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Biomedical subjects

N F Boyd

Publications and source records attributed to N F Boyd.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cyclical mastopathy and premenopausal breast cancer risk. Results of a case-control study.

Cyclical mastopathy (CM) is a common clinical syndrome of premenstrual breast swelling and tenderness. Its symptoms are relieved by reduction in dietary fat intake and, because fat intake may be associated with breast cancer risk, it was hypothesized that CM may also be related to breast cancer risk. This case-control study included 192 premenopausal women with a recent history of axillary node-negative breast cancer and 192 age-matched premenopausal controls. Subjects provided information on diet and risk factors, and they recorded breast symptoms prospectively during one menstrual cycle. Symptoms in the noncancerous breast of cases and the matched (right or left) breast of controls were examined. A cyclical pattern of symptoms was identified in both groups; breast tenderness scores were similar postmenstrually (p = 0.31) but were significantly higher premenstrually in the case group (p = 0.03). Cases also had a greater premenstrual increase in breast tenderness than controls (p = 0.03). When the effects of other risk factors for breast cancer were included in multivariate analyses, the association of cyclical tenderness with breast cancer persisted (p = 0.05), the odds ratio for severe tenderness being 3.32. Thus, we have identified an association of cyclical breast tenderness with breast cancer risk in premenopausal women. The association persists after consideration of diet and the effects of other breast cancer risk factors.

Adult↗
PubMed1995

Mammographic densities as a criterion for entry to a clinical trial of breast cancer prevention.

The most convincing evidence that a factor such as dietary fat is causally related to breast cancer would be obtained from a randomised controlled trial in which exposure to dietary fat intake was systematically varied. A limitation of randomised controlled trials of breast cancer prevention, however, is the large sample size required to detect plausible reductions in risk resulting from the intervention. We describe here experience over a period of 9 years with the use of one risk factor for breast cancer as a criterion for entry to a clinical trial of breast cancer prevention. The risk factor used was the presence of extensive densities in the breast tissue on mammography, which has been found by several investigators to be strongly associated with risk of breast cancer. Using this criterion for selection, 1800 subjects of mean age 46 years were enrolled between 1982 and 1986, and again between 1988 and the present. Throughout this period, the point estimate of annual invasive cancer incidence was approximately 6 per 1000 per year. The observed cancer incidence has been consistently 4-5 times the incidence expected from age-specific breast cancer incidence data for women living in Ontario. These data show that the selection of subjects for a clinical trial of breast cancer prevention using the criterion of extensive breast parenchymal densities does identify a group at substantially increased risk of breast cancer. Use of this criterion for the selection of subjects can substantially reduce the sample size required for a clinical trial of a preventive strategy.

Adult↗
PubMed1995

Quantitative evaluation of mammographic densities: a comparison of methods of assessment.

Differences in the proportion of the breast occupied by mammographic densities have been shown to be associated with differences in breast cancer risk. However, estimation of these densities by radiologists may be subject to error, and it is likely that quantitative measurement will reduce misclassification of densities and strengthen their association with risk of breast cancer. The objective of this study was to compare the extent of mammographic densities estimated subjectively by an experienced radiologist with the measured extent of densities using a digital planimeter. A total of 225 sets of mammograms from women aged 40-49 years and enrolled in the Canadian National Breast Screening Study (NBSS) were selected. The extent of the radiological densities was estimated visually by one radiologist. Independently, the total area of the breast and the areas of density were traced and measured using a digital planimeter. Visual estimations and measurements of mammographic densities were then compared to determine the extent of agreement between the two methods. In general, the two methods showed good agreement (kappa = 0.78). The measured area of mammographic densities tended to be slightly greater than the radiologist's estimations. Both methods were highly reproducible (radiologist-dependent method, kappa = 0.89; quantitative method, r = 0.95, P = 0.0001). Our results indicate that measurement of the area of mammographic density using a quantitative method is reliable, and correlates well with assessment by an experienced radiologist. The method may be useful for identifying women at increased risk of breast cancer.

Absorptiometry, Photon↗
PubMed1995

Parenchymal patterns of the breast defined by real time ultrasound.

The association of mammographic parenchymal patterns of the breast with breast cancer risk has been studied extensively but there is little information about the distribution of different patterns in populations at different risks for breast cancer. Such information could be obtained if a risk-free method of breast examination were available that could be applied to the general population. We have evaluated real time ultrasound for this application by comparing the parenchymal pattern as assessed by mammography with the extent of echogenicity in the breast on ultrasound examination in 102 subjects. Subjects were examined by both methods, the mammographic and ultrasound images independently classified, and the proportion of the breast occupied by radiological density or ductal prominence compared with the extent of echogenic areas on ultrasound. These two methods of classifying mammographic parenchymal patterns were found to be strongly correlated. Real time ultrasound may therefore be useful in the epidemiological study of mammographic pattern and breast cancer risk.

Breast↗
PubMed1995

Plasma lipids, lipoproteins, and familial breast cancer.

We have examined the relationship between plasma lipids, lipoproteins, and a family history of breast cancer. We measured the plasma lipids and lipoproteins in unaffected female members of the nuclear family of women with familial breast cancer and compared them with those of the female members of the nuclear family of women with sporadic breast cancer. A mean number of 3.3 relatives of mean age 35 years were studied in 23 pairs of familial and sporadic breast cancer families. After adjustment in multivariate analysis for variables that either differed between high and low risk families, or were significantly associated with plasma levels or lipoproteins, statistically significant differences were found in plasma levels of total cholesterol, low density lipoprotein cholesterol, and apoprotein B, all of which were lower in familial breast cancer than in sporadic breast cancer families. These data suggest that inherited factors associated with breast cancer risk may play a role in determining plasma lipid and lipoprotein levels and that lipid regulatory genes should be considered in this context.

Adult↗
PubMed1994

The quantitative analysis of mammographic densities.

Quantitative classification of mammographic parenchyma based on radiological assessment has been shown to provide one of the strongest estimates of the risk of developing breast cancer. Existing classification schemes, however, are limited by coarse category scales. In addition, subjectivity can lead to sizeable interobserver and intraobserver variations. Here, we propose an interactive thresholding technique applied to digitized film-screen mammograms, which assesses the proportion of the mammographic image representing radiographically dense tissue. Observers viewed images on a CRT display and selected grey-level thresholds from which the breast and regions of dense tissue in the breast were identified. The proportion of radiographic density was then calculated from the image histogram. The technique was evaluated for the mammograms of 30 women and is well correlated (R > 0.91, Spearman coefficient) with a six-category subjective classification of radiographic density by radiologists. The technique was found to be very reliable with an intraclass correlation coefficient between observers typically R > 0.9. This technique may have a role in routine mammographic analysis for the purpose of assessing risk categories and as a tool in studies of the etiology of breast cancer, in particular for monitoring changes in breast parenchyma during potential preventive interventions.

Absorptiometry, Photon↗
PubMed1993

A study of diet and breast cancer prevention in Canada: why healthy women participate in controlled trials.

Little research has been undertaken to determine why healthy people agree to enroll in randomized controlled trials of cancer prevention. This study describes the beliefs of Canadian women participating in a trial designed to determine the effect of reducing dietary fat on the development of breast cancer. Healthier eating, nutritional counseling, contributing to science, and helping others were the most frequently cited advantages of participation. Weight control and general better health were specifically associated with the dietary regimens. Attending appointments and difficulties when eating out were the main disadvantages of participation. Suggestions that would promote adherence to the trial protocol also were elicited. Responses cited most often included opportunities to meet other participants, more nutritional counseling (particularly psychological tips), updates about the trial, and more recipes. Attention should be paid to these suggestions as they characterize some of the major determinants of adherence behavior.

Adult↗
PubMed1993

A meta-analysis of studies of dietary fat and breast cancer risk.

There is strong evidence that breast cancer risk is influenced by environmental factors, and animal experiments and human ecological data suggest that increased dietary fat intake increases the incidence of the disease. Epidemiological evidence on the relationship of dietary fat to breast cancer from cohort and case control studies has however been inconsistent. To examine the available evidence we have carried out a meta-analysis to summarise quantitatively the large published literature on dietary fat in the aetiology of breast cancer. After assembling all of the published case control and cohort studies, we extracted the relative risk in each study that compared the highest to the lowest level of intake. We then calculated a summary relative risk for all studies. The summary relative risk for the 23 studies that examined fat as a nutrient was 1.12 (95% CI 1.04-1.21). Cohort studies had a summary relative risk of 1.01 (95% CI 0.90-1.13) and case control studies a relative risk of 1.21 (95% CI 1.10-1.34). Summary estimates of risk for specific types of fat excluded unity for only saturated fat. For the 19 studies that examined food intake, the summary relative risks were 1.18 (95% CI 1.06-1.32) for meat, 1.17 (95% CI 1.04-1.31) for milk, and 1.17 (95% CI 1.02-1.36) for cheese. Summary relative risks for total fat intake were examined for several potential modifying factors. Regression analysis showed that European studies were more likely than studies done in other countries to show an increased relative risk associated with dietary fat and breast cancer, after taking into account potential modifying factors that included study design and quality.

Animals↗
PubMed1993

Mammographic parenchymal patterns: a marker of breast cancer risk.

There is now a large amount of evidence showing that mammographic densities are an indicator of increased risk of breast cancer. There is as yet no generally agreed upon and recognized method of classifying these densities, although the available evidence shows that quantitative description of densities creates larger gradients of risk than Wolfe's classification and larger risk gradients than most other risk factors for breast cancer. It seems likely that improved methods of describing densities quantitatively, and possibly other methods of characterizing the tissue changes that are responsible for the densities, will allow greater discrimination. However, it is already clear that breast cancer develops in a large number of women who do not have radiologic changes indicating increased risk, and that it is unlikely that mammographic pattern, or any other risk factor for breast cancer identified to date, will be useful for the selection of women for mammographic screening. Although mammographic densities are associated with an increased risk of developing histologic changes that are risk factors for breast cancer, the histologic feature most consistently associated with mammographic densities is stromal fibrosis. We suggest that the relation between stromal fibrosis and risk of breast cancer can be explained by the known actions of a variety of growth factors that are thought to play a role in a number of aspects of breast development and carcinogenesis. The association between mammographic densities and several other risk factors for breast cancer suggests that these factors may also modulate the activity of growth factors in breast tissue, and that this may be the means by which they influence breast cancer risk. Further research is needed to determine whether differences in the activity of growth factors in breast tissue can be found in association with radiologic and other risk factors for breast cancer. The available evidence indicates, therefore, that mammographic parenchymal patterns do, at least in part, meet the criteria outlined in the introduction of this paper. Some mammographic appearances are associated with a substantial increase in the risk of breast cancer, and, as shown by observations on the effects of hormone use, are capable of change. Mammographic densities have also been found to be associated with biochemical characteristics of possible relevance to carcinogenesis. The appearances that are related to risk may, therefore, be most useful as a means of investigating the etiology of breast cancer and of testing hypotheses about potential preventive strategies.

Adult↗
PubMed1992

Relationship between mammographic and histological risk factors for breast cancer.

BACKGROUND: Information on breast cancer risk can be obtained both from the histological appearance of the breast epithelium in biopsy specimens and from the pattern of parenchymal densities in the breast revealed by mammography. It is not understood, however, how parenchymal densities influence breast cancer risk or whether these densities are associated with histological risk factors. PURPOSE: We have estimated, in a large cohort of women, the relative risk of detecting carcinoma in situ, atypical hyperplasia, hyperplasia without atypia, or nonproliferative disease in biopsy specimens from women with different extents of mammographic density. We also examined the association between these histological classifications and radiological features present specifically at the biopsy site. METHODS: The source of study material was a population of women aged 40-49 years who were enrolled in the Canadian National Breast Screening Study (NBSS). Mammograms from women who had undergone a biopsy (n = 441) and from a comparison group of women (n = 501) randomly selected from the mammography arm of the NBSS were classified according to the extent of mammographic density. The corresponding histological slides were independently classified by a review pathologist. RESULTS: Compared with women showing no mammographic densities, women with the most extensive densities (i.e., occupying greater than 75% of the breast volume) had a 9.7 times greater risk of developing carcinoma in situ or atypical hyperplasia (95% confidence interval [CI] = 1.75-53.97), a 12.2 times greater risk of developing hyperplasia without atypia (95% CI = 2.97-50.14), and a 3.1 times greater risk of developing non-proliferative disease (95% CI = 1.20-8.11). The gradients in risk were not monotonic across the five classifications of mammographic density. The association could not be explained by the presence of mammographic densities at the biopsy site, but calcification at the biopsy site was strongly associated with high-risk histological changes (relative risk = 24; 95% CI = 5.0-156.0). CONCLUSIONS: These results suggest that the radiological patterns referred to as mammographic dysplasia may influence breast cancer risk by virtue of their association with high-risk histological changes in the breast epithelium. IMPLICATIONS: Identification of the factors responsible for high-risk histological changes may offer new insights into the etiology of breast cancer and potentially lead to the development of methods for its prevention.

Adult↗
PubMed1992

Quantitative magnetic resonance imaging parameters and their relationship to mammographic pattern.

BACKGROUND: Breast cancer exhibits wide international variation in incidence, which has led to the identification of several factors correlating with the risk of the disease. Magnetic resonance imaging (MRI) techniques can provide quantitative information about the biological and physical properties of tissue. PURPOSE: This work tested several magnetic resonance tissue parameters for their ability to distinguish quantitatively between breast tissues in subjects at substantially different risk for breast cancer as defined indirectly by their parenchymal pattern on mammograms. METHODS: Quantitative MRI parameters (relative water content, longitudinal relaxation time [T1], and transverse relaxation time [T2]) were measured for breast tissue using newly developed techniques in two groups of women with mammographic parenchymal appearance associated with high (Dy pattern [i.e., extensive nodular or diffuse density]; n = 12) or low (N1 pattern [i.e., breast containing mainly fat]; n = 11) risk of breast cancer. RESULTS: The two groups have significantly different average relative water content (P less than .0001) and average T1 (P less than .0001). Pixel histograms of T2 values show marked differences between the two groups which can be characterized with a fourth moment parameter. CONCLUSIONS: Quantitative MRI techniques exhibit good potential for assessing tissue characteristics in the breast that are associated with risk of breast cancer. IMPLICATIONS: Future work will address the direct correlation of MRI parameters with risk of breast cancer.

Adult↗
PubMed1992

Case-control study of factors associated with failure to detect breast cancer by mammography.

BACKGROUND: Although mammography is widely used to detect breast cancer, it is recognized that not all cancers can be seen on mammographic images. PURPOSE: Our purpose was to examine factors associated with failure to detect breast cancer by mammography. METHODS: A case-control study was carried out in which subjects in whom histologically verified breast cancer was not detected by mammography (false negatives) were contrasted with subjects in whom breast cancer had been detected by mammography (true positives). Mammograms from individuals with histologically confirmed breast cancer were classified independently by two radiologists who were unaware of the clinical or other characteristics of the subjects. Histologic slides of all tumors were reviewed by one pathologist. RESULTS: Three variables were found to be independently and significantly associated with failure to detect breast cancer by mammography. Breast cancer was less likely to be detected by mammography in the presence of extensive parenchymal densities (odds ratio [OR] = 9; 95% confidence interval [CI] = 1.8-44.3), a tumor of lobular histology (OR = 7; 95% CI = 2.2-22.1), and tumors of small size (OR = 0.10; 95% CI = 0.0-0.9). CONCLUSION: Our results indicate that biologic factors are associated with failure to detect some breast cancers by mammography and indicate directions for future research in breast imaging.

Adult↗
PubMed1992

Atypical hyperplasia and breast cancer risk: a critique.

The purpose of this paper is to examine critically the evidence that atypical hyperplasia (AH) is a risk factor for breast cancer. First, we appraised studies that have examined the association between AH and breast cancer risk for their adherence to widely accepted standards for the conduct of research. Second, we examined the available evidence to determine the plausibility of an association between AH and breast cancer risk using the guidelines proposed by Bradford Hill. A total of 18 studies (11 cohort studies, two case-control studies, and five cross-sectional studies) were found that were published in the English language from January 1960 to March 1992 that examined the association of AH as a distinct entity and breast cancer risk. A systematic approach was adopted to examine the collected studies for their adherence to methodologic standards, which showed wide variation among studies. A meta-analysis was carried out, based on a total sample size of 182,980 women. Of 16 studies that gave point estimates of risk, 14 exceeded unity and 12 were significantly different from unity. The pooled estimate from all studies of the association between AH and breast cancer, gave an overall odds ratio (OR) of 3.67 (95 percent confidence interval = 3.16-4.26). The test of the hypothesis of homogeneous association was rejected (chi 2 = 151.6, df = 14, P < 0.0001), indicating significant variability among the ORs of individual studies. The conclusions from the application of the Bradford Hill criteria indicated strongly that AH is a risk factor for breast cancer.

Bias↗
PubMed1992

Dietary fat and breast cancer risk: the feasibility of a clinical trial of breast cancer prevention.

Animal experimental evidence and human ecological data suggest that dietary fat intake is related to breast cancer risk. Epidemiological studies within countries have given inconsistent results but are limited by the restricted range of dietary intake found in Western populations and by error in the measurement of fat consumption. Experimental evidence, derived from controlled clinical trials in which the range of fat intake is increased beyond that seen in most Western populations, is capable of overcoming this limitation of observational epidemiology, and would provide the strongest evidence available concerning the relationship of dietary fat intake to breast cancer risk. Further, such trials are the only means likely to answer the question of whether breast cancer risk in high-risk subjects can be modified by changing dietary fat intake. We describe here several aspects of the feasibility of an experimental approach to this problem, including the identification of subjects at increased risk for breast cancer, and the demonstration that such subjects will enter a clinical trial of dietary fat reduction and comply with a low-fat diet. It is shown that subjects can be recruited and retained in such trials, that satisfactory dietary compliance can be achieved over at least 24 mon and that the subjects selected are at demonstrably increased risk of breast cancer. This finding indicates that it is feasible to test the dietary fat-breast cancer hypothesis experimentally by means of a clinical trial.

Adult↗
PubMed1992

A randomized controlled trial of dietary fat reduction: the retention of subjects and characteristics of drop outs.

We have examined the feasibility of carrying out a randomized controlled trial of dietary fat reduction in women at increased risk for breast cancer. The randomization was either to a control group who were taught the principles of balanced nutrition, but were not counselled to change their fat intake, or to an intervention group who were taught to reduce their dietary fat intake to 15% of total calories from a baseline average of 35% of calories. Potentially eligible subjects were women attending a breast diagnostic clinic who had the mammographic pattern of dysplasia. Subjects were recruited by letter from their referring surgeon followed by a telephone call. Subjects interested in participating in the study then entered by one of two phases. In Phase I, the study was explained, informed consent sought and willing subjects randomized to the intervention or control group. Using this procedure 227 subjects were randomized and 48 (21%) dropped out of the study in the 12 months following randomization. (A drop out was defined as a subject who persistently failed to keep appointments and provide nutrient data.) Of these drop outs, 30 (63%) occurred at or soon after randomization. A modified procedure of entry was then adopted in which subjects interested in the study were first taught the procedures involved, including keeping food records and clinic appointments, and were then asked to provide consent and randomized. Two hundred and eighty subjects were enrolled using this modified procedure and 25 (9%) have dropped out in the 12 months following randomization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗