Journal of the National Cancer Institute Advance Access originally published online on June 27, 2007
JNCI Journal of the National Cancer Institute 2007 99(13):1053-1054; doi:10.1093/jnci/djm020
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Response: Re: Prognostic Value of Ki67 Expression After Short-Term Presurgical Endocrine Therapy for Primary Breast Cancer
Affiliations of authors: Academic Department of Biochemistry (MD), Department of Medicine, Breast Unit (IES), The Royal Marsden Hospital, London SW3 6JJ, UK
Correspondence to: Mitch Dowsett, PhD, Academic Department of Biochemistry, 4th Fl, Wallace Wing, The Royal Marsden Hospital, Fulham Road, London SW3 6 JJ, UK (e-mail: mitch.dowsett{at}icr.ac.uk).
Hrushesky et al. suggest that in our recent report (1), the relationship between recurrence-free survival and Ki67 expression in the excision biopsy after 2 weeks of preoperative treatment with endocrine therapy may not reflect the effect of this treatment but rather some ill-defined biologic effects that result from the trauma associated with the pretreatment needle biopsy. Specifically, they suggest that "the values of such measurements may be associated with either the wounding itself or the interaction of this surgical wounding with endocrine therapy."
We can directly rebut the first of these suggestions on the basis of previous work in which we found that Ki67 values were not statistically significantly different between the pretreatment and excision biopsy samples from subjects in the placebo arms of three short-term (1 or 2 week) preoperative studies (2–4). In these studies, the placebo arms were specifically included to ensure that we would record any effects of wounding on our biomarker measurements.
It is not clear to us how we might directly distinguish between the effect of the endocrine therapy and a hypothetical interaction between such therapy and surgical wounding. However, others (5) have reported that a core biopsy had a measurable impact on the expression of only a few genes, suggesting that the potential for such an interaction is modest. In addition, in the presurgical studies referred to above (2–4), it is notable that the endocrine therapies had no effect on the expression of Ki67 (or other markers) in estrogen receptor (ER)–negative tumors: the absence of an effect on Ki67 expression in the ER-negative subgroup would require that any interaction with trauma also depends on the ER status of the tumor.
Trauma associated with surgery for breast cancer may indeed have effects on long-term outcome, but we find the argument that it explains our 2-week Ki67 observations unconvincing. We maintain our view that the relationship between the 2-week Ki67 value and recurrence-free survival probably relates to a combination of the intrinsic prognostic value of pretreatment Ki67 expression and the change in Ki67 expression associated with estrogen deprivation, effects that are grounded in substantive experimental data from model systems as well as clinical correlations.
REFERENCES
(1) Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A'Hern R, et al. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst (2007) 99:167–70.
(2) DeFriend DJ, Howell A, Nicholson RI, Anderson E, Dowsett M, Mansel RE, et al. Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res (1994) 54:408–14.
(3) Dowsett M, Dixon JM, Horgan K, Salter J, Hills M, Harvey E. Antiproliferative effects of idoxifene in a placebo-controlled trial in primary human breast cancer. Clin Cancer Res (2000) 6:2260–7.
(4) Dowsett M, Bundred NJ, Decensi A, Sainsbury RC, Lu Y, Hills MJ, et al. Effect of raloxifene on breast cancer cell Ki67 and apoptosis: a double-blind, placebo-controlled, randomized clinical trial in postmenopausal patients. Cancer Epidemiol Biomarkers Prev (2001) 10:961–6.
(5) Zanetti-Dällenbach R, Vuaroqueaux V, Wight E, Labuhn M, Singer G, Urban P, et al. Comparison of gene expression profiles in core biopsies and corresponding surgical breast cancer samples. Breast Cancer Res (2006) 8:R51.[CrossRef][Medline]
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J Natl Cancer Inst 2007 99: 1053.
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