Neoadjuvant Anastrozole Reduces Need for Mastectomy

Jane Salodof MacNeil

December 03, 2003

Dec. 3, 2003 (San Antonio) — Neoadjuvant therapy with anastrozole (Arimidex) was twice as effective in downstaging tumors originally recommended for mastectomy in a clinical trial comparing the aromatase inhibitor to tamoxifen and a combination of tamoxifen and anastrozole.

After three months of anastrozole treatment, 45% of the women in the study with large breast cancers were revaluated and referred for breast-conserving treatment. Only 22.2% of women were similarly downstaged in the tamoxifen group, and 26.2% in the combination group.

"In a nutshell, this is neoadjuvant attack," announced Ian Smith, MD, from Royal Marsden Hospital in London, U.K., presenting results from the Immediate Preoperative Arimidex Compared to Tamoxifen (IMPACT) trial here today during the opening session of the 26th Annual San Antonio Breast Cancer Symposium.

Conducted at 16 centers in the U.K. and Germany, the trial enrolled 330 mostly elderly, postmenopausal women with invasive operable breast tumor defined as 2 cm or larger. At baseline, surgeon's recommendations were recorded for 220 patients, of whom 124 (56%) had been recommended for mastectomy.

The 330 women were randomized so that 113 received anastrozole, 108 received tamoxifen, and 109 received combination therapy. Relative risk and objective clinical tumor response (OR) were similar for the three groups.

Anastrozole was markedly superior in women with HER2-positive tumors, according to Dr. Smith. In the anastrozole group, 7 (58%) of 12 patients were downstaged to breast-conserving surgery. Of those receiving tamoxifen, 2 (22%) of 9 HER2-positive participants were downstaged, as well as 31% of those receiving both agents.

Although dramatic, the comparison did not reach statistical significance because of the small number of HER2-positive women in the study. Of 239 women who were assessable for HER2 expression, Dr. Smith said 34 patients (14.2%) had overexpression.

Nonetheless, he told Medscape that he believes the results are ready for clinical application because they confirm the superiority of anastrozole over tamoxifen, as had previously been reported in the 9,366-patient Anastrozole Tamoxifen Alone or in Combination (ATAC) trial in the adjuvant setting.

"In patients with large breast cancers requiring breast mastectomy, I think it's better to use anastrozole than tamoxifen to downstage," he said, "and in patients overexpressing HER2. I think there's enough strong evidence from [our study] and the letrozole [Femara] trial that aromatase inhibitors are superior."

In a companion presentation from the IMPACT trial, Mitchell Dowsett, PhD, also from Royal Marsden, reported that preliminary analysis of biological changes in the proliferation marker Ki67 suggested it might be used to predict long-term response to treatment. He cautioned that the data only apply to groups of patients, not individuals, but suggested Ki67 might prove useful in endocrine trials.

Session moderator Richard Ellege, MD, from Baylor School of Medicine and Methodist Hospital in Houston, Texas, commented afterward that he thought the possibility of Ki67 being used to assess response was an interesting finding. The major contribution of the IMPACT study was that it confirmed results from ATAC and studies of letrozole, another aromatase inhibitor, he said.

"The IMPACT trial confirms other studies, letrozole studies, that you can avoid mastectomies in some patients by giving them neoadjuvant aromatase inhibitors," Dr. Ellege said.

The study received support from AstraZeneca, the maker of anastrozole.

26th Annual SABCS: Abstracts 1 and 2. Presented Dec. 3, 2003.

Reviewed by Gary D. Vogin, MD

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