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 language | English |
|---|---|
| Pages (from-to) | 1847-1856 |
| Number of pages | 10 |
| Journal | Journal of the National Cancer Institute |
| Volume | 91 |
| Issue number | 21 |
| Publication status | Published - Nov 3 1999 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=0033520713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033520713&partnerID=8YFLogxK
M3 - Article
C2 - 10547391
AN - SCOPUS:0033520713
VL - 91
SP - 1847
EP - 1856
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 21
ER -