Journal of the National Cancer Institute Advance Access originally published online on October 30, 2007
JNCI Journal of the National Cancer Institute 2007 99(21):1644-1645; doi:10.1093/jnci/djm177
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Responses: Re: Treatment of Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer Xenografts With Multiagent Human Epidermal Growth Factor Receptor-Targeted Therapy
Affiliations of authors: European Institute of Oncology, Milan, Italy (UV, BB); Ospedale Galliera, Genoa, Italy (AD)
Correspondence to: Umberto Veronesi, MD, European Institute of Oncology, via Ripamonti 435, Milan, Italy (e-mail: umberto.veronesi{at}ieo.it).
Ferretti et al. comment on our recent article on the late results of the Italian Tamoxifen Prevention Trial (1). They discuss the mixed findings of the effects of tamoxifen in users of hormone replacement therapy (HRT) (mostly unopposed estrogen replacement therapy, because all women had had hysterectomy) and compare our results with those of the International Breast Cancer Intervention Study (IBIS-I) (2) and Royal Marsden (3) chemoprevention trials. In particular, they point out the following results. We observed (1) a beneficial trend in women who took HRT at baseline. The IBIS-I trial (2) found no advantage with tamoxifen among current users but a statistically significant trend toward reduced risk reduction among past users. The Marsden trial (3) found no positive impact with the combination of HRT and tamoxifen.
Data on tamoxifen efficacy in HRT users, which were confirmed in our follow-up (1), admittedly were derived from unplanned subset analyses. However, results of tamoxifen among women at high risk for hormone-related cancer, including HRT users, provided the rationale for a definitive trial, which is underway (4). In the meantime, the safety of the combination of tamoxifen and HRT is becoming evident. Preliminary data on the HRT Opposed to Low-Dose Tamoxifen study (5) show a very low rate of adverse events, particularly cardiovascular events, and results from a previous phase II study (6) in a similar population show that low doses of tamoxifen associated with HRT favorably modulate biomarkers of breast carcinogenesis and cardiovascular risk, with no increase of endometrial proliferation and menopausal symptoms. It is important to note that, in both studies (4,6), more than half of the subjects used transdermal rather than oral estrogens, whereas most HRT compounds were administered orally in the IBIS-I and Marsden trials (2,3). Given the different metabolic and endocrine effects between the two routes of HRT administration (7), this observation may be an important factor in explaining the differences between the studies.
Thus, although it is presently unclear whether the combination of HRT and tamoxifen retains the benefits of either agent alone, our data indicate that the combination is safe.
REFERENCES
(1) Veronesi U, Maisonneuve P, Rotmensz N, Bonanni B, Boyle P, Viale G, et al. Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention trial among women with hysterectomy. In: J Natl Cancer Inst (2007) 99:727–37.
(2) Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H, Holli K, et al. Long-term results of tamoxifen prophylaxis for breast cancer—96 month follow-up of the randomized IBIS-I study. J Natl Cancer Inst (2007) 99:272–82.
(3) Powles TJ, Ashley S, Tidy A, Smith IE, Dowsett M. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst (2007) 99:283–90.
(4) Decensi A, Galli A, Veronesi U. HRT opposed to low-dose tamoxifen (HOT study): rationale and design. Recent Results Cancer Res (2003) 163:104–11.[Medline]
(5) Bonanni B, Santillo B, Serrano D, Rotmensz N, Muraca M, Vella A, et al. The hormone replacement therapy opposed to low dose tamoxifen (HOT) study: safety data from an ongoing phase III trial. J Clin Oncol (2007) 25(Suppl). Abstract 1514.
(6) Decensi A, Gandini S, Serrano D, Cazzaniga M, Pizzamiglio M, Maffini F, et al. Randomized dose-ranging trial of tamoxifen at low doses in hormone replacement therapy users. J Clin Oncol (2007) 25:4201–9.
(7) Scarabin PY, Oger E, Plu-Bureau G. EStrogen and THromboEmbolism Risk Study Group. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet (2003) 362:428–32.[CrossRef][Web of Science][Medline]
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J Natl Cancer Inst 2007 99: 1644.
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