The specific aim of the present application is to validate plasma insulin-like growth factor-I (IGF-1) as a surrogate endpoint of contralateral breast cancer in women, aged less that 50 years, on intervention with the synthetic retinoid 4-(hydroxyphenyl) retinamide (fenretinide or 4-HPR). This will be accomplished by assessing the relationship between the incidence of contralateral breast cancer and the change in plasma concentrations of total or unbound IGF-I (the latter expressed as IGF-I/IGF binding protein-3 ratio). The analysis will be integrated into the ongoing phase III trial of a five-year intervention with 4-HPR at the daily dose of 200 mg. Previous pilot studies of 4-HPR have demonstrated a significant reduction of total and unbound IGF-I in women aged less than 50 years. In addition, an interim analysis of the ongoing, phase III trial involving 2,972 stage I breast cancer women aged 30-70 years indicates that 4-HPR reduces ovarian and contralateral breast cancers in young or premenopausal women. The sample on study will include a subgroup of 641 women aged less than 50 years (377 on 4-HPR intervention and 264 untreated controls) in whom plasma aliquot are available both at baseline and during the intervention period. The analysis will be performed after three years when the highest number of contralateral tumors will be available. Although contralateral breast cancer involves a selected target population, validation of the biomarker as an intermediate endpoint in this setting may provide insight into breast carcinogenesis. This may help to select more specific agents and to implement more efficient intervention trials with 4-HPR in the future, particularly a wider group of high risk subjects, including young women with genetic susceptibility to breast and ovarian cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA072286-01
Application #
2010418
Study Section
Special Emphasis Panel (SRC (P1))
Project Start
1997-08-01
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Istituto Europeo Di Oncologia
Department
Type
DUNS #
City
Milan
State
Country
Italy
Zip Code
20141
Zanardi, S; Serrano, D; Argusti, A et al. (2006) Clinical trials with retinoids for breast cancer chemoprevention. Endocr Relat Cancer 13:51-68
Veronesi, U; Mariani, L; Decensi, A et al. (2006) Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Ann Oncol 17:1065-71
Serrano, Davide; Bonanni, Bernardo; Cazzaniga, Massimiliano et al. (2003) Pharmacological prevention of breast cancer: quo vadis? Breast 12:379-86
Decensi, Andrea; Veronesi, Umberto; Miceli, Rosalba et al. (2003) Relationships between plasma insulin-like growth factor-I and insulin-like growth factor binding protein-3 and second breast cancer risk in a prevention trial of fenretinide. Clin Cancer Res 9:4722-9
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
Decensi, Andrea; Serrano, Davide; Bonanni, Bernardo et al. (2003) Breast cancer prevention trials using retinoids. J Mammary Gland Biol Neoplasia 8:19-30
Veronesi, U; Decensi, A (2001) Retinoids for ovarian cancer prevention: laboratory data set the stage for thoughtful clinical trials. J Natl Cancer Inst 93:486-8
Decensi, A; Johansson, H; Miceli, R et al. (2001) Long-term effects of fenretinide, a retinoic acid derivative, on the insulin-like growth factor system in women with early breast cancer. Cancer Epidemiol Biomarkers Prev 10:1047-53
Formelli, F (2000) Quality control for HPLC assay and surrogate end point biomarkers from the fenretinide (4-HPR) breast cancer prevention trial. J Cell Biochem Suppl 34:73-9
Decensi, A; Bonanni, B; Guerrieri-Gonzaga, A et al. (2000) Chemoprevention of breast cancer: the Italian experience. J Cell Biochem Suppl 34:84-96

Showing the most recent 10 out of 11 publications