Fenretinide cuts risk of second breast cancer in younger women

[unseennude]

Treatment for 5 years with the vitamin A analog fenretinide significantly reduces the risk of second breast cancers in premenopausal women, especially at younger ages, and the protection persists for several years after treatment. In postmenopausal women, however, fenretinide increases the risk of second breast tumors.

These findings are from a 15-year follow-up study of 1739 women who received 200 mg fenretinide daily or no extra treatment after surgery for early breast cancer as part of a phase III randomized trial of fenretinide to prevent contralateral or second ipsilateral breast cancer.

After 8 years, there were no significant between-group differences overall in the incidence of contralateral or ipsilateral breast cancer. However, a post-hoc analysis at the time suggested a significant treatment interaction with menopausal status (or age), with a 35% reduction in premenopausal women (or women < 50 years) and an opposite trend in postmenopausal women (or women > 50 years).

Fifteen-year follow up data, reported in the May 4th online issue of Annals of Oncology, confirm and extend the results seen at 8 years, Dr. Umberto Veronesi, from the European Institute of Oncology in Milan and colleagues report.

Fenretinide induced a 17% durable reduction of second breast cancer incidence overall, which approached statistical significance, according to the report.

"When the analysis was stratified by menopausal status, there was a 38% statistically significant reduction of second breast cancers in premenopausal women," Dr. Veronesi and colleagues report. "Most notably," they write, fenretinide was associated with a 50% risk reduction in second breast cancers in women aged 40 years or younger.

The protective effect persisted for up to 15 years after fenretinide was discontinued. "Interestingly, the different effect of fenretinide according to age recalls the effect of first full term pregnancy on breast cancer risk, which is protective at a young age and deleterious at an older age," Dr. Veronesi's team points out.

Because fenretinide-related side effects are "limited," this retinoid "should be investigated further for prevention of breast cancer in young women at high-risk," the investigators conclude