© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 11, 943A-943,
June 7, 2000
© 2000 Oxford University Press
CORRESPONDENCE |
Re: Estimation of Tamoxifen's Efficacy for Preventing the Formation and Growth of Breast Tumors
Affiliation of authors: Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
Correspondence to: Sylvie Ménard, M.D., Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy (e-mail: menard{at}istitutotumori.mi.it).
The recent report by Radmacher and Simon (1) addressed the issue of whether the effect of tamoxifen observed in the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial (BCPT) (2) was "mainly due to prevention of newly forming tumors or to treatment of occult disease." On the basis of analyses in various tumor growth models, those authors (1) concluded that the reduced tumor incidence in the tamoxifen-treated group was probably due to both effects.
By contrast, our recent data (3) obtained with the use of a transgenic mice model of spontaneous development of HER2/neu-positive, estrogen-independent tumors suggest that the protective effect observed in the BCPT is due only to treatment of occult disease. Indeed, in our animal model, early treatment with tamoxifen inhibited the formation of terminal buds in the mammary gland and clearly prevented spontaneous tumors. In contrast, late treatment—when subclinical tumors were already present—had no effect, as expected for the treatment of estrogen-independent tumors.
In the clinical trial, protection only from estrogen receptor-positive tumors was observed, consistent with the dependence on receptor expression of the therapeutic effect of tamoxifen—if tamoxifen acted to prevent new tumors by reducing the number of normal breast epithelial cells at risk of transformation, then both estrogen receptor-positive and estrogen receptor-negative tumors should have been prevented. Moreover, the reduced incidence of breast cancer associated with tamoxifen was not more pronounced in premenopausal women, in whom tamoxifen is likely to inhibit the hormones that govern homeostasis of the normal epithelial cells during the different phases of the menstrual cycle. Therefore, we think that the protective effect observed in the BCPT is due mainly to the treatment of occult disease. However, it might well be that a longer follow-up period in the BCPT will also reveal a reduced incidence of estrogen receptor-negative tumors after long-term treatment with tamoxifen, indicating the prevention of newly formed tumors.
REFERENCES
1
Radmacher MD, Simon R. Estimation of tamoxifen's efficacy for preventing the formation and growth of breast tumors. J Natl Cancer Inst 2000;92:48–53.
2
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371–88.
3
Menard S, Aiello P, Tagliabue E, Rumio C, Lollini PL, Colnaghi MI, et al. Tamoxifen chemoprevention of hormone-independent tumor proto-neu transgenic mice model. Cancer Res 2000;60:273–5.
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