Letrozole Superior to Tamoxifen for a Subtype of Breast Cancer

Audrey Andrews

March 2013, Highlights - Hormone Therapy


A comparison of letrozole (Fem­ara) with tamoxifen (Nolva­dex) demonstrated that the former may be superior for the treatment of postmenopausal estrogen receptor (ER)-positive patients who have lobular carcinoma, according to a subanalysis of patients in the phase 3 BIG 1-98 trial. This subanalysis further showed that for the 2 histologic subtypes of breast cancer, luminal B tumors were more responsive to treatment than luminal A tumors.

“The magnitude of benefit of adjuvant letrozole varies by histology and estrogen receptor subgroup. Let­rozole is associated with statistically significant reductions in disease-free survival [DFS] and overall survival [OS] events for both lobular and ductal carcinoma, but the magnitude of benefit is higher for patients diagnosed with lobular carcinoma,” said Otto Metzger-Filho, MD, a research fellow at the Division of Women’s Cancer, Dana-Farber Can­cer Institute, Boston.

The BIG 1-98 trial compared 5 years of treatment with tamoxifen or with letrozole or their sequences in postmenopausal women with ER-positive early breast cancer. The 3660 patients receiving single-agent treatment were divided by invasive lobular or ductal carcinoma. Lobular and ductal tumors were classified into luminal A and luminal B subtypes using a Ki-67 (proliferation index) cutoff of 14%.

Among the 2500 women with ductal carcinoma, 45% had luminal A tumors and 56% had luminal B tumors. Of the 324 women with lobular carcinoma, 73% had luminal A and 27% had luminal B tumors.

Treatment and Histology Affected Outcomes

In the multivariate analysis of DFS, which was adjusted for classic clinicopathologic features, significant interactions were found between treatment and histology. All hazard ratios (HRs) favored letrozole over tamoxifen, but the 0.33 HR for lobular luminal B tumors was the most “impressive,” Dr Metzger-Filho said.

The HRs for other tumor subtypes were 0.49 for lobular luminal A tumors, 0.64 for ductal luminal B tumors, and 0.95 for ductal luminal A tumors. The treatment interactions were highly significant according to histology (ie, ductal carcinoma vs lobular carcinoma; P = .006) and by subtype (ie, luminal A vs luminal B; P = .01).

At 5 years, 89% of patients with lobular tumors who received letrozole showed DFS versus 75% of patients with lobular tumors who received tamoxifen (HR, 0.48); the 8-year DFS was 82% versus 66%, respectively (P = .03).

OS was also significantly favoring letrozole, with an HR of 0.39 for lobular carcinoma and 0.69 for ductal carcinoma. The 8-year OS rates were 88% and 84%, respectively, Dr Metzger-Filho said.

Commenting on these findings, Frankie A. Holmes, MD, oncologist/hematologist at Texas Oncology in Houston, and cochair of the Breast Cancer Research Committee at the US Oncology Network, said she viewed the findings as “practice changing.” She added, “It’s good to see some data, especially for the treatment of an ‘orphan cancer.’” Approximately 10% of patients with breast cancer have a lobular tumor.