Veronesi U et al. (2006) Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Ann Oncol 17: 1065–1071

A 15-year follow-up study by Veronesi et al. has demonstrated that the synthetic retinoid fenretinide can reduce the risk of second breast cancer by 50% in premenopausal women aged 40 years or younger with early-stage breast cancer.

The researchers analyzed data from a subgroup of 1,739 women enrolled in a phase III trial of fenretinide efficacy and who continued long-term follow-up at the Istituto Nazionale Tumori in Milan, Italy. Women with a diagnosis of stage I primary breast cancer who had received first-line therapy were randomized to undergo either observation or treatment with fenretinide 200 mg daily for 5 years. Incidence of both contralateral and ipsilateral second breast cancers was recorded. After a median follow-up of 14.6 years, the rate of second breast cancers in the fenretinide group was 17% lower than in the observation group. When the data were stratified by menopausal status, however, premenopausal women receiving fenretinide had a significantly lower risk of developing second breast cancer than postmenopausal women (hazard ratio 0.62; 95% CI 0.46–0.83). Hazard curves indicated that fenretinide reduces risk by 51% and 48% in women aged 35 years or younger and 40 years or younger, respectively. This protective effect lasted for up to 15 years; that is, up to 10 years after completion of fenretinide therapy.

The authors conclude that these data provide the rationale for a trial of fenretinide chemoprevention in healthy premenopausal women at high risk of breast cancer, such as those with BRCA1 or BRCA2 mutations.