Vitamin A analogue for breast cancer prevention: a grade of F or incomplete?

Field: Medicine (Health Sciences)

CORRESPONDENCE Re: Vitamin A Analogue for Breast Cancer Prevention: a Grade of For lnc.omplete? We were annoyed by the disparaging title given to the editorial written by S. Piantadosi ( J) on our breast cancer pre- vention trial with fenretinide, which was published in the November 3 issue of the Journal (2). First, we feel that the title is not consistent with the editorial content itself (who gives an F grade to a well designed and conducted study ?). In ad- dition, the title is in sharp contradiction with Journal policy to publish only ar- ticles of major importance. Our disap- pointment was increased after learning that, as a result of this title, several me- dia outlets have dismissed our study as being one of poor quality. In the current publicity-dominated era. the choice of this title is at best unscrupulous, if not dictated by reasons that have l!ttle to do with science. It is a shame that the irresistible temptation of adding a sensationalist title has overcome a more reasonable re- view of our study, while we think we have honestly addressed the limitations of our work in the paper. Contrary to Dr. Piantadosi's doubts, we h ad clearly stated in the article that, among the doz.en possible interactions, we tested only the one between fenretinide treat- ment and menopausal status because this interaction has strong biologic sup- port. This support came not only fr~m our previous observations that plasma insulin-like growth factor-I (IGF-n lev- els behaved with the same pattern fol- lowing fenretinide treatment [refs. (27) and (28) of our paper], but also from the well-established notion that premeno- pausal and postmenopausal breast can- cer are different diseases that receive different treatments and have different risk factors, some of which, like body mass index, interapt in a qualitative manner with menopausal status [refs. (39-41) of our paper]. Since we believe that biologic plau- sibility should dnve statistics and not vice versa, we feel that leaving this in- teraction untested would have missed 274 CORRESPONDENCE some very important infonnation. It is argued that our study was not powered to test such an interaction. Consistently, we have not recommended treating pre- menopausal women with fenretinide but simply suggested implementing further studies to address the new hypotheses that are generated by our study. Our pru- dent attitude is demonstrated by the fact that, in contrast to one reviewer's ad- vice, we have not pooled contralateral breast cancer and ipsilateral breast can- cer events in a single figure. While this combination would have certainly pro- vided more powerful statistical support for the benefit of fenretinide in pre- menopausal women, such a combined analysis had not been planned before the study was conducted. The bottom line is that the fenretin ide trial is one of the few large cancer pre- vention trials ever performed and is by far the largest clinical study that tests a retinoid for breast cancer prevention. A warding an F grade to our pioneering study without any sound scientific argu- ment arrogant, cynical, and uselessly mortifying for the nearly 3000 women who took part in the study for an average of 8 years, for the many investigators and support personnel who gave theii time and effort for such a long period of time, for the reviewers who recom- mended National Cancer Institute fund- ing for three consecutive periods for a total of 9 years, and last, but not least, for the U.S. and Italian taxpayers and contributors who made the resources available. We thought it appropriate to submit our paper to the Journal in view of the above-mentioned reasons. We are ex- tremely disappointed by the Journal's decision to publish our paper alongside this destructive editorial without inform- ing us until the moment of its publica- tion. We are sorry the Journal missed an opportunity to begin a fruitful discus- sion on the complex issues related to cancer prevention trials. is UMBERTO VERONESI GIUSEPPE DE PALO ETTORE MARUBINT ALBERTO COSTA LUIGI MARIANI FRANCA FORMELLI ANDREA DECENSI piete? (editorial]. J Nall Cancer Inst 1999;91: (2) Veronesi U, De Palo G, Marubini E, Cosra A, Formelli F, Mariani L, et al. Randomized trial of fenrctinide to prevent second breast malig- nancy in women with early breast cancer. J Natl Cancer Inst 1999;91:1847-56. NOTES Ajfilia11ons of authors: U. Veronesi, A. Costa, A. Deccnsi, European Instirure of Oncology, Mi- lan, Icaly; G. De Palo, E. Marubini, L. Mariani, F. Fonnelli, lstiruto Nazionale Tumori, Milan. Corr~spondenu 10: Umbeno Veronesi, M.D., European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy (e-mail: umberto. vcronesi@ieo.ie). Both the report on the Randomized Trial of Fenretinide to Prevent Second 'Breast Malignancy in Women With Early Breast Cancer and the accompa- ny ing editorial i mpressed me as thoughtful presentations and discussions of the complex results reported (1,2). Why then the sensationalist title for the editorial? If this title was the one chosen by the editorialists, the Journal should have insisted on a more objective title. If the title was selected by the Journal, then shame on the Journal. Certainly the -dismissal by the media of this trial as a poorly done study serves no one well. Doing clinical research is hard enough without our most cited (best ?) journal in cancer research resorting to yellow journalism. FRANK L. MEYSKENS, JR. REFERENCES (1) Veronesi U, De Palo G, Marubini E, Costa A. Formelli F, Mariani L, et al. Randomii.ed trial of fenretinide co prevent second breast malig- nancy in women with early breast cancer. J Natl Cancer Inst 1999;91:1847-56. (2) Piantadosi S. Vitanun A Analogue for bl'C8St cancer prevention: a grade of For incomplete'/ [editorial]. J Natl Cancer Inst I999;9I:l794. NOTE Corrtspondence ro: Frank L. Meyskens Jr .. M.D., Chao Family Comprehensive Cancer Cen- ter, University of California. Irvine. IOI The City Drive South, Rt. 8I, Bldg. 23, Rm. 403, Orange, CA 92868-3298. RESPONSE It's not often that a favorable edito- REFERENCES rial gets taken to task by the recipient. I (I) Pian1ados1 S. Vitamin A analogue for breast cancer prevention: a grade of F or incom- hope that other readers did not miss my points or get them backwards, as Journal of the National Cancer Institute, Vol. 92, No. 3, February 2. 2000