Self-rated quality of life measures: effect of change to a low-fat, high-fiber, fruit and vegetable enriched diet.

The Polyp Prevention Trial (PPT) was a multicenter, randomized clinical trial to determine the effect of a low-fat (20% of energy from fat), high-fiber (18 g/1,000 kcal/day), high-fruit/vegetable (3.5 servings/1,000 kcal/day) eatingplan on the recurrence of large bowel adenomatous polyps. The PPT provided an opportunity to examine the impact of dietary changes on quality of life. At baseline and annuallyfor 4 years, participants in the Quality of Life Substudy of PPT completed a Quality of Life Factors (QF) Questionnaire, a modified Block-National Cancer Institute Food Frequency Questionnaire, and a Health and Lifestyle Questionnaire. The 51-item QF Questionnaire assessed changes in nine domains: taste, convenience, cost, self-care, social, health assessment, health belief health action, and life satisfaction. The analysis compared annual changes in domain scores for intervention (n = 194) and control (n = 200) participants. At Year 1, 363 (92%) completed a questionnaire, and 325 (82%) participants completed a Year 4 questionnaire. There were no statistically significant differences between treatment groups in the change from baseline to Year 1 for the convenience, cost, taste, health assessment, and life satisfaction domains. At Year 1, intervention participants rated the self-care (p < .001), health belief (p = .021), and health action (p < .001) domains significantly higher and the social domain significantly lower (p <.001) than control participants. These changes were consistent through Years 2, 3, and 4. This study

Serum hormones and the alcohol-breast cancer association in postmenopausal women.

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.

Measuring cell proliferation in the rectal mucosa. comparing bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) assays.

Cell proliferation in the human colorectum can be measured using bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA) assays. Using data from the National Cancer Institute's Polyp Prevention Trial, these two assays are compared using correlation coefficients and variance components analysis. Adjusting for fixed as well as for the random effects of between-biopsy and scoring variation, the estimated correlation is 0.46 for the log labeling index and 0.45 for log proliferative height. This is an estimate of the highest correlation that can be achieved by taking multiple biopsies scored by multiple scorers. For single biopsies, the estimated correlation is 0.16 and 0.10, respectively. There are significant differences between the variance components for the two assays. For example, for log labeling index, PCNA has a lower variation between biopsies than BrdU, but higher variation between scorings. When used in a clinical or epidemiological setting, it is important to take multiple biopsies at multiple time points.

An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial: can we detect informative differences among individuals' proliferation measures amid the noise?

We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U. S. National Cancer Institute's multicenter Polyp Prevention Trial. Biopsies were blindly double-scored by two technicians. For those participants for whom at least one evaluable biopsy was obtained, a mean of 2.0 and 2.6 biopsies, and 6.2 and 8.7 crypts/biopsy were evaluated, respectively, with the BrdUrd and PCNA assays. Factors such as clinical center, scorer, and month of biopsy collection significantly affected the observed values of the labeling index (LI) and proliferative height (PH). Therefore, it is essential to control or adjust for these variables in proliferation studies. Sources of random variation for LI and PH measures remaining after the aforementioned factors include between-participant variation and several sources of within-participant variation, including variation over time, between biopsies, and between multiple measurements on the same biopsy. Both LI and PH measurements exhibited substantial variability over time, between biopsies, and from reading-to-reading of the same biopsy. When other sources of variability have been accounted for, the PCNA LI seems to have little between-participant variation. This brings into question its utility as a marker in colorectal cancer studies. The PCNA PH showed significant between-participant variability and may hold some promise as a useful marker in colorectal cancer studies. Results for BrdUrd were less conclusive. The BrdUrd LI showed marginally significant between-participant variation, whereas the corresponding variation for PH was nonsignificant.

A Voluntary Smokers' Registry: Characteristics of joiners and non-joiners in the Community Intervention Trial for Smoking Cessation (COMMIT).

OBJECTIVES: This paper examines differences between joiners and nonjoiners of a voluntary smokers' registry. METHODS: A baseline prevalence survey was used to identify characteristics of smokers who joined or did not join a smokers' registry. RESULTS: Communities varied significantly in registry enrollment rates. Heavy-smoking joiners expressed more desire to quit, were more likely to live with nonsmokers, and were older than nonjoiners. Light-to-moderate joiners smoked more, were more addicted to cigarettes, and expressed more desire to quit than nonjoiners. CONCLUSIONS: Few baseline characteristics differentiated joiners from nonjoiners. Nonjoiners were significantly more likely to achieve cessation than joiners.

Community Intervention Trial for Smoking Cessation (COMMIT): changes in community attitudes toward cigarette smoking.

The success of the Community Intervention Trial for Smoking Cessation (COMMIT) in changing smoking attitudes is examined by testing two primary hypotheses: (1) the priority of smoking as a public health problem increased more in the intervention communities than in the comparison communities, and (2) norms and values that support non-smoking increased more in the intervention than in the comparison communities. One community within each of 11 matched pairs was randomly assigned to receive a 4-year (1989-92) community-based smoking control intervention. Community attitudes towards smoking were measured primarily by cross-sectional surveys in 1989 (n = 9875) and 1993 (n = 14117) but a cohort (n = 5450) also provided attitude information. The main trial effect was on heavy smokers in the intervention communities who showed significantly more change in their beliefs about smoking as a public health problem. Despite the absence of an intervention-comparison difference, the magnitude of change in community-wide norms and values was related to the level of smoking control activities. In the cohort, light-to-moderate smokers in the intervention communities came to have stronger beliefs about smoking as a serious public health problem. COMMIT's impact on the beliefs of heavy smokers about the seriousness of smoking as a public health problem has important public health implications.

The efficiency of the matched-pairs design of the Community Intervention Trial for Smoking Cessation (COMMIT).

The Community Intervention Trial for Smoking Cessation (COMMIT) was a randomized trial to evaluate the effects of a community-wide smoking cessation intervention on smoking behavior. The statistical design involved 22 pair-matched communities and the randomization of one community in each of the 11 pairs to the intervention, with the other community in the pair acting as a comparison. Communities were matched on the basis of their geographical proximity and similarity of demographic composition. In this paper, we use the data on the rates of quitting smoking among cohorts of heavy and light/moderate smokers in each community to estimate the gains in efficiency achieved by the matched-pairs design compared to an unmatched randomized trial. We find evidence of some gain in efficiency, although the data are not extensive enough to give estimates of efficiency gain that have good precision.

Interplay between design and analysis for behavioral intervention trials with community as the unit of randomization.

This paper outlines an approach for the design and analysis of randomized controlled trials investigating community-based interventions for behavioral change aimed at health promotion. The approach is illustrated using the Community Intervention Trial for Smoking Cessation (COMMIT), conducted from 1988 to 1993, involving 11 pairs of communities in North America, matched on geographic location, size, and sociodemographic factors. The situation discussed is when assignment to intervention is done at the community level; for COMMIT, the very nature of the intervention required this. The number of communities as a key determinant of the statistical power of the trial. The use of matched pairs of communities can achieve a gain in statistical efficiency. Randomization is used to obtain an unbiased assessment of the intervention effect; randomization also provides the basis for statistical analysis. Permutation tests (and corresponding test-based confidence intervals), using community as the unit of analysis, follow directly from the randomization distribution. Within this framework, individual-level covariates can be used for imputation of missing values and for adjusting analyses of intervention effect.

Radical prostatectomy versus expectant treatment for early carcinoma of the prostate. Twenty-three year follow-up of a prospective randomized study.

In a study by the Veterans Administration Cooperative Urological Research Group (VACURG), 142 patients with localized prostate cancer, VACURG stage I and II, were randomized between radical prostatectomy plus placebo versus placebo alone as initial treatment. 111 patients were evaluable for treatment comparison. Median follow-up for survival is 23 years. The prognostic value of Gleason histologic grading was confirmed. A difference in overall survival in favor of radical prostatectomy was observed in stage I patients. However, after adjustment for imbalance in age distribution, no statistically significant differences in survival could be demonstrated in either stage or in both stages combined. The results are discussed considering the small sample size and the limited statistical power of the study.

Aspects of statistical design for the Community Intervention Trial for Smoking Cessation (COMMIT).

We present statistical considerations for the design of the Community Intervention Trial for Smoking Cessation (COMMIT). One outcome measurement, the quit rate in randomly selected cohorts of smokers, is compared with another outcome measurement, the decrease in smoking prevalence, in terms of statistical efficiency and interpretability. The COMMIT study uses both types of outcome measurements. The merits of pair-matching the communities are considered, and sample size calculations take into account heterogeneity among pair-matched communities. In addition to significance tests based on the permutational (randomization) distribution, we also describe approaches for covariate adjustment. The COMMIT design includes 11 pair-matched communities, which should provide good power to detect a 10% or greater difference in quit rates between the intervention and control communities in cohorts of heavy smokers and in cohorts of light or moderate smokers. The power is only moderate to detect intervention effects on the decreases in overall smoking prevalence or in the prevalence of heavy smoking.

Radical prostatectomy versus expectant primary treatment in stages I and II prostatic cancer. A fifteen-year follow-up.

A fifteen-year follow-up of a prospective, randomized study comparing placebo with radical prostatectomy as the primary treatment of early prostatic cancer is presented. A total of 111 patients with clinical Stage I or II prostatic cancer, normal acid phosphatase levels, and negative findings on skeletal x-ray film were evaluable. Thirty Stage I patients and 20 Stage II patients received placebo only; 31 Stage I and 30 Stage II patients underwent radical prostatectomy. The survival status for 95 patients (86%) was established at the fifteen-year follow-up. No significant differences in crude survival occurred in either stage or in both stages combined. Moreover, the survival curves closely followed reference curves based on expected U.S. mortality for men of comparable ages and races. A statistically significant association between a high Gleason histologic score and poor survival was established. In this study, initial treatment with radical prostatectomy did not yield longer survival than initial placebo treatment alone. However, the findings should be interpreted with caution, since sample size was small and staging procedure was simplified.

Projecting individualized probabilities of developing breast cancer for white females who are being examined annually.

To assist in medical counseling, we present a method to estimate the chance that a woman with given age and risk factors will develop breast cancer over a specified interval. The risk factors used were age at menarche, age at first live birth, number of previous biopsies, and number of first-degree relatives with breast cancer. A model of relative risks for various combinations of these factors was developed from case-control data from the Breast Cancer Detection Demonstration Project (BCDDP). The model allowed for the fact that relative risks associated with previous breast biopsies were smaller for women aged 50 or more than for younger women. Thus, the proportional hazards models for those under age 50 and for those of age 50 or more. The baseline age-specific hazard rate, which is the rate for a patient without identified risk factors, is computed as the product of the observed age-specific composite hazard rate times the quantity 1 minus the attributable risk. We calculated individualized breast cancer probabilities from information on relative risks and the baseline hazard rate. These calculations take competing risks and the interval of risk into account. Our data were derived from women who participated in the BCDDP and who tended to return for periodic examinations. For this reason, the risk projections given are probably most reliable for counseling women who plan to be examined about once a year.

A prospective study of the development of breast cancer in 16,692 women with benign breast disease.

The authors studied the relation between benign breast disease and subsequent breast cancer in 16,692 women with biopsy-diagnosed benign breast disease who had participated in the Breast Cancer Detection Demonstration Project throughout the United States. Women were classified into one of five benign breast disease categories: atypical hyperplasia, proliferative disease without atypia, nonproliferative disease, fibroadenoma, and other benign breast disease. A total of 485 incident cases of breast cancer were identified in the women from August 1973 to February 1986 after a median follow-up period of 8.3 years from the diagnosis of benign breast disease. Age-adjusted incidence rates were calculated for benign breast disease types stratified by family history and calcification status. Relative risk (RR) estimates of breast cancer for women in the five benign breast disease categories, compared with the screened women who did not develop recognizable breast disease (normal subjects), were computed using the proportional hazards model. Results indicated that risk was associated with the degree of epithelial atypia. Over all age groups, women with nonproliferative disease, proliferative disease without atypia, and atypical hyperplasia displayed progressively increasing risks of 1.5, 1.9, and 3.0, respectively, compared with normal subjects, with 95% confidence intervals (CI) exceeding unity. Particularly high risk was seen among women under age 46 years with atypical hyperplasia (RR = 5.7, 95% CI 3.0-10.6). Women with fibroadenoma as the only indication of their benign breast disease had a relative risk of 1.7, with a lower 95% confidence limit of 1.0. No increased risk was seen for women with other benign breast disease. Positive family history (RR = 1.8) and calcification (RR = 1.2) significantly increased a woman's risk proportionately over the risk associated with each benign breast disease subtype. The authors conclude that the risk of developing breast cancer varies by category of benign breast disease and is directly related to the degree of epithelial atypia.

Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies.

Between 1960 and 1975, the Veterans Administration Cooperative Urological Research Group conducted a consecutive series of 3 major randomized clinical trials comparing various endocrine treatments for newly diagnosed prostate cancer patients. Six major conclusions concerning hormonal treatment emerged from these studies: 1) increased hazard of cardiovascular death after therapy with 5 mg diethylstilbestrol (DES); 2) orchiectomy plus DES no better than orchiectomy or DES alone; 3) equivalent effect of 1.0 and 5.0 mg DES on cancer; 4) reduced cardiovascular hazard from therapy with 1.0 mg DES; 5) Premarin and Provera no better than 1.0 mg DES at doses studied; 6) decisions about hormone treatment at diagnosis dependent on patient characteristics, mainly age and Gleason grade. In this paper, these studies are reviewed briefly and data are presented to support these conclusions. Some tentative treatment recommendations are proposed.

Relationship of quantitative estrogen-receptor level and clinical response to cytotoxic chemotherapy in advanced breast cancer. An extramural analysis.

Three hundred twenty-four patients with advanced breast cancer from seven institutions whose x-rays and records had been externally reviewed for evidence of objective regression of disease were again reviewed, this time regarding their responses to chemotherapy in relationship to estrogen receptor (ER) levels. Higher levels of ER were found in older or postmenopausal women, in those with longer disease-free intervals or with osseous metastasis, and in women whose chemotherapy treatment was given later relative to first recurrence of disease. Response to chemotherapy in 60%, or 194 cases, was comparable to the response rate in other patients treated with the same drugs. Patients with ER levels greater than 3 fmoles/mg cytosol protein had a response rate of 67% and 58% of patients with ER less than 3 fmoles responded. Regimens containing Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) in combination appeared to give higher response rates. Addition of vincristine or prednisone did not improve response rates. The best response rate (88%) was in 16 patients who had ER levels in excess of 50 fmoles and received four or more drugs. There appeared to be a benefit from increased number of drugs and from quantitatively high ER levels. There is a discussion of the possible implication of these findings.