Michael Baum, MD, ChM, FRCS, FRCR Professor Emeritus of Surgery Visiting Professor of Medical Humanities, University College London

Edited comments by Professor Baum

Updated data from the ATAC trial: 47-month follow-up

The new ATAC trial data gives me comfort and a sense of vindication that we waited a year before starting to make therapeutic recommendations. Last year I needed persuasion to use adjuvant anastrozole. It was a nice option if tamoxifen could not be tolerated or was contraindicated.

This year, however, with the updated efficacy and safety data, my position has changed. Now my default therapy for postmenopausal women with estrogen receptor-positive tumors is anastrozole, unless contraindicated. We have another year of follow-up in the ATAC trial, and I am impressed by the separation of the curves. The safety update is also comforting. The fracture rate isn’t racing away, the relative risks are stable, and the other safety profile issues continue to strongly favor anastrozole.

Clinical trials of anastrozole in the prevention setting

Some might argue that the reduction of contralateral breast cancers in ATAC looks less promising with the updated data than with the original data — it has gone from about a 60 percent relative reduction to about a 50 percent relative reduction in contralateral breast cancer in the estrogen receptor-positive group. We had the same experience early on with tamoxifen. The extremely dramatic difference seen at three years was reduced over the next few years.

This suggests that these endocrine agents don’t prevent cancer, but rather delay the appearance of cancer. Perhaps anastrozole delays the appearance of breast cancer longer than tamoxifen. I am confident that anastrozole will reduce the risk of estrogen receptor-positive breast cancers — the adjuvant setting will predict the preventive setting. The issue to me is the trade-off and harm/benefit ratio.

Breast conservation rates in the ATAC trial

Gershon Locker presented breast conservation rates in the ATAC trial at the 2002 San Antonio Breast Cancer Symposium. The dramatic finding is that breast conservation is much less common in the United States than in the United Kingdom and other countries. This study shows the beauty of this incredible international database, which allows us to explore cultural differences. It is fascinating that the two countries with the highest rates of breast conservation were France — which is not unexpected — and Brazil. Brazilians are obsessed with the “body beautiful,” but in addition, most Brazilian radiotherapists are trained in France, so we see an interesting cultural issue.

In fairness to the Americans, we should not overinterpret these data. The United Kingdom is a small country in which everyone lives within 100 miles of a radiotherapy center. In contrast, parts of the United States are thousands of miles from a radiotherapy center. Radiation therapy consists of six weeks of treatment. I can sympathize with women for whom it is just impractical to have breastconserving surgery.

Intraoperative radiation therapy

This technology, in theory, could allow us to give all radiotherapy at the time of surgery with a portable machine in a community hospital. We have a neatly packaged mobile electron generator that delivers X-rays at the tip of the probe. You can remove the tumor, apply a spherical applicator to the tumor bed cavity, wrap the tumor bed around this applicator and deliver radiotherapy to the index quadrant. The whole process adds only one-half an hour to the operating time.

This technique gives the biological equivalent dose of 50 Gy to the tumor bed. The geometry is better than conventional radiotherapy. Traditional conformal radiotherapy conforms to an uncertain shape. With this method, we conform the cavity to the radiotherapy source, so I think we'll do better than with conventional external beam radiation therapy.

We did a Phase II study in 40 patients, and although I distrust Phase II studies, it appears extremely safe and has excellent cosmetic results. Only one woman developed ulcerated skin, which ultimately healed. In this series, over the maximum four or five years of follow-up, we have not had a single local recurrence.

We have opened an exciting trial, randomizing patients to conventional postoperative radiotherapy versus intraoperative radiotherapy. We’re hoping to enroll 2,000 patients in the study, so we need to “spread our wings.” There is enormous interest, and we have started randomization. We have groups in Australia, North America and Germany.

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