Synthetic Retinoid May Protect Against Breast Cancer Recurrence in Younger Women

WASHINGTON--Interim results from an on-going Italian chemopreven-tiontrial of a synthetic retinoid show a "borderline significant"protective effect against contralateral breast cancer and, toa lesser degree, against ovarian cancer, but only in premenopausalwomen.

The researchers from the European Institute of Oncology in Milanand Italy's National Cancer Institutes observed a small increasedrisk of recurrence in postmenopausal breast cancer patients, AndreaU. Decensi, MD, reported at the American Association for CancerResearch meeting. "Menopause modifies the intervention effect,"he said.

Dr. Decensi, a cancer chemopreven-tion researcher at the cancercenters in Milan and Genoa, noted the similarity of these findingsto those with tamoxifen (Nolvadex), which has antagonistic effectson estrogen target organs, ie, it decreases the risk of recurrentbreast cancer but increases endometrial cancer risk.

"When we deal with biological response modifiers, we cannotexpect a single dose-response effect, as is seen with conventionalchemotherapy," he said.

Between 1987 and 1993, the Italian phase III trial recruited 2,972women with previous stage I breast cancer who were at low riskof recurrence. The women were randomized to receive 200 mg/dayof the synthetic retinoid fenretinide, or 4-HPR, for 5 years,or to get no treatment, with follow-up for 7 years. The interimanalysis reported by Dr. Decensi was performed at a median of70 months.

Although preliminary, the results seem to suggest that menopausalstatus and/or age significantly modulates the inter-ventionalresponse to fenretinide, with premenopausal women gaining a protectiveeffect. This suggests that retinoids somehow interfere with estrogen'smechanism of action, Dr. Decensi said.

Based on previous pilot studies showing that fenretinide significantlymodulates plasma IGF-I concentrations in young women, the roleof plasma IGF-I levels is also being evaluated as a surrogateendpoint biomarker in premenopausal women, he said.

Dr. Decensi also said that the Italian team has enrolled 4,304healthy women with a family history of breast cancer in a 5-year,randomized test of tamoxifen's chemopreventive effects againstbreast cancer. The study is limited to women who have had hysterectomies.