© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 12, 917-918,
June 18, 2003
© 2003 Oxford University Press
CORRESPONDENCE |
Re: Italian Randomized Trial Among Women With Hysterectomy: Tamoxifen and Hormone-Dependent Breast Cancer in High-Risk Women
Affiliations of Authors: S. Ménard, P. Casalini, E. Tagliabue, S. M. Pupa, A. Balsari, Molecular Targeting Unit, Dept. of Experimental Oncology, Istituto Nazionale Tumori; and Institute of Pathology, University of Milan, 20133 Milan, Italy.
Correspondence to: Sylvie Ménard, Ph.D., Molecular Targeting Unit, Dept. of Experimental Oncology, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy (e-mail: sylvie.menard{at}istitutotumori.mi.it).
In their recent paper, Veronesi et al. (1) reported that women, divided into two groups according to their risk of developing breast carcinomas, respond differently to the preventive effect of tamoxifen. In addition to the impressive reduction of tumors obtained with tamoxifen among women in the high-risk group, the study gives important epidemiologic information: 1) hormone replacement therapy (HRT) appears to be a risk factor for breast carcinoma only for women at high risk, suggesting that an early hormone exposure (early menarche, nulliparity, late age at first pregnancy, intact ovarian function) predisposes these women to an additional risk resulting from subsequent hormone exposure. By contrast, among women at low risk for breast carcinoma, HRT did not seem to be associated with a substantially increased risk. 2) For most of the risk factors analyzed in these hysterectomized patients, Veronesi et al. (1) report odds ratios that are notably higher than those reported in the general population (2). If not a result of the relatively low number of patients analyzed, the impact of hormone exposure might be a result of a particularly low risk among this hysterectomized group. Accordingly, considering all the tumors, the frequency of estrogen receptor (ER)-negative tumors is higher than expected, suggesting a baseline protection of ER-positive tumors. Moreover, in contrast with a previous report indicating a prevalence of ER-positive tumors in high-risk patients (3), the study by Veronesi et al. (1) showed that the frequency of ER-positive tumors is similar among the low- and high-risk subgroups.
The finding that tamoxifen does not protect women at low risk from ER-positive tumors indicates that other parameters negatively regulate hormone responsiveness in this subgroup of women. Overexpression of the HER2 oncogene has been associated with hormone independency (4). We recently showed that the frequency of HER2-overexpressing breast carcinomas changes in patients according to their hormonal risk category, suggesting that HER2-overexpressing breast carcinomas are not protected by hormone-related factors (5). An additional analysis of this series of about 2000 primary carcinomas indicated that, in patients identified at low risk (i.e., those who have more than three children and late menarche), 42% of tumors were HER2-positive compared with 21% in patients identified at high risk (less than three children and early menarche). It would be relevant to know the distribution of HER2-positive tumors in the various groups in the prevention trial by Veronesi et al. (1). In fact, the lack of efficacy of tamoxifen among women in the low-risk group might be related to a higher frequency of HER2-overexpressing tumors, which are less sensitive to hormones. Furthermore, inhibition of incidence of a breast cancer subset (i.e., hormone-responsive) by the treatment might counterbalance an increase of incidence of another subset (i.e., the HER2-positive), giving an overall null effect of the treatment. A detrimental effect of tamoxifen observed in an experimental model of HER2 transgenic mice was the result of an effect on occult tumors (6); however, tamoxifen administration before tumor onset was found to protect against HER2-positive tumors. Thus, the information regarding HER2 status of the tumors from the trial by Veronesi et al. (1) should help in understanding the action of tamoxifen.
REFERENCES
1 Veronesi U, Maisonneuve P, Rotmensz N, Costa A, Sacchini V, Travaglini R, et al. Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women. J Natl Cancer Inst 2003;95:160–5.
2 Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993;15:36–47.
3 Huang WY, Newman B, Millikan RC, Schell MJ, Hulka BS, Moorman PG. Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status. Am J Epidemiol 2000;151:703–14.
4 Houston SJ, Plunkett TA, Barnes DM, Smith P, Rubens RD, Miles DW. Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer. Br J Cancer 1999;79:1220–6.[CrossRef][ISI][Medline]
5 Balsari A, Casalini P, Bufalino R, Berrino F, Ménard, S. Role of hormonal risk factors in her2-positive breast carcinomas. Br J Cancer 2003;88:1032–4.[CrossRef][ISI][Medline]
6 Ménard S, Aiello P, Tagliabue E, Rumio C, Lollini PL, Colnaghi MI, et al. Tamoxifen chemoprevention of a hormone-independent tumor in the proto-neu-transgenic mice model. Cancer Res 2000;60:273–5.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||