Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence-free survival.
Publication Date
2005-01Author
Dowsett, M
Smith, IE
Ebbs, SR
Dixon, JM
Skene, A
Griffith, C
Boeddinghaus, I
Salter, J
Detre, S
Hills, M
Ashley, S
Francis, S
Walsh, G
IMPACT Trialists
Type
Journal Article
Metadata
Show full item recordAbstract
<h4>Purpose</h4>Neoadjuvant (preoperative) therapy for breast cancer may allow for the development of intermediate markers of treatment benefit, thereby circumventing the need for efficacy trials of adjuvant therapy, which require much larger patient numbers and longer follow-up. The aim of this study--as part of the Immediate Preoperative "Arimidex" (anastrozole), Tamoxifen, or Arimidex Combined with Tamoxifen (IMPACT) trial (n = 330)--was to test the hypotheses that changes in Ki-67 after 2 weeks and/or 12 weeks: (i) differed between treatments, (ii) predicted clinical tumor response, and/or (iii) may predict long-term outcome differences between treatments in adjuvant therapy.<h4>Experimental design</h4>The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared these same agents in the adjuvant setting. Biomarkers were measured in biopsy specimens taken before and after 2 and 12 weeks of treatment.<h4>Results</h4>Suppression of the proliferation marker Ki-67 after 2 and 12 weeks was significantly greater with anastrozole than with tamoxifen (P = 0.004 and P < 0.001) but was similar between tamoxifen and the combination (P = 0.600 and P = 0.912). This result closely parallels that seen for the relative recurrence-free survival with the treatments after a median follow-up of 31 months in the ATAC trial in 9,366 patients. Against expectations, apoptosis was not increased in any of the treatment arms.<h4>Conclusions</h4>The data indicate that short-term changes in proliferation in the neoadjuvant setting may be able to predict outcome during adjuvant use of the same treatments. If this can be confirmed, these findings could lead to a profound change in approaches to drug development in breast cancer. The data indicate that estrogen is not an important survival factor for human breast cancer cells.
Subject
IMPACT Trialists
Humans
Breast Neoplasms
Neoplasm Recurrence, Local
Tamoxifen
Nitriles
Triazoles
Ki-67 Antigen
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Treatment Outcome
Chemotherapy, Adjuvant
Neoadjuvant Therapy
Survival Rate
Follow-Up Studies
Double-Blind Method
Apoptosis
Cell Proliferation
Aged
Female
Anastrozole
Research team
Medicine (RMH Smith Cunningham)
Endocrinology
Language
eng
License start date
2005-01
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2005, 11 (2 Pt 2), pp. 951s - 958s