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

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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

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Fenretinide
Second Primary Neoplasms
Breast
Breast Neoplasms
Confidence Intervals
Incidence
Arm
Neoplasm Metastasis
Carcinoma, Intraductal, Noninfiltrating
Mortality
Random Allocation
Vitamin A

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Veronesi, U., De Palo, G., Marubini, E., Costa, A., Formelli, F., Mariani, L., ... 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.

Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. / Veronesi, Umberto; De Palo, Giuseppe; Marubini, Ettore; Costa, Alberto; Formelli, Franca; Mariani, Luigi; Decensi, Andrea; Camerini, Tiziana; Del Turco, Marco Rosselli; Di Mauro, Maria Gaetana; Muraca, Maria Grazia; Del Vecchio, Marcella; Pinto, Carmine; D'Aiuto, Giuseppe; Boni, Corrado; Campa, Tiziana; Magni, Andrea; Miceli, Rosalba; Perloff, Marjorie; Malone, Winfred F.; Sporn, Michael B.

In: Journal of the National Cancer Institute, Vol. 91, No. 21, 03.11.1999, p. 1847-1856.

Research output: Contribution to journalArticle

Veronesi, U, De Palo, G, Marubini, E, Costa, A, Formelli, F, Mariani, L, Decensi, A, Camerini, T, Del Turco, MR, Di Mauro, MG, Muraca, MG, Del Vecchio, M, Pinto, C, D'Aiuto, G, Boni, C, Campa, T, Magni, A, Miceli, R, Perloff, M, Malone, WF & Sporn, MB 1999, 'Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer', Journal of the National Cancer Institute, vol. 91, no. 21, pp. 1847-1856.
Veronesi, Umberto ; De Palo, Giuseppe ; Marubini, Ettore ; Costa, Alberto ; Formelli, Franca ; Mariani, Luigi ; Decensi, Andrea ; Camerini, Tiziana ; Del Turco, Marco Rosselli ; Di Mauro, Maria Gaetana ; Muraca, Maria Grazia ; Del Vecchio, Marcella ; Pinto, Carmine ; D'Aiuto, Giuseppe ; Boni, Corrado ; Campa, Tiziana ; Magni, Andrea ; Miceli, Rosalba ; Perloff, Marjorie ; Malone, Winfred F. ; Sporn, Michael B. / Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. In: Journal of the National Cancer Institute. 1999 ; Vol. 91, No. 21. pp. 1847-1856.
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title = "Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer",
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.",
author = "Umberto Veronesi and {De Palo}, Giuseppe and Ettore Marubini and Alberto Costa and Franca Formelli and Luigi Mariani and Andrea Decensi and Tiziana Camerini and {Del Turco}, {Marco Rosselli} and {Di Mauro}, {Maria Gaetana} and Muraca, {Maria Grazia} and {Del Vecchio}, Marcella and Carmine Pinto and Giuseppe D'Aiuto and Corrado Boni and Tiziana Campa and Andrea Magni and Rosalba Miceli and Marjorie Perloff and Malone, {Winfred F.} and Sporn, {Michael B.}",
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T1 - Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer

AU - Veronesi, Umberto

AU - De Palo, Giuseppe

AU - Marubini, Ettore

AU - Costa, Alberto

AU - Formelli, Franca

AU - Mariani, Luigi

AU - Decensi, Andrea

AU - Camerini, Tiziana

AU - Del Turco, Marco Rosselli

AU - Di Mauro, Maria Gaetana

AU - Muraca, Maria Grazia

AU - Del Vecchio, Marcella

AU - Pinto, Carmine

AU - D'Aiuto, Giuseppe

AU - Boni, Corrado

AU - Campa, Tiziana

AU - Magni, Andrea

AU - Miceli, Rosalba

AU - Perloff, Marjorie

AU - Malone, Winfred F.

AU - Sporn, Michael B.

PY - 1999/11/3

Y1 - 1999/11/3

N2 - 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.

AB - 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.

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