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Synthetic Retinoid May Protect Against Breast Cancer Recurrence in Younger Women

Synthetic Retinoid May Protect Against Breast Cancer Recurrence in Younger Women

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

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 (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.


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