Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer

Mitch Dowsett, Ian E. Smith, Steve R. Ebbs, J. Michael Dixon, Anthony Skene, Clive Griffith, Irene Boeddinghaus, Janine Salter, Simone Detre, Margaret Hills, Susan Ashley, Stephen Francis, Geraldine Walsh, Roger A'Hern, Carlos Arteaga, Aman Buzdar, James Ingle, Steven Come, Myles Brown

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81 Scopus citations

Abstract

The study of changes in proliferation as a marker of treatment benefit during presurgical endocrine treatment of breast cancer has become increasingly popular, particularly using the nuclear marker Ki67, and holds the potential for prioritizing new treatments for full clinical development. There are weakly significant relationships between Ki67 change and clinical response that differ according to data handling. In the neoadjuvant Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen trial, suppression of Ki67 at both 2 and 12 weeks was greater with the aromatase inhibitor anastrozole than with either tamoxifen or the combination of anastrozole and tamoxifen. We report here that absolute values of Ki67 after 2 weeks were also significantly lower with anastrozole than with tamoxifen and the combination. This indicates that it may be possible to make such comparisons using surgical samples only. We argue that these changes in proliferation and concurrent changes in apoptosis may be expected to be more predictive of adjuvant benefit from endocrine therapy than clinical response.

Original languageEnglish (US)
Pages (from-to)1024s-1030s
JournalClinical Cancer Research
Volume12
Issue number3 II
DOIs
StatePublished - Feb 1 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dowsett, M., Smith, I. E., Ebbs, S. R., Dixon, J. M., Skene, A., Griffith, C., Boeddinghaus, I., Salter, J., Detre, S., Hills, M., Ashley, S., Francis, S., Walsh, G., A'Hern, R., Arteaga, C., Buzdar, A., Ingle, J., Come, S., & Brown, M. (2006). Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer. Clinical Cancer Research, 12(3 II), 1024s-1030s. https://doi.org/10.1158/1078-0432.CCR-05-2127