Genistein, a component of soy, was administered to prepubertal female Sprague-Dawley CD rats and investigated for chemoprevention against mammary cancer. Genistein, at 500 microgram/g body wt or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO), was injected (s.c.) on days 16, 18 and 20 post-partum. At day 50 post-partum all animals were exposed to 80 microgram dimethylbenz[a]anthracene (DMBA) per g body wt. Animals treated prepubertally with genistein as compared to DMSO had reduced incidence and significantly fewer adenocarcinomas per animal. Mammary whole mount analysis showed that prepubertal genistein treatment resulted in mammary glands of 50-day-old rats developing fewer terminal end buds and more lobules II. Cell proliferation studies with bromodeoxyuridine (BrdU) showed that terminal end buds from mammary glands of 50-day-old females treated prepubertally with genistein had significantly fewer cells in S-phase of the cell cycle. Serum genistein concentrations in 21- and 50-day-old females following prepubertal genistein treatment were 4.2 +/- 0.6 micromol and 102 +/- 30 nM, respectively. Animals treated prepubertally with genistein as compared to vehicle spent more time in the estrus phase of the estrus cycle, although all animals did cycle. In 50-day-old females, circulating estradiol-17 beta and progesterone concentrations were not significantly altered by the prepubertal genistein treatment. Oocyte/follicle counts and numbers of atretic follicles and corpora lutea were not significantly different between the genistein- and vehicle-treated animals. We conclude that genistein treatment during the prepubertal period can suppress the development of chemically-induced mammary cancer without significant toxicity to the endocrine/reproductive system.

Breast cancer is the most common cancer in US females and is the second leading cause of cancer death among women. By contrast, Asian women consuming a traditional diet high in soy products have a relatively low incidence of breast cancer. Asians who emigrate to the United States and adopt a Western diet lose this protection. Soy-based diets are high in phytoestrogens, and one of these components is genistein. Using the dimethylbenz(a)anthracene (DMBA) mammary cancer rodent model, we have investigated the breast cancer protective potential of genistein. Our results demonstrate that neonatal and prepubertal genistein treatments altered the ontogeny of the mammary gland and rendered the adult animals less susceptible to chemically-induced mammary cancer. Neonatal genistein treatment did not significantly alter the rate of formation and persistence of DMBA-DNA adducts in the mammary gland. While high concentrations of genistein during the neonatal period caused adverse effects on ovarian follicular development, prepubertal genistein treatment did not appear to be toxic in either the female reproductive tract or the endocrine system.

Accurate assessment of utilities to calculate quality-adjusted life expectancy for medical interventions is needed in cirrhosis. To date, limited data exist in cirrhotics and are generally physician-assigned. Therefore, our aim was to determine utilities for six clinical scenarios in cirrhosis and to define if differences exist in utilities assigned by physicians versus patients. We administered a questionnaire to 83 physicians and 114 cirrhotics to obtain utilities using the time trade-off method for (1) compensated cirrhosis, (2) decompensated cirrhosis, (3) encephalopathy, (4) spontaneous bacterial peritonitis, (5) variceal bleeding, and (5) hepatocellular carcinoma. On a scale from 0 (death) to 1 (perfect health), mean utilities of physicians and patients were compared using the Student t test. One-way analysis of variance was used to compare the utilities between patients according to Child-Pugh class. Statistical significance was defined as a P value <0.05. The mean age of the physicians was 42 +/- 11, with 52% being male. The mean age of the patients was 52 +/- 9; with 59% male. The mean Child-Pugh score was 8 +/- 2 and HCV was the most common etiology (54%). The mean utilities for physicians and patients were as follows: CC, 0.78 vs. 0.88; DC, 0.55 vs. 0.74; E, 0.38 vs. 0.55; SBP, 0.33 vs. 0.45; VB, 0.27 vs. 0.40; and HCC, 0.19 vs. 0.30. All comparisons were statistically significant. Although physicians and patients assigned similar relative rankings to each health state, physicians assigned utilities were significantly different from those assigned by patients. These results suggest that studies that have used physician-assigned utilities do not accurately reflect patient preferences.