title: Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.
abstract: OBJECTIVE
  To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma.
  
  
  METHODS
  Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling.
  
  
  RESULTS
  The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20).
  
  
  CONCLUSIONS
  The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma.
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia. otto_metzger@dfci.harvard.edu.
authors.forename: Otto
authors.initials: O
authors.lastname: Metzger Filho
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mallon
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Barry
authors.initials: B
authors.lastname: Gusterson
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Beat
authors.initials: B
authors.lastname: Thürlimann
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Marc
authors.initials: M
authors.lastname: Debled
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.affiliation: Otto Metzger Filho, Anita Giobbie-Hurder, and Eric P. Winer, Dana-Farber Cancer Institute; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Karen N. Price, Frontier Science and Technology Research, Boston, MA; Elizabeth Mallon, Southern General Hospital; Barry Gusterson, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; Giuseppe Viale, European Institute of Oncology and University of Milan; Marco Colleoni and Aron Goldhirsch, European Institute of Oncology, Milan, Italy; Beat Thürlimann, Kantonsspital, St. Gallen, and Swiss Group for Clinical Cancer Research, Bern, Switzerland; Bent Ejlertsen, Rigshospitalet, Copenhagen, Denmark; Marc Debled, Institut Bergoniié, Bordeaux, France; and Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia.
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000188:drug therapy*; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014230:Triazoles; C508053:ERBB2 protein, human