The aim of this study is to evaluate the effectiveness of the synthetic retinoid, fenretinide N-(4hydroxyphenyl) retinamide, HPR, in preventing contralateral primaries in patients already operated on for breast cancer. HPR is a derivative of retinoic acid and it has been shown to inhibit N-nitroso-N-methylurea induced mammary carcinogenesis. It also exhibits an antiproliferative effect on rat mammary epithelium that may be involved in HPR inhibition of mammary carcinogenesis. HPR has also been found to block the combined proliferative effects of insulin and prolactin upon the mammary epithelium growing in vitro. Moreover, HPR is a relatively non toxic retinoid which, unlike many other retinoids, does not accumulate in the liver but in adipose tissure and in the breast. The applicant institution has confirmed this targeted concentration also in humans and has completed a one year randomized Phase I study on 101 breast cancer patients indicating that the recommended dose for fenretinide is 200mg/day with a three day drug holiday every month to prevent the risk of impaired night vision. Due -Lo the unique concentration of HPR, the Milan Cancer institute started in March 1987 a randomized clinical trial to evaluate the capability of this retinoid to reduce the incidence of contralateral breast cancer which is about 1% per year for about ten years after surgery. The applicant institution and its branches in Northern Italy plan to randomize up to 5,000 breast cancer patients with negative axillary lymphnodes, no evidence of disease and who did not receive any adjuvant endocrine or chemotherapy treatment. Patients are randomized for HPR 200mg/d by versus control and followed up every five months with physical examination and annual chest X-rays, bone scan or skeleton X-rays every 18 months and annual mammography of the contralateral breast. The follow-up will be continued for at least seven,years. Since March 1987,314 patients have been randomized in the treated group and 310 in the control group. No contralateral primaries have been recorded.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01CA038567-04
Application #
3548557
Study Section
(SRC)
Project Start
1984-09-30
Project End
1992-04-30
Budget Start
1989-08-10
Budget End
1990-04-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
National Institute for the Study Care Tumors
Department
Type
DUNS #
City
Milan
State
Country
Italy
Zip Code
Formelli, Franca; Camerini, Tiziana; Cavadini, Elena et al. (2003) Fenretinide breast cancer prevention trial: drug and retinol plasma levels in relation to age and disease outcome. Cancer Epidemiol Biomarkers Prev 12:34-41
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Decensi, A; Torrisi, R; Fontana, V et al. (1998) Correlation between plasma transforming growth factor-beta 1 and second primary breast cancer in a chemoprevention trial. Eur J Cancer 34:999-1003
De Palo, G; Camerini, T; Marubini, E et al. (1997) Chemoprevention trial of contralateral breast cancer with fenretinide. Rationale, design, methodology, organization, data management, statistics and accrual. Tumori 83:884-94
Decensi, A; Fontana, V; Fioretto, M et al. (1997) Long-term effects of fenretinide on retinal function. Eur J Cancer 33:80-4
Mariani, L; Formelli, F; De Palo, G et al. (1996) Chemoprevention of breast cancer with fenretinide (4-HPR): study of long-term visual and ophthalmologic tolerability. Tumori 82:444-9

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