Gershon Locker, MD
Kellogg Scanlon Chair of Oncology, Evanston Northwestern Healthcare Professor of Medicine, Northwestern University Feinberg School of Medicine

Edited comments by Dr Locker

Implications of the updated ATAC trial data

I saw the initial data a month before it was initially presented in San Antonio in 2001, and I was literally blown away. No one expected the trial to turn so positive so quickly. My takeaway, even after the initial data, was that a newly diagnosed, postmenopausal woman with hormone receptor-positive breast cancer should be offered anastrozole, at least as an alternative, if not the preferred treatment. In the year since, and with the updated data, my feelings have not changed at all. The 47-month follow-up was very reassuring, because the curves continue to separate. I would have been surprised if they didn’t.

Everyone is waiting for survival data, but it is important to remember the disease-free survival is remarkably good — in the 88 to 90 percent range — in this group of women. Therefore, it will be a while before we can evaluate survival. However, it should be emphasized that in every adjuvant trial demonstrating a disease-free survival difference, a survival difference has eventually appeared.

I tell my patients that these data are preliminary, albeit with very strong statistical support for efficacy. Approximately 75 percent of my postmenopausal, ER-positive patients receive anastrozole instead of tamoxifen.

Anastrozole is a better hormonal adjuvant treatment than tamoxifen for ERpositive postmenopausal women, but there will always be a subset of women for whom tamoxifen may be preferred. For example, tamoxifen may be better for women with osteoporosis coming in with the diagnosis of breast cancer, particularly those already on bisphosphonates or calcitonin. In general, I believe anastrozole is the preferred treatment.

Risks and side effects of tamoxifen versus anastrozole

The biggest problem with tamoxifen is not the risk of thromboembolism or uterine cancer, but managing uterine bleeding. Any woman who has uterine bleeding on tamoxifen goes through a panoply of tests, which causes a great deal of anxiety. A large percentage of women, sometime during their five years of therapy, undergo a gynecologic procedure. This is what’s really unacceptable about tamoxifen. We over-investigate some of these symptoms. This may be due to our medical-legal milieu, but it contributes to a miserable lifestyle and a lot of anxiety for women on tamoxifen in the adjuvant and preventative settings.

Rates of breast-conserving surgery in the ATAC trial

There was a striking difference in breast conservation rates in the ATAC trial between the two largest countries accruing patients — the United Kingdom and the United States. In a large, multivariate analysis taking every other factor into account, being an American woman increases your likelihood of having a mastectomy by 44 percent, compared to being a British woman. There is something about American patients or surgeons that seems to favor mastectomy compared to what is done in the United Kingdom.

One potential explanation is that, although we have guidelines set by the National Cancer Institute, American medicine is still individualized — the surgeon and patient make the final decision. Guidelines tend not to be as significant a factor in decision-making. Another issue is our American view that more is better. We have data, however, that this is not true in the mastectomy versus lumpectomy decision. Psychological factors also play a role for some women, in whom the thought of having a “cancerous breast,” even if the cancer is removed, is not acceptable. It is also conceivable that geography is a significant issue for some women. In England, no woman is more than 50 or 60 miles from a major city. A woman in Montana may be hundreds of miles from a center where she can receive radiation therapy.

We need to better educate surgeons and patients that there is no survival difference between these two methods of treating early-stage breast cancer, and the preferred approach, when possible, is lumpectomy and radiation, for aesthetic, psychological and a number of other reasons.

Clinical trials of aromatase inhibitors for risk reduction

Aromatase inhibitors have potential as chemopreventive agents. The data from ATAC show that anastrozole is more effective in preventing contralateral breast cancers than tamoxifen. It’s a natural transition to move anastrozole into the preventative research setting. I would have preferred that the European IBIS-II prevention trial compare anastrozole to tamoxifen rather than to placebo. Because it doesn’t, this trial would never fly in the United States, but I’m glad the NSABP-B-35 DCIS trial is making the correct comparison of anastrozole versus tamoxifen.

Select publications

Home · Search