This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dowsett, M. Search for Related Content PubMed PubMed Citation Articles by Dowsett, M.

Preoperative Models to Evaluate Endocrine Strategies for Breast Cancer¹

Academic Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, United Kingdom

There are essentially two approaches to presurgical therapy. The first strategy is one in which the therapy is given to downstage the disease over a period of some 3–4 months. In these circumstances, biological studies can be conducted that can be associated with clinical response. The second strategy involves the institution of medical therapy before surgery with no delay to that surgery. This is essentially incidental and is not given with the aim of having a therapeutic benefit but rather for the biological study of the particular therapeutic approach. In the incidental therapy scenario, we have conducted a number of studies to evaluate the biological effects of raloxifene, idoxifene, fulvestrant (in comparison with tamoxifen), and the aromatase inhibitor 4-hydroxyandrostenedione. Significant reductions in proliferation were noted in all, as was down-regulation of estrogen receptor levels. The changes were most profound in those estrogen receptor-positive tumors that were also progesterone receptor positive, consistent with the greater clinical effect of these therapies in this population. This setting is particularly valuable for treatments in which there is no particular evidence for clinical benefit but in which the therapy is known to be safe. It is possible to evaluate potential resistance mechanisms by associating changes in Ki67 or apoptosis with the expression of the putative determinant of resistance in the short-term presurgical model.

This article has been cited by other articles:

				W. Demark-Wahnefried, S. L George, B. R Switzer, D. C Snyder, J. F Madden, T. J Polascik, M. T Ruffin IV, and R. T Vollmer Overcoming challenges in designing and implementing a phase II randomized controlled trial using a presurgical model to test a dietary intervention in prostate cancer Clinical Trials, June 1, 2008; 5(3): 262 - 272. [Abstract] [PDF]

				M. J. Ellis Neoadjuvant Endocrine Therapy as a Drug Development Strategy Clin. Cancer Res., January 1, 2004; 10(1): 391S - 395S. [Abstract] [Full Text] [PDF]