Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial
Otto Metzger Filho, Anita Giobbie-Hurder, Elizabeth Mallon, Barry Gusterson, Giuseppe Viale, Eric P Winer, Beat Thürlimann, Richard D Gelber, Marco Colleoni, Bent Ejlertsen, Marc Debled, Karen N Price, Meredith M Regan, Alan S Coates, Aron Goldhirsch, Otto Metzger Filho, Anita Giobbie-Hurder, Elizabeth Mallon, Barry Gusterson, Giuseppe Viale, Eric P Winer, Beat Thürlimann, Richard D Gelber, Marco Colleoni, Bent Ejlertsen, Marc Debled, Karen N Price, Meredith M Regan, Alan S Coates, Aron Goldhirsch
Abstract
Purpose: To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma.
Patients and 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).
Conclusion: The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma.
Trial registration: ClinicalTrials.gov NCT00004205.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.
© 2015 by American Society of Clinical Oncology.
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Source: PubMed