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Biomedical subjects

N F Boyd

Publications and source records attributed to N F Boyd.

At least 19 recordsLinked to original sources
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↗
PubMed1992

The risk of breast cancer associated with mammographic parenchymal patterns: a meta-analysis of the published literature to examine the effect of method of classification.

The appearance of the breast parenchyma as seen on mammography is known to vary between individuals. The evidence is reviewed that some of the sources of this variation, namely, the densities referred to as "dysplasia", are related to breast cancer risk. We have carried out a meta-analysis of the published literature to determine the magnitude of the risk of breast cancer associated with mammographic densities by calculating summary odds ratios for studies grouped according to their design and the method used to classify mammographic parenchymal patterns. This has shown that subjects with mammographic densities have an increased risk of breast cancer relative to those without densities. Of the studies that used Wolfe's method of classification, cohort studies (n = 8) had a summary odds ratio of 5.19 (95% CI, 3.6 to 7.48); case control studies (n = 13) had a summary odds ratio of 1.8 (95% CI, 1.5 to 2.13); and prevalence surveys had a summary odds ratio of 0.54 (95% CI, 0.4 to 0.7). Other methods of classification, using quantitative estimates of the proportion of the breast occupied by densities, gave substantially higher odds ratios than Wolfe's system. The ability to recognize individuals within the population at different risks for breast cancer could be exploited in studies of potential etiological factors.

Breast↗
PubMed1991

The possible role of lipid peroxidation in breast cancer risk.

Breast cancer remains the commonest cause of death from cancer in women in most of the Western world. There is considerable evidence that breast cancer risk is influenced by environmental factors and can therefore potentially be modified. In this paper we describe evidence suggesting a relationship of lipid peroxidation to breast cancer risk, and propose that the method used to generate this information might usefully be applied to other disease states, and make some suggestions for further work. We have compared the urinary excretion of the mutagen malonaldehyde (MDA) in premenopausal women at different risks for breast cancer as determined by the appearance of the breast parenchyma on mammography. MDA was measured in 24-h urine samples from both groups and excretion in 30 women with mammographic dysplasia (high risk) was found to be approximately double that of 16 women without these radiological changes (p less than 0.02). These results suggest that mammographic dysplasia may be associated with lipid peroxidation. Further study of environmental factors associated with states that precede the development of breast and other cancers may lead to the identification of factors that can be modified and that may prevent the development of malignant disease.

Adult↗
PubMed1990

Evidence of lipid peroxidation in premenopausal women with mammographic dysplasia.

We have compared the urinary excretion of the mutagen malonaldehyde in premenopausal women at different risks for breast cancer as determined by the appearance of the breast parenchyma on mammography. Thirty women with extensive mammographic densities were compared with 16 controls without these radiological changes. Malonaldehyde was measured in 24-h urine samples from both groups and excretion in 30 women with mammographic dysplasia (high risk) was found to be approximately double that of 16 women without these radiological changes (P less than 0.02). These results suggest that mammographic dysplasia may be associated with lipid peroxidation and raise the possibility that mutagenic products generated by this process may influence breast cancer risk.

Adult↗
PubMed1990

Evidence of association between plasma high-density lipoprotein cholesterol and risk factors for breast cancer.

Females in western societies have higher plasma levels of high-density lipoprotein cholesterol (HDL-C) than males. The difference in plasma lipids between the sexes is believed to contribute to differences in risk of heart disease. The evidence reviewed here demonstrates that plasma levels of HDL-C are also associated with factors influencing risk of breast cancer, a leading cause of death in women in western societies. Both breast cancer risk and HDL-C levels are higher in women who live in northern European countries than in those who live in Asia, in women who have never been pregnant compared with those who have, and in women of higher socioeconomic status. HDL-C levels are also affected by several other known or suspected factors in breast cancer risk; these include dietary fat intake, alcohol consumption, endogenous hormones, and premenopausal leanness. Increases in any of these factors are known to increase the level of HDL-C. Preliminary work has also shown HDL-C levels to be higher in subjects with mammographic dysplasia and a family history of breast cancer. Further, in serum-free culture systems, HDL-C appears to possess biologic properties that may be relevant to carcinogenesis. In other areas, evidence of a relationship between increased HDL-C levels and increased breast cancer risk is either incomplete or contradictory. These areas include obesity (in the risk of postmenopausal breast cancer), use of exogenous hormones (oral contraceptives or postmenopausal estrogens), and physical exercise. In addition, both elevated and depressed levels of HDL-C have been reported in women with breast cancer. Our findings suggest an association between high HDL-C levels and the epidemiology of breast cancer risk. We recommend additional studies of plasma lipid level as a possible risk factor for this disease.

Age Factors↗
PubMed1990

Body size and breast cancer prognosis: a critical review of the evidence.

There is currently controversy about the effect of body size on the prognosis of patients with breast cancer. In order to clarify the prognostic importance of body size, and to determine whether the effect varies across subgroups of patients, a critical appraisal of the published literature was undertaken. Thirteen cohort studies and one case-control study were identified that examined the prognostic effect of body size. Methodologic standards were developed that reflected those features of study design considered most important in studies of prognosis in breast cancer, and were independently applied to each report by each of the authors. When the effects of methodologic differences among the studies were controlled, a modest prognostic effect of body size was identified. This effect appeared to be greatest in postmenopausal women, in those with little or no involvement of axillary nodes, and to be independent of other prognostic factors. Additional investigation is recommended to determine the prognostic effects of body size in postmenopausal women with axillary node negative breast cancer and in women receiving systemic adjuvant therapy, and to determine the pathophysiological basis for these effects. Intervention studies to determine the effects of altering body size may also be indicated.

Body Constitution↗
PubMed1990

Ratings of the importance of quality of life variables: therapeutic implications for patients with metastatic breast cancer.

Metastatic breast cancer cannot be cured with currently available therapeutic agents, and the objectives of treatment must, therefore, be directed towards other goals that include the relief of symptoms and the preservation or restoration of function. The main objective of the study reported here was to examine the relative importance of 28 items concerned with general health or with disease and treatment to a group of patients with metastatic breast cancer. All items concerned aspects of quality of life whose relevance and importance to patients with metastatic breast cancer had been shown in previous work. Patients rated items according to importance using two methods, a Q sort and a linear analogue rating. General health items, notably self-care, mobility, and physical activity, appetite, sleep, and family relationships were ranked in the upper quartile of the group of items rated. By contrast, items concerned directly with the common side-effects of chemotherapy were given lower rankings. The ratings were shown to be reproducible. These results emphasize the importance of including in clinical trials of therapy that are palliative in intent, endpoints that include those aspects of quality of life that are of greatest importance to patients.

Adult↗
PubMed1990

Quantitative changes in dietary fat intake and serum cholesterol in women: results from a randomized, controlled trial.

We compared observed and predicted changes in serum cholesterol in women with mammographic dysplasia who participated for 12 mo in a randomized, controlled trial of a low-fat, high-carbohydrate diet, in which total fat intake was reduced from an average of 37% of calories to 21% and carbohydrate intake increased from 44% to 52% of calories. Changes observed in serum cholesterol were greater than those predicted (by the formulas of Hegsted and Keys) for subjects with initial serum cholesterol values in the upper tertile of the population, were not significantly different from those predicted for subjects with baseline values in the middle tertile, and were significantly less than those predicted for subjects with initial values in the lower tertile. These results show that the usefulness of serum cholesterol as a marker of change in dietary fat intake in women depends on the distribution of serum cholesterol values in the population studied.

Adult↗
PubMed1989

Cyclical mastopathy: an evaluation of methods of assessment.

We have evaluated three methods of assessing patients with cyclical breast symptoms (cyclical mastopathy--CM). One method, a screening questionnaire, was used to identify women with CM, and two others, a symptom severity questionnaire and a daily diary, were used prospectively to record the severity of symptoms in relation to the menstrual cycle. The screening questionnaire was assessed for test-retest reliability and for agreement between the recalled severity of symptoms and those recorded during prospective measurement. The symptom severity questionnaire and diary were assessed by examining their ability to discriminate between pre- and postmenstrual phases of the menstrual cycle, differences in symptom severity at these times being the cardinal feature of CM. Test-retest reliability of premenstrual symptoms by the screening questionnaire gave correlation coefficients over 0.70 for 9 of the 11 items assessed. The symptom severity questionnaire showed significant differences between pre- and post-menstrual scores for 8 of the 11 items assessed and the diary for each of the 2 items assessed. Comparison of symptom severity as recalled and as prospectively recorded showed only modest agreement. These results show that the instruments used to assess symptom severity performed satisfactorily but that the screening questionnaire used to identify women with CM, although reliable, correlated only moderately well with prospective measurement.

Adolescent↗
PubMed1989

A review of the methods used by studies of dietary measurement.

Studying the association between diet and disease requires reliable and valid methods for the assessment of diet. The authors reviewed the literature concerned with the assessment of these aspects of the measurement of dietary intake. Studies were examined for the stated purpose and scope of the dietary instrument, for a description of the instrument itself, for any methods employed to train individuals in its use and for the methods used to assess its reliability and validity. Of the 59 studies reviewed, 54% described fully the dietary method used. Of the 39 studies that described the results using questionnaires, 51% gave specific information on questions asked and only 18% included the questionnaire itself. Reliability was assessed in 26 studies and 74% (19) used the test-retest reliability and 22% (6) used proxies to assess reliability. Validity was assessed in 46 studies and 83% (38) used indirect methods that compared the results of one dietary method (e.g. 24 hr recall) with another more extensive one (e.g. diet history). Thirty five percent (16) used biochemical and 15% (7) used other methods. This review suggests several directions that might be usefully followed in conducting and reporting further research in the development of methods to assess diet.

Diet Surveys↗
PubMed1989

Plasma lipids in premenopausal women with mammographic dysplasia.

Epidemiological evidence indicates that mammographic dysplasia is associated with an increased risk of breast cancer, particularly in premenopausal women. To examine biochemical associations with mammographic dysplasia we have compared premenopausal women with different patterns of the breast parenchyma on mammography. One group had extensive radiological dysplasia (n = 30) and the other no dysplasia (n = 16). Both groups were recruited from mammographic units in the same way and then compared according to epidemiological risk factors, anthropometric measures, nutrient intake and plasma levels of oestradiol, progesterone and prolactin obtained in both follicular and luteal phases of the menstrual cycle as well as total plasma cholesterol and lipid fractions. Women with mammographic dysplasia were found to be leaner, more often nulliparous and to consume more alcohol than women without these radiological changes. Mammographic dysplasia and a family history of breast cancer were found to be independently associated with significantly higher levels of high density lipoprotein cholesterol (HDL-C) after taking into account the possible confounding effects of percentage body fat, parity and consumption of alcohol and dietary fat. Triglyceride levels were also independently associated with a family history of breast cancer. We conclude that further investigation is warranted of the role of plasma lipids in relation to breast cancer risk.

Adult↗