The addition of zoledronic acid to anastrozole or tamoxifen improves disease free survival in early stage breast cancer patients, reports the ABCSG-12 study at 62 months. The study, published in The Lancet, revealed the surprising result that although disease free survival remained very similar in the anastrozole and tamoxifen groups, patients taking tamoxifen alone showed superior overall survival.

Historically treatment for early stage breast cancer has focused on direct targeting of cancer cells. More recently studies have suggested that bisphosphonates in addition to their bone targeted effects can modify the microenvironment surrounding cancer cells, making it less conducive to cancer-cell survival and seeding of disease recurrence.

Earlier analysis of the ABCSG -12 (Austrian Breast and Colorectal Cancer Study Group trial-12) study at 48 months' follow-up showed that the addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease free survival. However, because patients had a good prognosis insufficient events occurred to definitively assess the effects of individual treatments on overall survival or to examine subgroup benefits.

In the phase 3 ABCSG-12 trial, led by Michael Gnant from the Medical University of Vienna, 1803 patients were randomised to one of four groups: goserelin plus tamoxifen (n=450); goserelin plus tamoxifen plus zoledronic acid (n=450); goserelin plus anastrozole (n=453); or goserelin plus anastrozole plus zoledronic acid (n=450). The primary endpoint of the trial was to compare disease-free survival for zoledronic acid versus no zoledronic acid and tamoxifen versus anastrozole

The latest results at 62 months show that disease free survival was 92% for patients randomised to zoledronic acid and adjuvant endocrine therapy versus 88% for those receiving endocrine therapy alone. (HR 0.68, p=0.009). While there was no difference in disease free survival between patients on tamoxifen alone versus anastrozole alone (H1.08. p=0.591), the overall survival was found to be worse for those receiving anastrozole alone. Altogether there were 46 deaths in the anastrozole alone group versus 27 in the tamoxifen alone group (HR 1.75, p=0.02).

"On the basis of the results of this study, combination of zoledronic acid with adjuvant endocrine therapy should be considered for premenopausal women with low-or-moderate-risk, early –stage, hormone receptor positive breast cancer," wrote the authors, adding that with longer follow-up the benefits of zoledronic acid have been shown to be independent of the type of endocrine therapy used.

Commenting on the overall survival disadvantage found for patients assigned to the anastrozole group, the authors wrote that one explanation may be that after an initial disease recurrence event, women receiving tamoxifen tended to be switched to an aromatase inhibitor; while women on anastrozole were switched to second line endocrine therapy that was not an aromatase inhibitor.

Reference

M Gnant, B Mlineritsch, H Stoeger, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial, The Lancet, Doi:10.1016/S1470-2045(11)70122-X