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A Decensi

Publications and source records attributed to A Decensi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Recent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer.

Chemoprevention is a recently introduced and rapidly growing area of oncology that is identifying agents with a potentially preventive role in cancer. Several clinical trials have recently shown the feasibility of this approach in reducing the risk of major human cancers. In the USA, a large trial that demonstrated a reduction of approximately 50% in the risk of developing breast cancer led to Food and Drug Administration (FDA) approval of tamoxifen as a preventive agent in women at increased risk. Although the results could not be reproduced in two smaller European trials, further investigations into this agent are clearly warranted. Raloxifene, another selective oestrogen receptor modulator which has reduced the risk of breast cancer in a trial in women with osteoporosis, is being compared with tamoxifen in a large primary prevention trial in at-risk women. Retinoids are a group of compounds that have proved especially effective in reducing the occurrence of second primary tumours in subjects with skin, head and neck or liver cancer. Fenretinide, a synthetic retinoic acid derivative, has recently been shown to decrease the occurrence of a second breast malignancy in premenopausal women. Results with non-steroidal anti-inflammatory drugs (NSAIDs) have proved consistently encouraging in epidemiological studies in lowering the incidence of colorectal cancer. Clinical trials with selective cyclo-oxygenase inhibitors potentially devoid of gastrointestinal (GI) toxicity are currently underway in at-risk subjects. Calcium and selenium have also received much attention as chemopreventive agents. Originally investigated against skin cancer, selenium showed efficacy in reducing prostate, lung and colon cancer incidence. Similarly, vitamin E was effective in reducing prostate cancer incidence and mortality in a lung cancer prevention trial in heavy smokers. The challenges of conducting well-designed and unequivocal chemoprevention trials are considerable, but advances in techniques of identification of at-risk subjects and establishing surrogate endpoint biomarkers should contribute greatly to future studies. Current knowledge suggests that a pharmacological approach to preventing cancer, using natural or synthetic agents, could become an important way forward.

Antineoplastic Agents↗
PubMed2000

Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point.

Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers. A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07). There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36). Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer.

Aged↗
PubMed2000

Ocular effects of fenretinide, a vitamin A analog, in a chemoprevention trial of bladder cancer.

Fenretinide is a vitamin A derivative under investigation in cancer prevention trials. Because all available pharmacologic and toxicologic data were obtained from breast cancer patients, we measured plasma drug, metabolite, and vitamin A levels and studied their relationship with visual and ocular symptoms in a cohort formed mostly by male subjects belonging to a bladder cancer prevention trial. After 1 year, the mean plasma retinol levels (+/- standard deviation [SD]) were 168.2 +/- 75.8 ng/ml in 31 subjects treated with fenretinide and 594.5 +/- 168.4 ng/ml in 36 control subjects (P < .001). Plasma retinol levels were correlated inversely to drug and metabolite concentrations, which in turn were correlated inversely to the interval from last drug intake. The decline of plasma vitamin A levels accounted for a 41.7% cumulative incidence of diminished dark adaptability in the retinoid arm as compared to 6.8% in the control arm (odds ratio = 13.8; 95% confidence interval, 2.9-66.1). Although compliance as assessed by capsule count was high, three subjects originally assigned to the treatment group who proved to be noncompliers (8.8%, or 3 of 34) had no detectable plasma drug or metabolite levels. Our data confirm the specific pharmacologic and visual effects of fenretinide also in a male population and strengthen the importance of multiple blood measurements to monitor treatment compliance in prevention trials.

Adult↗
PubMed1999

Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.

BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.

Adult↗
PubMed1999

Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial.

Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra-individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper-Diploid-Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle-invasive bladder cancer, indicating the "low-risk" features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis.

Antineoplastic Agents↗
PubMed1999

Effect of tamoxifen on lipoprotein(a) and insulin-like growth factor-I (IGF-I) in healthy women.

Studies in breast cancer patients have shown that tamoxifen decreases circulating levels of lipoprotein(a) (Lp(a)), an independent risk factor for premature coronary heart disease, and insulin-like growth factor-I (IGF-I), a promising surrogate biomarker for breast cancer. Since a common hormone regulatory pathway has been suggested for both biomarkers, we measured Lp(a) levels for 6 months in 68 healthy women participating in a chemoprevention trial of tamoxifen and correlated its changes with IGF-I. After 1 month, mean Lp(a) levels decreased by 23% with tamoxifen and increased by 6% with placebo (P = 0.033). No further change was observed after 2 and 6 months. Women with abnormal values at baseline (i.e. > 30 mg/dl) showed the highest reduction. The mean levels of IGF-I decreased by 23.5% with tamoxifen and remained stable with placebo, but the changes induced by tamoxifen in Lp(a) and IGF-I levels were uncorrelated. Our results support the observation that tamoxifen may be a suitable preventive option for women with multiple disease risk factors.

Adult↗
PubMed1999

Effect of fenretinide on bone mineral density and metabolism in women with early breast cancer.

Prolonged administration of natural or synthetic retinoids has been associated with significant skeletal abnormalities, including osteoporosis. We studied the effects of the synthetic retinoid fenretinide (N-4-hydroxyphenylretinamide, or 4-HPR) administered for a mean of 40 months on bone mineral density and metabolism in 66 consecutive women with early breast cancer belonging to a secondary prevention trial. The mean (+/-SD) bone mineral density at the distal and ultradistal forearm were, respectively, 0.61+/-0.08 and 0.30+/-0.05 g/cm2 in 33 treated women and 0.62+/-0.07 and 0.29+/-0.07 g/cm2 in 33 control women (p = ns for both). Also, no significant difference was observed in markers of bone formation such as bone alkaline phosphatase and osteocalcin, nor in urinary bone resorption markers such as calcium, hydroxyproline, and type I bone collagen cross-linked N-telopeptide (NTx). However, a border-line higher excretion of urinary calcium and NTx was found in the 4-HPR group after adjustment for menopausal status. We conclude that prolonged administration of 4-HPR is not associated with significant alterations of bone mineral density of the forearm. However, a trend towards an increase in bone resorption markers suggests the need for further assessment at different skeletal sites.

Aged↗
PubMed1999

Effect of blood tamoxifen concentrations on surrogate biomarkers in a trial of dose reduction in healthy women.

PURPOSE: Tamoxifen administered at 20 mg/d has been shown to decrease breast cancer incidence in at-risk women by 50%, but toxicity may limit its broad use, particularly in postmenopausal women. Because toxicity may be dose-dependent, we studied the biologic activity of low concentrations of tamoxifen to determine the plausibility of a dose reduction. PATIENTS AND METHODS: We measured the blood concentrations of tamoxifen and its main metabolites in a dose titration study in 105 healthy women (placebo, tamoxifen 10 mg on alternate days, tamoxifen 10 mg/d, and tamoxifen 20 mg/d). Drug levels measured after 2 months of treatment were correlated with the changes in surrogate biomarkers of different diseases, including lipid profile, blood cell count, fibrinogen, antithrombin III, osteocalcin, and insulin-like growth factor I, a promising surrogate biomarker of breast cancer. RESULTS: The means (+/- SD) for tamoxifen and N-desmethyltamoxifen (metabolite X) concentrations (ng/mL) were dose-related, being, respectively, 0 and 0 with placebo, 26.8 +/- 15.1 and 43.7 +/- 22.5 with 10 mg every other day, 51.2 +/- 24.1 and 90.7 +/- 48.0 with 10 mg/d, and 136.0 +/- 52.7 and 230.6 +/- 75.0 with 20 mg/d of tamoxifen. At variance, the biomarker changes were of comparable magnitude at any drug concentration except for platelet count and triglycerides levels, the latter showing a trend to an increase with increasing tamoxifen concentrations. CONCLUSION: An 80% reduction in blood concentrations does not seem to affect the activity of tamoxifen on biomarkers of cardiovascular or breast cancer risk and may in fact have a more favorable safety profile. Additional studies are warranted to determine the most appropriate dose of this agent.

Antineoplastic Agents, Hormonal↗
PubMed1998

Biologic activity of tamoxifen at low doses in healthy women.

BACKGROUND: Results of a clinical trial recently completed in the United States indicate that administration of tamoxifen (20 mg/day) to women at risk can reduce breast cancer incidence by approximately 50% but is associated with an increased risk of developing endometrial cancer and venous thromboembolic events. Since these adverse effects may be dose related, we investigated the effect of tamoxifen on several biomarkers when the drug was given at doses lower than those currently in use. METHODS: In two sequential experiments, 127 healthy hysterectomized women aged 35-70 years were randomly assigned to one of the following four treatment arms: placebo (n = 31) or tamoxifen at 20 mg/day (n = 30) (first experiment); or tamoxifen at 10 mg/day (n = 34) or tamoxifen at 10 mg/ alternate days (n = 32) (second experiment). Baseline and 2-month measurements of the following parameters were compared: 1) total cholesterol (primary end point) and other surrogate markers of cardiovascular disease, e.g., low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and lipoprotein(a); 2) blood cell count; 3) fibrinogen; 4) antithrombin III; 5) osteocalcin; and, 6) in a subgroup of 103 women, insulin-like growth factor-I (IGF-I), a possible surrogate marker for breast cancer. RESULTS: After adjustment for the baseline values, there were reductions in circulating levels of total cholesterol and IGF-I of the same magnitude in all three tamoxifen treatment arms. A similar pattern was observed for most of the other parameters. In the placebo arm, fibrinogen level, which showed a decrease, was the only parameter exhibiting change. CONCLUSIONS: Up to a 75% reduction in the conventional dose of tamoxifen (i.e., 20 mg/day) does not affect the activity of the drug on a large number of biomarkers, most of which are surrogate markers of cardiovascular disease. This study was hypothesis generating, and larger studies are warranted to assess the efficacy of tamoxifen at low doses.

Adult↗
PubMed1998

Effect of fenretinide on plasma IGF-I and IGFBP-3 in early breast cancer patients.

Growing evidence substantiates the role of the insulin-like growth factor I (IGF-1) system in breast tumorigenesis. Retinoids have been shown to affect the IGF system several experimental models. We extended our previous data on plasma IGF-1 modulation by the synthetic retinoid fenretinide (4-HPR) and investigated the effect of the retinoid on plasma IGF binding protein (BP)-3, the major protein binding IGFs. IGF-1 and IGFBP-3 were measured on plasma samples obtained at randomization and after an interval of approximately 1 year, from 39 and 33 stage 1 breast cancer patients assigned to receive 4-HPR, and from 39 and 34 untreated controls, respectively. There was a significant decrease in plasma IGF-1 after 4-HPR administration, whereas no significant change was observed in controls. The effect of 4-HPR on IGF-1 levels was modified by menopausal status, inasmuch as the decrease in IGF-1 was particularly pronounced in pre-menopausal women, whereas the reverse was observed in untreated controls. By contrast, treatment induced an increase of IGFBP-3 with respect to controls. As a result of this dual effect, the bioavailability of IGF-1 for interaction with receptors at target levels further decreased in pre-menopausal 4-HPR treated patients compared with controls, suggesting that retinoid administration may result in lower concentrations of biologically active IGF-1. Our findings may have important implications for the clinical preventive activity of this retinoid.

Adult↗
PubMed1998

Prevention of breast cancer: focus on chemoprevention.

Present prospects of breast cancer prevention are being developed in three main areas: (a) genetics, to understand the real importance of familial breast cancer and genetic testing; (b) lifestyle, to study various risk factors, including delayed first pregnancies and smaller number of pregnancies, and months of breast feeding; (c) chemoprevention, to identify chemical agents potentially able to inhibit the development of invasive cancer either by blocking the DNA damage that initiates carcinogenesis or by arresting or reversing the progression of premalignant cells. Different target populations for breast cancer chemoprevention may be recognized. Primary chemoprevention may involve a wide population of healthy women with a moderate risk due to nonpenetrant genetic factors (e.g., one first-degree relative with breast cancer) or exposure to known promoting agents (e.g., hormone replacement therapy). A second level of primary chemoprevention may involve a limited population at very high risk because of highly penetrating genetic predisposition to cancer (e.g., BRCA1 mutation carriers). Secondary chemoprevention may involve subjects with premalignant or early malignant lesions, e.g., breast atypical hyperplasia and carcinoma in situ or microinvasive disease. Prevention trials using clinical endpoints are always subject to high costs. Also, the risk of unexpected detrimental effects has recently been high-lighted, and much emphasis has been put on the search for intermediate, surrogate endpoints. Surrogate endpoints are biological markers that may be assessed or observed prior to the clinical appearance of the disease, bearing some relationship to the development of that disease. They are referred to as intermediate since they occur some time between a given intervention that affected the disease process and the time of the clinical diagnosis of the disease. The use of surrogate endpoint biomarkers in pivotal cancer chemoprevention trials may lead to a rational choice of agents which are likely to affect cancer incidence in subsequent phase III trials.

Biomarkers, Tumor↗
PubMed1998

Socioeconomic status and survival of gastric cancer patients.

Survival differences in cancer patients according to socioeconomic status (SES) have been reported for several organs, but the relationship with gastric cancer prognosis has not been conclusively defined. The present study analysed the survival of 122 incident, histologically confirmed gastric cancer patients diagnosed between 1985 and 1987 in Genoa, Italy and enrolled in a multicentric case-control study on gastric cancer occurrence and dietary habits. Adjusting for age at diagnosis, tumour stage, histopathological grading and surgery (i.e. curative gastric resection), Cox's proportional hazards regression model showed statistically significant hazard ratio (HR) (relative risk) estimates below unity for education (> 5 versus < or = 5 years of schooling, HR = 0.40, P = 0.003) and occupation (higher versus lower income job, HR = 0.59, P = 0.030). Also, the same final regression model revealed a positive prognostic effect for origin (Southern Italy migrants versus Genoa natives) (HR = 0.56, P = 0.039) and female gender (HR = 0.58, P = 0.020). High SES, origin from lower risk area for gastric cancer occurrence and female gender are positive prognostic categories for gastric cancer patients.

Adult↗
PubMed1998

Correlation between plasma transforming growth factor-beta 1 and second primary breast cancer in a chemoprevention trial.

The relationship between plasma transforming growth factor-beta 1 (TGF-beta 1) and second primary breast cancer was explored in a prevention trial of the synthetic retinoid fenretinide (N-(4-hydroxyphenyl)retinamide; 4-HPR). Plasma concentrations of TGF-beta 1 were measured by radioimmunoassay in plasma obtained at randomisation and after approximately 1 year of intervention in 28 women treated with 4-HPR and 27 untreated controls with stage I breast cancer. Baseline and 1 year growth factor concentrations were not significantly different between treated and control groups. After a median follow-up of 65 months, an increase in TGF-beta 1 over 1 year was the only significant, independent predictor of a shorter survival free from secondary primary breast cancer. Moreover, the change in TGF-beta 1 levels had a tendency to influence the treatment effect on second breast cancer incidence. Our data suggest that the role of plasma TGF-beta 1 as a surrogate endpoint of breast carcinogenesis should be assessed further.

Adult↗
PubMed1998

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines.

The potent mitogenic activity of insulin-like growth factor I (IGF-I) on breast epithelium is inhibited by retinoic acid in oestrogen receptor-positive (ER+) breast cancer cell lines. We studied and compared the effects of N-(4-hydroxyphenyl)-retinamide (4-HPR) in terms of growth inhibition and modulation of the IGF-I system in ER+ (MCF-7) and oestrogen receptor-negative (ER-) (MDA-MB231) breast cancer cell lines. Treatment with 1-10 microM 4-HPR for up to 96 h induced a dose- and time-dependent inhibition of proliferation in both breast cancer cell lines. Induction of apoptosis was much more evident in MCF-7 than in MDA-MB231 cells (30-40% compared with 0-5% respectively at 5 microM for 48 h). Exogenous human recombinant IGF-I (hr-IGF-I)-stimulated cell proliferation was abolished by 1 microM 4-HPR in MCF-7 cells. Immunoreactive IGF-I-like protein concentration in conditioned medium was reduced by 38% in MCF-7 and by 90% in MDA-MB231 cell lines following treatment for 48 h with 5 microM 4-HPR. Western ligand blot analysis showed a reduction of IGF-binding protein 4 (BP4) and BP5 by 67% and 87%, respectively, in MCF-7, whereas IGF-BP4 and -BP1 were reduced by approximately 20% in MDA-MB231 cells. Exposure to 5 microM 4-HPR for 48 h inhibited [125I]IGF-I binding and Scatchard analysis revealed a decrease of more than 50% in maximum binding capacity (Bmax) and a reduced receptor number/cell in both cancer cell lines. Steady-state type I IGF-receptor mRNA levels were reduced by approximately 30% in both tumour cell lines. We conclude that 4-HPR induces a significant down-regulation of the IGF-I system in both ER+ (MCF-7) and ER- (MDA-MB231) breast cancer cell lines. These findings suggest that, in our model, interference with the ER signalling pathway is not the only mechanism of breast cancer growth inhibition by 4-HPR.

Antineoplastic Agents↗
PubMed1998

Tamoxifen reduces plasma homocysteine levels in healthy women.

Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day(-1) or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no contraindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean +/- s.d. plasma levels of tHcy were 7.59 +/- 1.71 micromol l(-1), 7.25 +/- 1.61 and 7.09 +/- 1.33 in the tamoxifen group and 8.07 +/- 2.06, 7.93 +/- 1.77 and 8.12 +/- 2.04 in the placebo group at 0, 2 and 6 months (P = 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day(-1) for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction.

Adult↗
PubMed1998

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity.

Breast Neoplasms↗
PubMed1997

Long-term effects of fenretinide on retinal function.

The long-term effects of the synthetic retinoid fenretinide (4-HPR) on retinal function were studied by electroretinogram (ERG) in 24 women treated for a median of 30.5 months and in 18 untreated controls belonging to a phase III intervention trial. The six outcome measures were: a wave implicit time, peak-to-peak amplitude and implicit time of b wave following both cone stimulation and maximal cone-rod stimulation in the dark-adapted eye. Multivariate analysis of covariance was applied to evaluate the joint effect on the whole set of ERG measures taking into account their inter-relationship. Predictive factors with a significant effect on ERG measures were: (1) a qualitative interaction between age and treatment duration and (2) the squared (parabolic) function of plasma retinol. Individually, the b wave implicit time following cone stimulation was the only ERG measure significantly influenced by the predictors, indicating a primary effect of 4-HPR on retinal photoreceptor sensitivity without significant alterations of the inner nuclear layer. Thus, in contrast to previous reports at higher dose, administration of 4-HPR at 200 mg/day seems to exert subtle alterations of retinal function as measured by ERG.

Age Factors↗