Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14.

BACKGROUND: Tamoxifen is advantageous in treating all stages of breast cancer. However, studies have suggested that incidence and severity of endometrial cancer increase in women treated with tamoxifen. PURPOSE: We compared rates of endometrial and other cancers in tamoxifen- and non-tamoxifen-treated patients and described the pathologic characteristics of the endometrial cancers. METHODS: Data were analyzed on 2843 patients with node-negative, estrogen receptor-positive, invasive breast cancer randomly assigned to placebo or tamoxifen (20 mg/d) and on 1220 tamoxifen-treated patients registered in NSABP B-14 subsequent to randomization. Average time on study is 8 years for randomly assigned patients and 5 years for registered patients. RESULTS: The incidence rates of liver, gastrointestinal, urinary tract, and nonuterine genital tumors were not increased by tamoxifen treatment. Twenty-five endometrial cancers were originally reported, one of which was reclassified after subsequent review. Two cases occurred in the placebo group in patients whose medical status subsequent to random assignment had required tamoxifen treatment. Twenty-three occurred in the tamoxifen groups. Twenty-one of the 24 originally reported endometrial cancers were FIGO stage 1; 18 of 23 gradable cases were of good to moderate histologic grade. Four tamoxifen-treated women died of uterine cancer. The average annual hazard rate of endometrial cancer as a first event within the first 5 years of follow-up in the randomized, tamoxifen-treated group was 1.2/1000 patient-years; the cumulative hazard rate was 6.3/1000. Findings for the registered, tamoxifen-treated group were similar. Including all originally reported endometrial cancers, the annual hazard rate through all follow-up was 0.2/1000 in the placebo group and 1.6/1000 in the randomized, tamoxifen-treated group; the relative risk of endometrial cancer for the latter versus the former group was 7.5. Again for the latter group, using population-based rates of endometrial cancer from SEER data and information from another NSABP (B-06) trial, relative risks were 2.2 and 2.3, respectively. The 5-year cumulative hazard rate for disease-free survival in the randomized tamoxifen group was 38% less than that in the placebo group. Some data in this paper were provided by an investigator who submitted fraudulent data to the NSABP [see the "News" section]; therefore, the reader must read the entire text including Table 10 and the Editor's notes. In brief, data on 182 of the 2843 randomly assigned patients and 37 of the 1220 registered patients were provided by the investigator in question. After review, 24 of the 182 records showed falsification, all involving characteristics of patients prior to random assignment. Of the 37 registered-patient records, 8 showed falsification. CONCLUSIONS: Risk of endometrial cancer increases following tamoxifen therapy for invasive breast cancer; however, net benefit greatly outweighs risk. Endometrial cancers occurring after tamoxifen therapy do not appear to be of a different type with a worse prognosis than are such tumors in non-tamoxifen-treated patients. IMPLICATIONS: Tamoxifen treatment for breast cancer should continue. In addition, the relative risk of endometrial cancer observed in B-14 tamoxifen-treated patients is consistent with the twofold relative risk used in the initial risk-benefit computation for the NSABP breast cancer prevention trial.

Lipid levels in adults with cystic fibrosis.

OBJECTIVE: To examine the hypothesis that an energy-dense, high-fat diet, which is necessary to maintain weight in adults with cystic fibrosis, does not result in high serum cholesterol levels. DESIGN: Dietary, anthropometric, and biochemical data were correlated. SETTING: A cystic fibrosis center in Pittsburgh, Pa. SUBJECTS: Thirty-one adults with cystic fibrosis, 50 obligate carriers of the cystic fibrosis gene, and 26 controls who did not have cystic fibrosis. MAIN OUTCOME MEASURES: Adults with cystic fibrosis had a lower mean serum cholesterol level and higher mean intakes of energy and fat than controls. STATISTICAL ANALYSES PERFORMED: Student's t test was used to determine the statistical significance between two means. Univariate correlation coefficients were determined to measure the relative intensity of association between two variables. RESULTS: Mean total serum cholesterol levels in men with cystic fibrosis was 3.1 mmol/L vs 4.7 mmol/L in male controls (P < .001). Mean total serum cholesterol levels in women with cystic fibrosis was 3.2 mmol/L vs 4.3 mmol/L in female controls (P < .001). Three adults with cystic fibrosis and no signs of pancreatic insufficiency had serum cholesterol levels in the high normal range. Carriers had serum lipid levels in the same range as the controls. CONCLUSIONS/APPLICATIONS: The findings indicate that a high-energy, high-fat diet does not raise serum lipid levels in those patients with cystic fibrosis and pancreatic insufficiency. However, those individuals with cystic fibrosis and normal pancreatic function may be at the same risk as the general population for developing high serum lipid levels. They should have their serum lipid levels monitored and be given appropriate dietary recommendations.

Evidence of an altered pattern of breathing during exercise in recipients of heart-lung transplants.

Recipients of heart-lung transplants represent an unusual opportunity to study the regulation of ventilation, because the neural pathways between the lungs and the central nervous system are disrupted in these patients. We compared the ventilation response in seven recipients of heart-lung transplants who had normal pulmonary function and seven recipients of heart transplants, all of whom performed incremental bicycle ergometry. The level of ventilation in recipients of heart-lung transplants was similar to that in heart-transplant recipients for equivalent levels of carbon dioxide production. Arterial pH and partial pressure of carbon dioxide at maximal exercise were normal and not significantly different in the two groups, also suggesting that levels of ventilation were appropriate in both groups. However, the rate of the rise in respiratory rate for increasing levels of ventilation was significantly lower in recipients of heart-lung transplants than in heart-transplant recipients, and the initial increase in tidal volume was more rapid in the former group than in the latter. Thus, recipients of heart-lung transplants have an appropriate level of ventilation during exercise as the result of a disproportionate increase in tidal volume at a reduced respiratory rate. We speculate that intrapulmonary receptors are important in regulating the pattern, but not the absolute level, of ventilation during exercise.

A multistage approach to the cohort analysis of lifetime lung cancer risk among steelworkers exposed to coke oven emissions.

A cohort analysis was performed to predict the lifetime lung cancer risk to a US or Canadian nonwhite male steelworker exposed to coke oven emissions. The procedure employed required that the lung cancer mortality (used for risk assessment) be estimated by addition of the excess to the background rates. The age-specific excess rates were obtained following selection of the proper excess risk function as implied by the multistage theory of carcinogenesis. A quantitative approach based on model fitting was used for selection of the excess risk function. The results show no evidence that coke oven emissions have a late stage carcinogenic effect. The indication that the agent acts as an initiator is moderate to weak. The number of carcinogenic stages involved was estimated to be four. Based on the assumption that exposure was set at a high concentration for 40 years with a starting age of 20 years, it was estimated that the lifetime risk through age 85+ years for a hypothetical US or Canadian nonwhite male oven worker could be as high as 0.40. This represents a 15-fold increase of the baseline risk.