Tamoxifen or AI: Breast Cancer Subtypes Narrow Choice

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

Metzger Filho O, Giobbie-Hurder A, Mallon E, et al
J Clin Oncol. 2015;33:2772-2779

Study Summary

The Breast International Group (BIG) 1-98 study evaluated adjuvant endocrine therapy in postmenopausal women who had hormone receptor-positive early-stage breast cancer. The study participants were randomly assigned to receive either: (1) 5 years of monotherapy with tamoxifen; (2) 5 years of monotherapy with letrozole; (3) 2 years of tamoxifen followed by 3 years of letrozole; or (4) 2 years of letrozole followed by 3 years of tamoxifen.

Patients with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who had centrally reviewed pathology data were included (N=2923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B-like) or low (luminal A-like) proliferative activity by Ki-67 labeling index. Survival analyses were performed.

The median follow-up time was 8.1 years. In multivariable models for disease-free survival, significant interactions between treatment and histology and treatment and subgroup were observed. In the ILC subset, there was a 66% reduction in the hazard of a disease-free survival (DFS) event with letrozole for patients with luminal B subtype and a 50% reduction for patients with luminal A subtype. In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the luminal B subtype, but no difference between treatments was noted for IDC and the luminal A subtype.

The authors concluded that the magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma compared with those with ductal carcinoma.

Viewpoint

This study provides evidence in support of a differential response to hormonal therapies determined by histologic type. Although the authors acknowledge the limitations of their study in assigning biological subtypes (luminal A and luminal B) on the basis of immunohistochemistry criteria, their data are very interesting and show marked variations in clinical benefit for different subgroups of patients exposed to tamoxifen and letrozole.

This information will help us in counseling patients in the clinic: for those with invasive ductal cancers with luminal A tumors, tamoxifen may be just as effective as an aromatase inhibitor. On the other hand, patients with lobular carcinoma seem to derive a meaningful benefit from aromatase inhibitors.

Abstract