Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 25 Pg. 2772-9 (Sep 01 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26215945 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Antineoplastic Agents, Hormonal
• Aromatase Inhibitors
• Biomarkers, Tumor
• Ki-67 Antigen
• Nitriles
• Triazoles
• Tamoxifen
• Letrozole
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Antineoplastic Agents, Hormonal (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Aromatase Inhibitors (therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (drug therapy)
• Carcinoma, Ductal, Breast (chemistry, drug therapy)
• Carcinoma, Lobular (chemistry, drug therapy)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Female
• Humans
• Ki-67 Antigen (analysis)
• Letrozole
• Middle Aged
• Nitriles (therapeutic use)
• Receptor, ErbB-2 (analysis)
• Tamoxifen (therapeutic use)
• Treatment Outcome
• Triazoles (therapeutic use)