He noted that although tamoxifen is a very effective drug, it has side
effects. "The goal of research in this area is to improve that side
effects profile." He called anastrozole "a drug that has better
anticancer activity with fewer side effects than tamoxifen. Now, 17 out of 100
patients who, in spite of tamoxifen therapy, would have recurred will remain
disease free because they got anastrozole."
Anastrozole works by reducing circulating estrogen in postmenopausal women.
Selective inhibition of aromatase by anastrozole suppresses the formation of estrogen and hence reduces the
stimulatory effect of estrogen on breast tissue. Tamoxifen selectively blocks
estrogen from stimulating breast cancer cells by binding to the estrogen
In the ATAC study, anastrozole produced significantly fewer side effects
than tamoxifen, including fewer cases of endometrial cancer, fewer
thromboembolic events, less vaginal bleeding and discharge, and fewer
Deep-vein thrombosis was reported in 1.7% of tamoxifen patients, compared
with 1% of anastrozole patients; endometrial cancer occurred in 0.5% and 0.1%,
respectively; and vaginal bleeding occurred in 8.1% and 4.5%, respectively. Hot
flashes and weight gain were also slightly more common with tamoxifen.
More Bone Fractures
Anastrozole was associated with significantly more bone fractures (primarily
of the wrist) and musculoskeletal pain. The 2.1% absolute increase in fractures
(5.8% vs 3.7% for tamoxifen) was of particular concern to several investigators
who commented on the findings.
Paul Goss, MD, of Princess Margaret Hospital, Toronto, for example,
presented a poster (abstract 132) showing that another aromatase inhibitor,
exemestane (Aromasin), was not associated with bone loss in a randomized
controlled study in ovariectomized rats.
Dr. Goss commented about the ATAC results, "This is very real and
compelling clinical data, not just a measurement of bone mineral density. A 2%
increase in fractures is a serious toxicity."