Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer

Umberto Veronesi, Giuseppe De Palo, Ettore Marubini, Alberto Costa, Franca Formelli, Luigi Mariani, Andrea Decensi, Tiziana Camerini, Marco Rosselli Del Turco, Maria Gaetana Di Mauro, Maria Grazia Muraca, Marcella Del Vecchio, Carmine Pinto, Giuseppe D'Aiuto, Corrado Boni, Tiziana Campa, Andrea Magni, Rosalba Miceli, Marjorie Perloff, Winfred F. MaloneMichael B. Sporn

Research output: Contribution to journalArticle

Abstract

Background: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. Methods: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. Results: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P = .642) or ipsilateral breast cancer (P = .177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes = .045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0.92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82- 2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1.89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. Conclusions: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.

Original languageEnglish
Pages (from-to)1847-1856
Number of pages10
JournalJournal of the National Cancer Institute
Volume91
Issue number21
Publication statusPublished - Nov 3 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Veronesi, U., De Palo, G., Marubini, E., Costa, A., Formelli, F., Mariani, L., Decensi, A., Camerini, T., Del Turco, M. R., Di Mauro, M. G., Muraca, M. G., Del Vecchio, M., Pinto, C., D'Aiuto, G., Boni, C., Campa, T., Magni, A., Miceli, R., Perloff, M., ... Sporn, M. B. (1999). Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. Journal of the National Cancer Institute, 91(21), 1847-1856.