Chemoprevention of cancer represents a challenge for oncology during this n
ew millennium. Substantial advances have been accomplished in the last deca
de, especially for primary and secondary prevention of breast cancer. In ad
dition to tamoxifen, raloxifene and other selective estrogen receptor modul
ators, retinoids are among the most promising agents, given their ability t
o inhibit mammary carcinogenesis in preclinical models.
Fenretinide, the synthetic amide of retinoic acid, inhibits cell growth mos
tly through the induction of apoptosis with mechanisms which may partly inv
olve the retinoid receptors. Because it has a favourable toxicological prof
ile, fenretinide has been extensively investigated in clinical trials. A la
rge randomised phase III trial for secondary breast cancer prevention has b
een recently carried out in Italy. Results showed a reduction of second bre
ast malignancies in premenopausal women. In addition, a significant decreas
e of circulating insulin-like growth factor (IGF)-1, a known risk factor fo
r premenopausal breast cancer, was observed after 1 year of fenretinide adm
inistration in premenopausal women with breast cancer.
Ongoing studies on the validation of the circulating IGF-1 as a surrogate e
ndpoint biomarker of fenretinide activity and on the effectiveness of the c
ombination with low dose tamoxifen may provide further insight into the fut
ure clinical application of fenretinide.