COPENHAGEN, DenmarkThe risk and incidence of bone
fractures associated with the use of the aromatase inhibitor anastrozole (Arimidex)
for treatment of early breast cancer in postmenopausal women appears to
stabilize after peaking at 2 years, easing some of the major concerns about the
Anthony Howell, MD, chairman of the ATAC (Arimidex,
Tamoxifen Alone or in Combination) steering committee and professor of
oncology, University of Manchester, UK, presented the data at the European
Cancer Conference (ECCO 12) (abstract 676).
ATAC, the world’s largest ongoing multicenter,
double-blind study of breast cancer treatment, compares the efficacy and safety
of anastrozole 1 mg once daily with tamoxifen (Nolvadex) 20 mg once daily, as
adjuvant therapy for postmenopausal women with hormone-receptor-positive early
breast cancer. The trial included woman who were eligible for, but had not
received, prior adjuvant hormonal therapy. Patients were randomized to receive
anastrozole (n = 3,125), tamoxifen (n = 3,116), or anastrozole and tamoxifen
combined (n = 3,125).
Previous reports from ATAC showed that over a median
follow-up of 33 months, anastrozole increased disease-free survival by 19% and
reduced recurrence by an absolute difference of 1.8%, compared with tamoxifen.
The incidence of new tumors in the opposite breast was also reduced by more
than 58%. Data updated when the median follow-up reached 47 months showed that
the gap in absolute difference in recurrence had widened to 2.6% in favor of
"The reduction in disease occurrence and the favorable
safety profile, especially the thromboembolic events and the absence of a tumor
agonist effect sometimes seen with tamoxifen, are reason why the overall risk
benefit for anastrozole for women with early breast cancer remains
positive," Dr. Howell said.
Nonetheless, physicians need to be cautious in their use of
anastrozole. "We should still wait for the overall survival data next
year," Dr. Howell said.
Bone Fracture Data
This tempered enthusiasm is caused by the fact that
anastrozole has been associated with an increased risk of bone fractures.
Because of the increased estrogen deprivation with anastrozole, it is not
unexpected that women on this drug might have a higher risk of fractures than
those on tamoxifen, a drug known to have a mildly positive effect on bone
Although the ATAC study confirmed that there are slightly
more fractures in women treated with anastrozole (range 0.93 to 1,57), than
with tamoxifen (range 0.58 to 1.37), the difference is not statistically
significant, Dr. Howell said, and the overall benefit-to-risk in early breast
cancer remains unchanged, favoring anastrozole.
In this newest analysis, the ATAC researchers looked at data
on fracture incidence at 6-month intervals for up to 48 months of treatment.
Said Dr. Howell, "We found that at the first analysis,
after 31 months median duration of treatment, the incidence of fractures was
5.9% in anastrozole patients, compared with 3.7% in tamoxifen patientsnearly
60% greater. But, when the data were updated at 37 months, the incidence was
7.1% vs 4.4%, so still around a 60% difference. The risk had not
In fact, he said, the 6 monthly fracture rates for anastrozole reached a
plateau after 24 months, with the maximum difference between the two treatments
being seen at 18 and 24 months. "By the last follow-up at 48 months, the
increase in risk was down to about one third higher for anastrozole," he
said. There were similar patterns for fractures of the hip, spine, and wrist.