Benefit of Adjuvant Letrozole vs Tamoxifen Is Greater in Lobular Than in Ductal Breast Cancer
In a BIG 1-98 trial analysis reported in the Journal of Clinical Oncology, Metzger Filho et al found that the benefit of adjuvant letrozole vs tamoxifen was greater in patients with lobular than ductal breast carcinoma.
Study Details
In the BIG 1-98 trial, postmenopausal women with hormone receptor–positive early-stage breast cancer were randomized to receive 5 years of letrozole or tamoxifen as monotherapy or in sequence. The 8.1-year follow-up of the trial showed a reduction in breast cancer recurrence and mortality for letrozole vs tamoxifen monotherapy.
The current analysis included 2,923 HER2-negative patients with invasive ductal carcinoma or classic invasive lobular carcinoma who had centrally reviewed pathology data and received letrozole (n =1,452) or tamoxifen monotherapy (n = 1,471). HER2-positive patients were excluded from the analysis. Invasive ductal carcinoma and invasive lobular carcinoma were classified as hormone receptor–positive with high (luminal B–like) or low (luminal A–like) proliferative activity by Ki-67 labeling index.
Subgroup Benefits
In multivariable models for disease-free survival, significant interactions were found between treatment and histology (invasive lobular carcinoma or invasive ductal carcinoma, P = .006) and treatment and subgroup (luminal B–like or luminal A–like, P = .01).
Among patients with invasive lobular carcinoma, letrozole treatment was associated with a significantly reduced risk of disease-free survival events in both patients with luminal B–like (hazard ratio [HR] = 0.34, 95% confidence interval [CI] = 0.21–0.55) and luminal A–like subtypes (HR = 0.50, 95% CI = 0.32–0.78). Among patients with invasive ductal carcinoma, letrozole was associated with a significant reduction in risk for a disease-free survival event in patients with luminal B–like subtype (HR = 0.65, 95% CI = 0.53–0.79) but not in those with the luminal A–like subtype (HR = 0.95, 95% CI = 0.76–1.20).
The investigators concluded: “The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma…. [A]lthough the current data suggest a greater benefit of adjuvant letrozole than tamoxifen for patients diagnosed with [invasive lobular carcinoma], subsequent validation in larger data sets is necessary before implementing a routine clinical recommendation of [aromatase inhibitors] for patients diagnosed with [invasive lobular carcinoma].”
Otto Metzger Filho, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article. Dr. Metzger Filho and Anita Giobbie-Hurder, MS, contributed equally to the work.
The study was supported by Novartis (sponsorship of the BIG 1-98 trial) and coordinated by the International Breast Cancer Study Group (IBCSG). The IBCSG was supported by the Swedish Cancer Society, Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, U.S. National Institutes of Health, Cancer Research Switzerland/Oncosuisse, and Foundation for Clinical Cancer Research of Eastern Switzerland. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
