Fenretinide as Breast Cancer Chemoprevention?
by Drea Thew
A risk-reducing option that is safe, effective and widely-accepted for women at high hereditary risk for breast cancer remains elusive. Recent results from a long-term study may be a step in the right direction.
Italian researchers report that fenretinide, a synthetic relative of Vitamin A, can prevent secondary breast cancers in premenopausal women. The researchers concluded that fenretinide should be investigated further for prevention of breast cancer in young women at high risk.” The drug is currently unavailable in the United States.
The study included 1,739 women who were previously diagnosed with Stage 1 breast cancer or DCIS, and who were not treated with chemotherapy. Participants were randomly chosen to receive either no treatment or 200mg of fenretinide daily (with a monthly three-day break) for five years. Over 15 years—the study period included 10 years beyond the end of participants’ fenretinide treatment—both groups of women were observed for any occurrence of breast cancer, including new primary cancers and recurrences of their original cancers.
Overall, the difference in second breast cancers between the two groups was small. Those who took fenretinide had a 17 percent lower incidence than the no-treatment group. However, when participant groups were compared based on menopausal status, fenretinide was more effective in premenopausal women. In fact, the younger the woman, the more fenretinide appeared to reduce her risk. The study authors estimate a 35 percent risk reduction in women under 50 and a 50-percent risk reduction in women under age 40. The protective effect of the medication seemed to disappear around age 55, actually somewhat increasing the risk of second breast cancer in these women.
Other studies have shown that fenretinide may work against ER-positive and ER-negative breast cancer cells. This may be good news for women with BRCA1 mutations who typically develop cancers that are estrogen-receptor negative, and for whom hormonal therapy may not be an option. In a previous study, researchers found that fenretinide reduced second breast cancers in premenopausal women regardless of the hormone receptor status of their initial cancer.
The Italian study also observed the incidence of ovarian cancer in participants. While the rate of ovarian cancer over the course of the 15 years was similar between the two groups, women receiving fenretinide did not develop ovarian cancer during the five years they were on the medication.
Side effects of fenretinide may include diminished ability to adjust eyesight in darkness (“night blindness”) and mild skin disorders. These effects occurred in about 20 percent of study participants; 4.4 percent of women found the effects bothersome enough to discontinue treatment. There is also concern that fenretinide, like other retinoids (Vitamin A and other substances that function like vitamin A in the body), may cause birth defects, so reliable birth-control during treatment would be crucial.
The women in this study were not BRCA tested, so we don’t know if fenretinide will work equally well in young BRCA carriers with breast cancer. In addition, the participants already had a cancer diagnosis in one breast. The study did not look at fenretinide as a chemopreventive agent to prevent breast cancer in high-risk women who never had breast cancer. Dr. Michael Sporn, Professor of Pharmacology and Medicine at Dartmouth Medical School, cancer chemoprevention expert, and one of the study authors, notes that “[fenretinide] could be used in combination with SERMs such as tamoxifen or raloxifene as a preventive agent, since other retinoids have been shown to synergize nicely with both…in studies in experimental animals.” Asked whether the drug may be studied as a chemoprevention agent in BRCA carriers, Dr. Sporn is skeptical. Although fenretinide could be effective chemoprevention for our population, there is little financial incentive for any company to invest in its research and development because the patent on fenretinide has expired. However, through FORCE, our community has the power to advocate for more funding for research on hereditary cancer and better options for ourselves and future generations.
Drea Thew is a FORCE Helpline volunteer.
U Veronesi, L Mariani, A Decensi, F Formelli, T Camerini, et al. Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Annals of Oncology, 2006; 17: 1065- 1071.
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