WASHINGTON--Interim results from an on-going Italian chemopreven-tion trial of a synthetic retinoid show a "borderline significant" protective effect against contralateral breast cancer and, to a lesser degree, against ovarian cancer, but only in premenopausal women.
The researchers from the European Institute of Oncology in Milan and Italy's National Cancer Institutes observed a small increased risk of recurrence in postmenopausal breast cancer patients, Andrea U. Decensi, MD, reported at the American Association for Cancer Research meeting. "Menopause modifies the intervention effect," he said.
Dr. Decensi, a cancer chemopreven-tion researcher at the cancer centers in Milan and Genoa, noted the similarity of these findings to those with tamoxifen(Drug information on tamoxifen) (Nolvadex), which has antagonistic effects on estrogen target organs, ie, it decreases the risk of recurrent breast cancer but increases endometrial cancer risk.
"When we deal with biological response modifiers, we cannot expect a single dose-response effect, as is seen with conventional chemotherapy," he said.
Between 1987 and 1993, the Italian phase III trial recruited 2,972 women with previous stage I breast cancer who were at low risk of recurrence. The women were randomized to receive 200 mg/day of the synthetic retinoid fenretinide, or 4-HPR, for 5 years, or to get no treatment, with follow-up for 7 years. The interim analysis reported by Dr. Decensi was performed at a median of 70 months.
Although preliminary, the results seem to suggest that menopausal status and/or age significantly modulates the inter-ventional response to fenretinide, with premenopausal women gaining a protective effect. This suggests that retinoids somehow interfere with estrogen's mechanism of action, Dr. Decensi said.
Based on previous pilot studies showing that fenretinide significantly modulates plasma IGF-I concentrations in young women, the role of plasma IGF-I levels is also being evaluated as a surrogate endpoint biomarker in premenopausal women, he said.