Benefit of anastrozole vs. tamoxifen varied by breast cancer subtype

SAN ANTONIO — The survival benefit postmenopausal patients with breast cancer derive from anastrozole vs. tamoxifen varies considerably by histology, according to an analysis of phase 3 study results presented at the San Antonio Breast Cancer Symposium.

Researchers suggested the finding may help refine adjuvant endocrine treatment decisions.

Several prior studies showed aromatase inhibitors improved outcomes among postmenopausal patients with breast cancer compared with tamoxifen monotherapy. A meta-analysis by Forbes and colleagues, which included data on 11,798 patients included in randomized trials that compared 5 years of tamoxifen vs. a sequence of tamoxifen followed by aromatase inhibitors, showed patients assigned aromatase inhibitors demonstrated a significant reduction in recurrence (RR=0.84; 95% CI, 0.73-0.97). Researchers also observed significantly fewer deaths in the aromatase inhibitor group (RR=0.84; 0.73-0.97).

In the current study, Michael Knauer, PhD, FEBS, senior physician in the department of surgery at the Breast Center in St. Gallen, Switzerland, and colleagues analyzed data from the ABCSG 8 study, which included 3,714 post-menopausal patients (median age, 64 years) with hormone receptor-positive breast cancer who underwent surgery with or without radiotherapy. The cohort included patients with grade 1 and grade 2 disease who did not receive adjuvant chemotherapy.

In the ABCSG 8 study, researchers randomly assigned patients to 5 years of tamoxifen or 2 years of tamoxifen plus 3 years of anastrozole.

Results showed patients assigned to the tamoxifen–anastrozole sequence demonstrated improved DFS (HR=0.91; 95% CI, 0.75-1.1) and OS (HR=0.87; 95% CI, 0.64-1.16), but the differences were not statistically significant.

In their study, Knauer and colleagues evaluated evaluable tissue specimens from 1,478 participants in the ABCSG 8 study to try to identify how molecular alterations affected outcome. Of these tissue specimens, 270 were invasive lobular and 1,085 were invasive ductal.

Results of multivariable analysis showed that, among patients with lobular cancer, the addition of anastrazole was associated with a significant improvement in 3-year OS (HR=0.23; 95% CI, 0.08 vs. 0.68). Researchers did not observe an OS benefit in patients with invasive ductal carcinoma (HR=1.02; 0.7-1.49).

Researchers then stratified results based on luminal A and luminal B subtypes.

In luminal A cancers, anastrazole was associated with a significant reduction in DFS and OS events in ductal cancers (HR for DFS=0.7; 95% CI, 0.53-0.94; HR for OS=0.67; 95% CI, 0.47-0.95), but not in lobular cancers (HR for DFS=1.15; 95% CI, 0.69-1.9; HR for OS=0.76; 95% CI, 0.42-1.39).

In luminal B cancers, anastrazole was associated with a significant reduction in DFS and OS events in lobular cancers (HR for DFS=0.35; 95% CI, 0.16-0.76; HR for OS=0.32; 95% CI, 0.12-0.85) but not in ductal cancers (HR for DFS=0.86; 95% CI, 0.62-1.19; HR for OS=1.09; 95% CI, 0.76-1.56).

“In summary, among all patients with lobular cancer, anastrozole was associated with a significant reduction in OS events compared to tamoxifen,” Knauer said. “However, anastrozole efficacy was strongly depending on histology and intrinsic subtype of breast cancer.”

For more information:

Knauer M. Abstract #S2-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 9-13, 2014; San Antonio.

Disclosure: The researchers report no relevant financial disclosures.