Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 537
© 2004 American Society of Clinical Oncology

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Abstract

Molecular effects of anastrozole (A) and tamoxifen (T) alone and combined (C) in the IMPACT trial of neoadjuvant treatment of primary breast cancer

Royal Marsden Hospital, London, United Kingdom

537

Background: Aromatase inhibitors and tamoxifen are key agents for endocrine treatment of postmenopausal breast cancer (BrCa). Understanding of their molecular/biological effects in BrCa is needed for their rational application alone or in combination with novel therapeutics. Methods: 330 postmenopausal patients with invasive BrCa (>/=2cm) were randomised to 12wks neoadjuvant therapy with A, T or C in a placebo-controlled double-blind trial (IMPACT). Biopsies were available from a total of 292 patients pre-treatment and at 2 and 12 wks. Immunohistochemical (IC) studies were performed for Ki67, apoptosis (TUNEL), ER, PgR, EGFR (pre) and HER2 (pre). The growth index (GI: Ki67/apoptosis) was calculated. Plasma estradiol (E2) levels were measured. Results: The %age changes in the biomarkers from baseline are shown in the table. IC results for T and C were similar in all respects. The greater reductions in Ki67 in A vs T have been reported. There were greater reductions in GI for A vs T despite the decreases in apoptosis seen with A and profound differences between the treatments in their effect on PgR. After 2wks the reduction in PgR for A, and the increase in PgR for T were correlated with the fall in Ki67 (p=0.003 and 0.027, respectively). After 12wks there was a significantly lower reduction in Ki67 in HER2+ vs HER2- tumours (geo mean: 73% vs 48%) but no significant difference between the treatment groups. Conclusions: Changes in both Ki67 and GI parallel the greater reduction in relapse rate for A vs T and C in the ATAC adjuvant trial. This suggests short-term biomarker changes may predict for long-term outcome in the adjuvant setting but this needs confirmation. The decrease in apoptosis seen with A suggests that estrogen is not an important survival factor in BrCa cells. Early increases in PgR with T are not associated with a poor antiproliferative effect.

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Abstract presentation from the 2004 ASCO Annual Meeting