Search PubMed⌕ Search

Biomedical subjects

N F Boyd

Publications and source records attributed to N F Boyd.

At least 37 records · Page 2Linked to original sources
PubMed1998

Serum leptin levels and energy expenditure in normal weight women.

To investigate whether circulating leptin levels are associated with energy expenditure in healthy humans, doubly labeled water energy measurements and food intake assessment were carried out in 27 women (mean age, 48.6 years; weight, 61.9 kg; body mass index, 23.2). Energy expenditure was determined over 13 days. Food intake was measured by 7-day food records. Leptin was measured by radioimmunoassay. Leptin level was strongly associated with percentage body fat (r = 0.59; p < 0.001), fat mass (r = 0.60; p < 0.001), and body mass index (r = 0.41; p = 0.03), but no correlation was observed with energy expenditure (r = 0.02; p = 0.93). After controlling for percentage body fat, a positive association of leptin level with energy expenditure of marginal significance (p = 0.06) was observed. There were no significant univariate associations of age, physical activity, lean body mass, height, or dietary variables with leptin level. When controlling for body fat, a significant positive correlation was observed for percent energy from carbohydrate and negative correlations with dietary fat and alcohol intake. These findings confirm previous associations between leptin and body fat content and suggest a relationship between serum leptin and energy expenditure level in healthy humans.

Body Weight↗
PubMed1998

Mammographic densities and breast cancer risk.

The radiological appearance of the female breast varies among individuals because of differences in the relative amounts and X-ray attenuation characteristics of fat and epithelial and stromal tissues. Fat is radiolucent and appears dark on a mammogram, and epithelium and stroma are radiodense and appear light. We review here the evidence that these variations, known as mammographic parenchymal patterns, are related to risk of breast cancer. Studies that used quantitative measurement to classify mammographic patterns have consistently found that women with dense tissue in more than 60-75% of the breast are at four to six times greater risk of breast cancer than those with no densities. These risk estimates are independent of the effects of other risk factors and have been shown to persist over at least 10 years of follow up. Estimates of attributable risk suggest that this risk factor may account for as many as 30% of breast cancer cases. Mammographically dense breast tissue is associated both with epithelial proliferation and with stromal fibrosis. The relationship between these histological features and risk of breast cancer may by explained by the known actions of growth factors that are thought to play important roles in breast development and carcinogenesis. Mammographically dense tissue differs from most other breast cancer risk factors in the strength of the associated relative and attributable risks for breast cancer, and because it can be changed by hormonal and dietary interventions. This risk factor may be most useful as a means of investigating the etiology of breast cancer and of testing hypotheses about potential preventive strategies.

Breast↗
PubMed1997

Automated analysis of mammographic densities and breast carcinoma risk.

BACKGROUND: There is considerable evidence that one of the strongest risk factors for breast carcinoma can be assessed from the mammographic appearance of the breast. However, the magnitude of the risk factor and the reliability of the prediction depend on the method of classification. Subjective classification requires specialized observer training and suffers from inter- and intraobserver variability. Furthermore, the categoric scales make it difficult to distinguish small differences in mammographic appearance. To address these limitations, automated analysis techniques that characterize mammographic density on a continuous scale have been considered, but as yet, these have been evaluated only for their ability to reproduce subjective classifications of mammographic parenchyma. METHODS: In this study, using a nested case-control design, the authors evaluated the direct association between breast carcinoma risk and quantitative image features derived from automated analysis of digitized film mammograms. Two parameters, one describing the distribution of breast tissue density as reflected by brightness of the mammogram (regional skewness) and the other characterizing texture (fractal dimension), were calculated for images from 708 subjects identified from the Canadian National Breast Screening Study. RESULTS: These parameters were evaluated for their ability to distinguish cases (those women who developed breast carcinoma) from controls. It was found that both the skewness and fractal parameters were significantly related to risk of developing breast carcinoma. CONCLUSIONS: Although the relative risk estimates were moderate (typically > 2.0) and less than those from subjective classification or for an interactive computer method the authors have previously described, they are comparable to other risk factors for the disease. The observer independence and reproducibility of the automated methods may facilitate their more widespread use.

Adult↗
PubMed1997

Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group.

BACKGROUND: The appearance of breast tissue on mammography varies according to its composition. Fat is radiolucent and appears dark on mammography, while stromal and epithelial tissue has greater optical density and appears light. Extensive areas of radiologically dense breast tissue seen on mammography are associated with an increased risk of breast cancer. PURPOSE: The purpose of the present study was to determine whether the adoption of a low-fat, high-carbohydrate diet for 2 years would reduce breast density. METHODS: Women with radiologic densities in more than 50% of the breast area on mammography were recruited and randomly allocated to an intervention group taught to reduce intake of dietary fat (mean, 21% of calories) and increase complex carbohydrate (mean, 61% of calories) or to a control group (mean, 32% of calories from fat and 50% of calories from carbohydrates). Mammographic images from 817 subjects were taken at baseline and compared with those taken 2 years after random allocation by use of a quantitative image analysis system, without knowledge of the dietary group of the subjects or of the sequence in which pairs of images had been taken. The effects of the intervention on the mammographic features of breast area, area of dense tissues in the breast, and the percent of the breast occupied by dense tissue were examined using t tests. Multiple regression was used to examine these effects while accounting for age at trial entry, weight change, and menopausal status. RESULTS: After 2 years, the total area of the breast was reduced by an average of 233.7 mm2 (2.4%) (95% confidence interval [CI] = 106.9-360.6) in the intervention group compared with an average increase of 26.3 mm2 (0.3%) (95% CI = -108.0-160.5) in the control group (P = .01). The area of density was reduced by 374.4 mm2 (6.1%) (95% CI = 235.1-513.8) in the intervention group compared with an average of 127.7 mm2 (2.1%) (95% CI = 8.6-246.7) in the control group (P = .01). Weight loss was associated with a reduction in breast area. The effect of the intervention on breast area was only marginally statistically significant after weight change, menopausal status, and age at trial entry were taken into account (P = .06). Greater weight loss and becoming postmenopausal were associated with statistically significant reductions in the area of density on the mammographic image at 2 years (P = .04 and P<.001, respectively). Age at entry into the trial was marginally significant in the same direction (P = .06). The effect of the intervention on area of density remained statistically significant after controlling for weight loss, age at entry, and menopausal status (P = .03). The change in the percentage of dense tissue in the mammographic image was not significantly different between the two groups (P = .71). CONCLUSIONS AND IMPLICATIONS: These results show that after 2 years, a low-fat, high-carbohydrate diet reduced the area of mammographic density, a radiographic feature of the breast that is a risk factor for breast cancer. Longer observation of a larger number of subjects will be required to determine whether these effects are associated with changes in risk of breast cancer.

Adult↗
PubMed1997

The review of randomization in the Canadian National Breast Screening Study. Is the debate over?

The randomization procedure in the Canadian National Breast Screening Study (NBSS) is assessed in this issue (see pages 193 to 199) by Drs. John C. Bailar III and Brian MacMahon. They conclude that although there was ample opportunity for the randomization process to be subverted, no evidence of subversion was found. This is unlikely to allay all concerns about randomization, because there are still puzzling differences between the arms of the NBSS in a number of baseline variables. For example, the existence of prior health claims for breast cancer for women who entered the NBSS in Manitoba has raised the possibility that subversion occurred. Although the question may never be resolved, one lesion is clear: randomization in clinical trials should be managed in a manner that makes subversion impossible. As for the clinical implications of the NBSS for women in their 40s, physicians may now look to the results of randomized trials that have been published more recently. A meta-analysis of these results suggests that screening mammography reduces deaths from breast cancer among women in their 40s, but continued follow-up over the next few years will be needed to settle the debate.

Adult↗
PubMed1997

Assessment of a food frequency questionnaire as a screening tool for low fat intakes.

This study tested the ability of a self-administered food frequency questionnaire (FFQ) to identify women with low fat intakes. FFQs were completed by 95 control participants of a dietary trial at a mean 2.9 +/- 0.8 years post-randomization. Subjects were selected in approximately equal numbers from women who were low-fat eaters (< or = 30% of energy from fat) and high-fat eaters (> 30% of energy from fat). Percentage energy from fat derived from food records and FFQ were similar in both the low- and high-fat eaters. Percentage of energy from carbohydrate and total grams of carbohydrate (low-fat eaters only) were slightly higher measured by FFQ than by food records, and percentage of energy from protein was slightly lower. The correlation between nutrient intake measured by FFQ and food records for the whole group was 0.74 for percentage of energy from fat, 0.50 for total fat, 0.59 for percentage of energy from carbohydrate, 0.43 for total carbohydrate, 0.53 for percentage of energy from protein, 0.27 for total protein, and 0.32 for energy intake. Correlations were slightly lower when the low- and high-fat eaters were examined separately. The area under the receiver operating characteristic (ROC) curve, 0.83, was significantly above 0.5 (p < < 0.001), indicating that the FFQ discriminated between low- and high-fat eaters significantly better than chance. The FFQ cutoff point of 30% of energy from fat had a true positive rate of 0.63 and false positive rate of 0.24. The use of this cutoff point for screening would result in the loss of 36% of potential subjects and an estimated increase in baseline percentage of energy from fat intake of 2.3 percentage points.

Adult↗
PubMed1997

Feasibility of obtaining breast epithelial cells from healthy women for studies of cellular proliferation.

Increased dietary fat intake and rate of breast epithelial cell proliferation have each been associated with the development of breast cancer. The goal of this study was to measure the effect of a low fat, high carbohydrate diet on the rate of breast epithelial cell proliferation in women at high risk for breast cancer. Women were recruited from the intervention and control groups of a randomized low fat dietary intervention trial, breast epithelial cells were obtained by fine needle aspiration, and cell proliferation was assessed in these samples using immunofluorescent detection of Ki-67 and PCNA. The effects of needle size and study group on cell yield and cytologic features of the cells were also examined. Fifty three women (20 in the intervention group and 33 in the control group) underwent the biopsy procedure. Slides from 38 subjects were stained for Ki-67 and from 14 subjects for PCNA. No cell proliferation (fluorescence) was detected for either Ki-67 or PCNA in any of the slides. Epithelial cell yield and number of stromal fragments were greater with a larger needle size. Numbers of stromal fragments and bipolar naked nuclei were greater in the low fat as compared to the control group but no differences in epithelial cell yield were observed between the two groups. This study confirms that fine needle aspiration biopsy is a feasible method of obtaining epithelial cells from women without discrete breast masses, but suggests that cell proliferation cannot be assessed using Ki-67 and PCNA in such samples.

Biomarkers↗
PubMed1997

Effects of a low-fat high-carbohydrate diet on plasma sex hormones in premenopausal women: results from a randomized controlled trial. Canadian Diet and Breast Cancer Prevention Study Group.

We are conducting a long-term randomized controlled trial to determine if intervention with a low-fat high-carbohydrate diet reduces breast cancer risk. The present study examines the effects of 2 years of dietary intervention on serum sex hormone levels in premenopausal women. Subjects with extensive mammographic densities were enrolled in a dietary intervention trial. The intervention involved intensive individual counselling aimed at reducing total dietary fat to 15% of calories. Control subjects received general advice about diet but were not counselled to change their fat intake. Serum sex hormone levels were measured in 220 premenopausal subjects at entry and 2 years after randomization. Two years after randomization oestradiol levels were 20% (70 pmol l(-1)) lower (P = 0.04) and progesterone levels were 35% (1.0 nmol l(-1)) lower (P = 0.004) and follicle-stimulating hormone (FSH) levels were 7% (1 IU) higher (P = 0.38) in the intervention group than in the control group. The FSH-oestradiol ratio was 13% higher in the intervention group (P = 0.18). Samples analysed accounting for the timing of the blood sample in relation to the menstrual cycle showed that, in the intervention group, oestradiol and progesterone levels were lower and FSH levels higher in subjects with blood samples taken more than 30 days after the last menstrual period. Because of the strong evidence linking ovarian hormonal activity to breast cancer risk, these results suggest that a low-fat high-carbohydrate diet may reduce risk of breast cancer by reducing exposure to ovarian hormones that are a stimulus to cell division in the breast.

Adult↗
PubMed1997

Elevated levels of plasma triglycerides are associated with histologically defined premenopausal breast cancer risk.

Lipids and lipoproteins have been associated with breast cancer risk; however, published results have been inconsistent. To clarify these associations, we measured fasting lipids in women undergoing breast biopsies. A case-control study examined the association of fasting levels of lipids with histologically defined breast cancer risk. Four groups of premenopausal women were assembled on the basis of histological appearance of breast tissue: 1) no epithelial proliferation (n = 102), 2) proliferation without atypia (n = 53), 3) atypical hyperplasia or carcinoma in situ (n = 53), and 4) node-negative invasive cancer (n = 102). A postoperative fasting blood specimen was analyzed for cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Demographics, risk factors, diet, physical activity, fasting weight, and skin-fold thickness were measured. Triglyceride levels were significantly higher in women with node-negative invasive cancer (0.94 +/- 1.04 mg/ml) than in those with no epithelial proliferation (0.83 +/- 1.04 mg/ml, p = 0.03). This association persisted after adjustment for age, body size, lipids, reproductive and familial risk factors, and previous benign breast problems (p < 0.01), in keeping with an independent association of elevated triglycerides with breast cancer risk.

Adult↗
PubMed1996

Quantitative correlation of breast tissue parameters using magnetic resonance and X-ray mammography.

Previous investigators have shown that there is a strong association between the fraction of fibroglandular tissue within the breast as determined by X-ray mammography (per cent density) and breast cancer risk. In this study, the quantitative correlation between per cent density and two objective magnetic resonance (MR) parameters of breast tissue, relative water content and mean T2 relaxation time, as investigated for 42 asymptomatic subjects. Using newly developed, rapid techniques MR measurements were performed on a volume-of-interest incorporating equal, representative portions of both breasts. X-ray mammograms of each subject were digitised and analysed semiautomatically to determine per cent density. Relative water content showed a strong positive correlation with per cent density (Pearson correlation coefficient rp = 0.79, P < 0.0001) and mean T2 value showed a strong negative correlation with per cent density (rp = -0.61, P < 0.0001). The MR and X-ray parameters were also associated with sociodemographic and anthropometric risk factors for breast cancer (P < 0.05). The potential use of MR parameters to assess risk of breast cancer and to provide a frequent, non-hazardous monitor of breast parenchyma is discussed.

Adipose Tissue↗
PubMed1996

Automated analysis of mammographic densities.

Information derived from mammographic parenchymal patterns provides one of the strongest indicators of the risk of developing breast cancer. To address several limitations of subjective classification of mammographic parenchyma into coarse density categories, we have been investigating more quantitative, objective methods of analysing the film-screen mammogram. These include measures of the skewness of the image brightness histogram, and of image texture characterized by the fractal dimension. Both measures were found to be strongly correlated with radiologists' subjective classifications of mammographic parenchyma (Spearman correlation coefficients, Rs = -0.88 and -0.76 for skewness and fractal dimension measurements, respectively). Further, neither measure was strongly dependent on simulated changes in mammographic technique. Correlation with subjective classification of mammographic density was better when both the skewness and fractal measures were used in combination than when either was used alone. This suggests that each feature provides some independent information.

Adult↗
PubMed1996

Comparison of energy intakes determined by food records and doubly labeled water in women participating in a dietary-intervention trial.

The accuracy of estimates of usual energy intake derived from food records in participants of a long-term dietary-intervention trial was studied in a subset of 29 women aged 48.7+/-5.0 y and weighing 61.9+/-6.5 kg. This sample was similar to the population in the whole trial (n=715), from which it was selected in terms of age, weight, body mass index (BMI), and reported energy and fat intakes. During the validation study, reported energy intake was derived from 7 consecutive days of food records, and total energy expenditure was measured by the doubly labeled water method over 13 d. Reported energy intake (6.98+/-1.58 MJ/d) was significantly lower than energy expenditure (9.00+/-2.08MJ/d) and represented 79.8+/-17.6% of expenditure. The correlation between reported energy intake and expenditure was 0.46 (P=0.01, 95% CI: 0.15, 0.71). Body weight, BMI, height, length of time in the dietary trial, and percentage of energy from fat and carbohydrate were not significantly associated with the accuracy of reporting. These results indicate that energy intake derived from food records is an imprecise measure that substantially underestimates energy intake in middle-aged women participating in a long-term dietary-intervention trial.

Adult↗
PubMed1996

A randomized trial of the total design method for the postal follow-up of women in a cancer prevention trial.

Mail surveys have been used to follow-up early participants in a Canadian breast cancer prevention trial. To minimize non-response bias, we undertook a randomized study of two postal strategies, of which one was our usual procedure and the other was a systematic application, known as the total design method (TDM) and described by Dillman. The response rates to the two methods were 62 and 88% respectively. The TDM is a practical, cost-efficient approach to reducing non-response bias in postal surveys and as such has an important role in epidemiological research which involves healthy participants.

Adult↗
PubMed1996

Mammographic signs of potential relevance to breast cancer risk: the agreement of radiologists' classification.

We have assessed the agreement of radiologists who quantitatively estimated the extent of various mammographic features of the breast. These features are of potential relevance to the estimation of the future risk of developing breast cancer. After preparation, in which various mammographic appearances and their classification were discussed and agreed upon, two radiologists, experienced in mammography, independently estimated the extent of various types of radiological density in 120 sets of mammograms, each comprised of two mediolateral and two craniocaudal views. The results showed a high level of agreement between the two radiologists in the classification of total mammographic densities (r = 0.89). For classification of specific types of density, agreement was best for homogeneous densities (r = 0.79), more intermediate for nodular densities (r = 0.71) and worst for linear densities (r = 0.48). These results show that radiologists can, with suitable preparation, identify total breast density, a mammographic sign relevant to a woman's risk of later developing breast cancer, with a high degree of agreement.

Breast Neoplasms↗
PubMed1996

Symmetry of projection in the quantitative analysis of mammographic images.

Mammographic parenchymal patterns are among the strongest indicators of the risk of developing breast cancer. Risk evaluation through breast patterns may have an important role in studies of the aetiology of breast cancer and for monitoring changes in the breast in evaluating potential risk-modifying interventions. Typically, patterns are assessed by an experienced radiologist according to Wolfe grade, or on a coarse quantitative scale according to percent density. Parenchymal characterization methods, to overcome variability of classification by human observer, are under investigation. These include image segmentation using semi-automatic thresholding and automatic classification through textural and density measures. An important practical question relates to the extent to which information about mammographic pattern is carried by any one of the four views obtained in a typical examination. Specifically, variations of right-left breast symmetry and variations between the two standard views of each breast were tested. The mammograms of 30 premenopausal women, comprising 90 images [30 each of the right cranial-caudal (RCC), left cranial-caudal (LCC) and right medial-lateral oblique (RMLO)] were evaluated. Parameters included both subjective (radiologist classification and interactive image thresholding) and objective (fractal and skewness indices) quantitative measurements of parenchymal pattern. For the parameters tested, a high degree of correlations was observed for measurements on the RCC, LCC and RMLO views. Pearson correlation coefficients between 0.86-0.96 were found for the comparisons of quantitative parameters. The strong correlations suggest that, in the study and application of mammographic density classification, representative information is provided in a single view.

Adult↗
PubMed1996

Long-term effects of participation in a randomized trial of a low-fat, high-carbohydrate diet.

In 1982 we started a series of pilot studies to examine the feasibility of dietary intervention with a low-fat, high-carbohydrate diet in women with extensive mammographic densities. The purpose of the present paper is to examine the long-term effects of participation in these studies by assessing nutrient intake and other variables several years after active participation had stopped. Two hundred sixteen women were eligible for the follow-up study and were invited to attend and interview with a dietician. Data were collected by food frequency questionnaire from 157 subjects (73%), and blood was obtained from 115 subjects. Total energy intake was slightly lower in the intervention group. Total fat and percent energy from fat were significantly lower in the intervention group. The intake of all types of fat (saturated fat, linoleic acid, and oleic acid) and dietary cholesterol was lower in the in the intervention group; however, the polyunsaturated/saturated fat ratio did not differ between the groups. Total cholesterol and apoprotein B levels were lower in the intervention group compared to the control group. Follicle-stimulating hormone was 29% higher in postmenopausal members of the intervention group than in controls, but there was no difference in levels of estradiol. A total of 19 women enrolled in pilot studies had developed breast cancer, 5.7 times the number expected, confirming that the selection of women with extensive mammographic densities does identify a high-risk group. These data suggest that even quite short periods of intensive dietary counselling may have prolonged effects on diet, and that once subjects have adopted new dietary habits, the habits may persist even in the absence of continued counselling.

Adult↗
PubMed1995

Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study.

BACKGROUND: The radiographic appearance of the female breast varies from woman to woman depending on the relative amounts of fat and connective and epithelial tissues present. Variations in the mammographic density of breast tissue are referred to as the parenchymal pattern of the breast. Fat is radiologically translucent or clear (darker appearance), and both connective and epithelial tissues are radiologically dense (lighter appearance). Previous studies have generally supported an association between parenchymal patterns and breast cancer risk (greater risk with increasing densities), but there has been considerable heterogeneity in risk estimates reported. PURPOSE: Our objective was to determine the level of breast cancer risk associated with varying mammographic densities by quantitatively classifying breast density with conventional radiological methods and novel computer-assisted methods. METHODS: From the medical records of a cohort of 45,000 women assigned to mammography in the Canadian National Breast Cancer Screening Study (NBSS), a multicenter, randomized trial, mammograms from 354 case subjects and 354 control subjects were identified. Case subjects were selected from those women in whom histologically verified invasive breast cancer had developed 12 months or more after entering the trial. Control subjects were selected from those of similar age who, after a similar period of observation, had not developed breast cancer. The mammogram taken at the beginning of the NBSS was the image used for measurements. Mammograms were classified into six categories of density, either by radiologists or by computer-assisted measurements. All radiological classification and computer-assisted measurements were made using one craniocaudal view from the breast contralateral to the cancer site in case subjects and the corresponding breast of control subjects. All P values represent two-sided tests of statistical significance. RESULTS: For all subjects, there was a 43% increase in the relative risk (RR) between the lower and the next higher category of density, as determined by radiologists, and there was a 32% increase as determined by the computer-assisted method. For all subjects, the RR in the most extensive category relative to the least was 6.05 (95% confidence interval [CI] = 2.82-12.97) for radiologists and 4.04 (95% CI = 2.12-7.69) for computer-assisted methods. Statistically significant increases in breast cancer risk associated with increasing mammographic density were found by both radiologists and computer-assisted methods for women in the age category 40-49 years (P = .005 for radiologists and P = .003 for computer-assisted measurements) and the age category 50-59 years (P = .002 for radiologists and P = .001 for computer-assisted measurements). CONCLUSION: These results show that increases in the level of breast tissue density as assessed by mammography are associated with increases in risk for breast cancer.

Adult↗