Originally published as JCO Early Release 10.1200/JCO.2005.07.559 on March 14 2005

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Biomarker Changes During Neoadjuvant Anastrozole, Tamoxifen, or the Combination: Influence of Hormonal Status and HER-2 in Breast Cancer—A Study from the IMPACT Trialists

Mitch Dowsett, Steve R. Ebbs, J. Michael Dixon, Anthony Skene, Clive Griffith, Irene Boeddinghaus, Janine Salter, Simone Detre, Margaret Hills, Susan Ashley, Stephen Francis, Geraldine Walsh, Ian E. Smith

From the Academic Department of Biochemistry and the Breast Unit, Royal Marsden Hospital, London; Mayday University Hospital, Croydon, Surrey; Edinburgh Breast Unit, Edinburgh; Royal Bournemouth Hospital, Bournemouth, Dorset; Royal Victoria Infirmary, Newcastle Upon Tyne, Tyne and Wear; and AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom

Address reprints requests to Mitch Dowsett, MD, Academic Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, United Kingdom; e-mail: mitch.dowsett{at}icr.ac.uk.

PURPOSE: To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy.

PATIENTS AND METHODS: The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment.

RESULTS: A decrease in the proliferation marker Ki67 occurred in the majority of patients: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks.

CONCLUSION: These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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