fenretinide and Hot-Flashes

Digital nuclear morphometric analysis can capture subtle differences along neoplastic progression. Studies showed different profiles from normal to cancer lesions. Our goal is to utilize this method as biomarker in chemoprevention trials.. Postmenopausal women were randomized to oral (CEE) or transdermal (E2) estrogen replacement therapy (ERT) in association with fenretinide or placebo. Ultrasound-guided fine needle aspiration (FNA) was performed at baseline and after 12 months in a subset of subjects.. Ten samples were analyzed by karyometry. E2 compared with CEE increased nuclear area (p=0.01). A similar pattern was observed for other DNA content and chromatin texture features. Fenretinide vs. placebo, increased nuclear area and shape while decreased slope, peak and entropy.. Preliminary results indicate that nuclear morphometry is feasible on FNA samples. ERT and fenretinide induced significant karyometric changes. These results support further investigation of this procedure as surrogate biomarker in chemoprevention trial.

Topics: Administration, Cutaneous; Administration, Oral; Biopsy, Fine-Needle; Breast; Chemoprevention; Disease Progression; Drug Therapy, Combination; Estradiol; Estrogen Replacement Therapy; Female; Fenretinide; Hot Flashes; Humans; Image Processing, Computer-Assisted; Karyometry; Middle Aged; Postmenopause; Predictive Value of Tests

Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) relief menopause symptoms, but may increase breast cancer risk, while the effects of transdermal estradiol (E2) and MPA are less known. In previous studies, fenretinide decreased second breast malignancies in premenopausal but not in postmenopausal women, suggesting a hormone-sensitizing effect. We have evaluated the quality of life through a self-administered questionnaire during a randomized study of oral CEE or transdermal E2 and fenretinide or placebo.. A total of 226 postmenopausal women were randomly assigned to either CEE 0.625mg/day and placebo (n=55), or CEE and fenretinide 100mg/bid (n=56), or E2, 50microg/day and placebo (n=59), or E2 and fenretinide (n=56) for 12 months. Sequential MPA 10mg/day was added in all groups. Treatment effects were investigated using a validated questionnaire, the Menopause Quality of Life questionnaire (MENQOL).. Oral CEE and transdermal E2 have a comparable activity in reducing menopausal symptoms (p=ns). Both routes ameliorate significantly the symptoms after 1 year of treatment (p<0.0001). Fenretinide does not modify the effects of hormonal replacement therapy.. Oral CEE and transdermal E2 have similar effect on menopausal symptoms relief. The choice of the best estrogen replacement therapy (ERT) route should be decided based on a careful analysis of all the clinical aspects of every subject, considering that transdermal therapy may have a safer effect on the cardiovascular system.

Topics: Administration, Cutaneous; Administration, Oral; Drug Administration Schedule; Drug Therapy, Combination; Estradiol; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Fenretinide; Hot Flashes; Humans; Medroxyprogesterone Acetate; Menopause; Middle Aged; Quality of Life; Surveys and Questionnaires; Treatment Outcome