  Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR-than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status.
  
  
  METHODS
  Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy.
  
  
  RESULTS
  The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI, 0.63 to 2.34) in ER+/PgR-tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR-subgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09).
  
  
  CONCLUSIONS
  These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.
authors: Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA. pgoss@partners.org
authors: Paul E
authors: PE
authors: Goss
authors: James N
authors: JN
authors: Ingle
authors: Silvana
authors: S
authors: Martino
authors: Nicholas J
authors: NJ
authors: Robert
authors: Hyman B
authors: HB
authors: Muss
authors: Martine J
authors: MJ
authors: Piccart
authors: Monica
authors: M
authors: Castiglione
authors: Dongsheng
authors: D
authors: Tu
authors: Lois E
authors: LE
authors: Shepherd
authors: Kathleen I
authors: KI
authors: Pritchard
authors: Robert B
authors: RB
authors: Livingston
authors: Nancy E
authors: NE
authors: Davidson
authors: Larry
authors: L
authors: Norton
authors: Edith A
authors: EA
authors: Perez
authors: Jeffrey S
authors: JS
authors: Abrams
authors: David A
authors: DA
authors: Cameron
authors: Michael J
authors: MJ
authors: Palmer
authors: Joseph L
authors: JL
authors: Pater
mesh_terms: D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002170:Canada / Q000453:epidemiology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D010919:Placebos; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D009570:Nitriles; D010919:Placebos; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole