Bilateral symmetry of breast tissue composition by magnetic resonance in young women and adults.

BACKGROUND: Some reports suggest that there is a slightly higher frequency of breast cancer in the left breast compared with the right in middle-aged women. The reasons for this association are unknown. The water and fat content of both breasts was compared using magnetic resonance (MR). Breast water by MR reflects fibro-glandular tissue and is strongly positively correlated with percent mammographic density, a strong risk factor for breast cancer. METHODS: Magnetic resonance was used to measure fat and water content of the breast in 400 young women aged 15-30 years and a random sample of 100 of their mothers. All MR examinations were carried out using a 1.5T MR system, and 45 contiguous slices were obtained in the sagittal plane. One reader identified the breast tissue in the image, and subsequently, fat and water content was calculated using a three-point Dixon technique. Left- and right-sided images were read independently in random order. RESULTS: In young women, mean percent water was on average 0.84 % higher in the right compared with the left breast (p < 0.001) and total breast water was on average 6.42 cm(3) greater on the right side (p < 0.001). In mothers, there were no significant differences in any breast measure between right and left sides. CONCLUSION: The small differences in breast tissue composition in young women are unlikely to be associated with large differences in breast cancer risk between sides. The reported excess of left-sided breast cancer in older women is unlikely to be explained by differences in breast tissue composition.

Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial.

OBJECTIVE: We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk. DESIGN: This study was a two-centre, two-armed, randomized controlled trial. The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week, with at least three of the sessions being facility based. The control group was asked not to change their activity and both groups were asked not to change their diet. SUBJECTS: A total of 320 postmenopausal, sedentary, normal weight-to-obese women aged 50-74 years who were cancer-free, nondiabetic and nonhormone replacement therapy users were included in this study. MEASUREMENTS: Anthropometric measurements of height, weight and waist and hip circumferences; dual energy X-ray absorptiometry measurements of total body fat; and computerized tomography measurements of abdominal adiposity were carried out. RESULTS: Women in the exercise group exercised a mean of 3.6 days (s.d.=1.3) per week and 178.5 min (s.d.=76.1) per week. Changes in all measures of adiposity favored exercisers relative to controls (P<0.001). The mean difference between groups was: -1.8 kg for body weight; -2.0 kg for total body fat; -14.9 cm(2) for intra-abdominal fat area; and -24.1 cm(2) for subcutaneous abdominal fat area. A linear trend of greater body fat loss with increasing volume of exercise was also observed. CONCLUSION: A 1-year aerobic exercise program consistent with current public health guidelines resulted in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer.

Mammographic density, lobular involution, and risk of breast cancer.

In this review, we propose that age-related changes in mammographic density and breast tissue involution are closely related phenomena, and consider their potential relevance to the aetiology of breast cancer. We propose that the reduction in mammographic density that occurs with increasing age, parity and menopause reflects the involution of breast tissue. We further propose that age-related changes in both mammographic density and breast tissue composition are observable and measurable phenomena that resemble Pike's theoretical construct of 'breast tissue ageing'. Extensive mammographic density and delayed breast involution are both associated with an increased risk of breast cancer and are consistent with the hypothesis of the Pike model that cumulative exposure of breast tissue to hormones and growth factors that stimulate cell division, as well as the accumulation of genetic damage in breast cells, are major determinants of breast cancer incidence.

Critical appraisal of the evidence that dietary fat intake is related to breast cancer risk in humans.

A critical appraisal was undertaken of the evidence that dietary fat intake is related to breast cancer risk by application of the criteria for causal inference proposed by Bradford Hill to the published evidence that relates dietary fat to breast cancer risk in humans. These criteria concern the consistency, strength, and temporal relationships of possible causative associations and also require the existence of a biologic gradient and examine the extent to which the proposed causal association is in keeping with other biological and epidemiological knowledge. The published reports were inconsistent in their ability to detect a significant association between dietary fat and breast cancer risk, correlation studies that examined the effect of fat over large ranges being largely positive, and studies with stronger designs (case-control, cohort) that examined fat intake over much smaller ranges being largely negative. It was postulated that methodologic limitations associated with the design of the latter studies, in particular the small ranges of fat intake examined and inaccuracies in the measurement of fat intake, may have obscured any relationships between dietary fat and breast cancer that did exist. The remaining criteria, with the exception of temporality and epidemiological coherence, were not satisfied. Insufficient evidence existed to conclude a causal association existed between dietary fat and breast cancer risk in humans. A need for further study was identified in several areas, and it was concluded that intervention studies that examined the effect of fat over large ranges were most likely to yield the information required to determine whether dietary fat intake was causally related to breast cancer risk.

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.

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.

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.

Mammographic patterns and breast cancer risk: methodologic standards and contradictory results.

The claim that classification of the pattern of the breast parenchyma upon mammography can distinguish groups at different risks for breast cancer has been examined by 17 other studies published in the English language literature with contradictory results; this controversy was assessed by us in examination of these studies for their adherence to commonly accepted methodologic standards for the investigation of causal relationships. The nine standards for the examination of the studies included a description of the way the study population had been assembled and followed up and descriptions of the methods of mammographic pattern classification and breast cancer risk analysis. A strong association was found between the standards adopted by a study and the obtained results. Among nine cohort and case-control studies that found a statistically significant association between mammographic pattern and breast cancer risk, all met at least four standards, whereas only two of six "negative" cohort or case-control studies met as many as four standards. Among prevalence surveys, the association between methods and results was less striking, but several negative prevalence surveys were associated with "positive" cohort studies employing the same group of patients. These results indicate that methodologic differences among studies contribute substantially to the controversy surrounding this subject. Studies that follow the usual scientific methods employed in the epidemiologic investigation of risk generally have confirmed an association between mammographic pattern and breast cancer risk.

Body weight and prognosis in breast cancer.

We have examined the relationship between risk factors for breast cancer incidence and the subsequent prognosis of breast cancer among patients in a randomized controlled trial of adjuvant ovarian ablation. Body weight was the only risk factor found to be associated with statistically significant differences in survival. This finding could not be explained by a disproportionate number of anatomically more advanced tumors in the heavier women. In premenopausal women aged 45 years or more, the only group to benefit from adjuvant ovarian ablation, there was an interaction of treatment and weight, suggesting that weight exerts its influence on prognosis by a hormonal mechanism. The prognostic effect of weight was generally most marked in patients with tumors whose prognostic characteristics were favorable, and in these patients weight loss as an adjuvant treatment may reduce the frequency of disease recurrence.

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.

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.

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.

Mammographic densities and risk of breast cancer among subjects with a family history of this disease.

BACKGROUND: A family history of breast cancer is known to increase risk of the disease, but other genetic and environmental factors that modify this risk are likely to exist. One of these factors is mammographic density, and we have sought evidence that it is associated with increased risk of breast cancer among women with a family history of breast cancer. METHODS: We used data from a nested case-control study based on the Canadian National Breast Screening Study (NBSS). From 354 case patients with incident breast cancer detected at least 12 months after entry into the NBSS and 354 matched control subjects, we analyzed subjects who were identified as having a family history of breast cancer according to one of three, nonmutually exclusive, criteria. We compared the mammographic densities of case patients and control subjects by radiologic and computer-assisted methods of measurement. RESULTS: After adjustment for other risk factors for breast cancer, the relative risks (RRs) between the most and least extensive categories of breast density were as follows: For at least one first-degree relative with breast cancer, RR = 11.14 (95% confidence interval [CI] = 1.54-80.39); for at least two affected first- or second-degree relatives, RR = 2.57 (95% CI = 0.23-28.22); for at least one first- or second-degree relative with breast cancer, RR = 5.43 (95% CI = 1.85-15.88). CONCLUSIONS: These results suggest that mammographic density may be strongly associated with risk of breast cancer among women with a family history of the disease. Because mammographic densities can be modified by dietary and hormonal interventions, the results suggest potential approaches to the prevention of breast cancer in women with a family history of breast cancer.

Clinical trial of low-fat, high-carbohydrate diet in subjects with mammographic dysplasia: report of early outcomes.

Despite evidence that dietary fat intake may influence breast cancer risk, there is little information about the effects of dietary fat on the human breast. We have studied the effects of dietary fat on the breast by examining the influence of dietary fat reduction on mammographic dysplasia (nodular or sheetlike areas of radiological density). Subjects with mammographic dysplasia were randomly allocated to a control group, in which they received advice about maintaining a balanced diet (36% of calories as fat), or an intervention group, in which they were taught to reduce dietary fat to a target of 15% of calories. A total of 295 patients consented to randomization, and after 1 year, 20% of the intervention group and 5% of the control group had dropped out (failed to keep appointments and provide nutrient data). The remaining patients closely adhered to the dietary goals of the study as assessed by food records, chemical analysis of duplicate meals, and serum cholesterol measurements. Comparison of mammograms before and after 1 year of dietary fat reduction shows no significant influence on the extent or density of mammographic dysplasia. Surgical biopsies performed in subjects after entry in the study showed five cancers in the control group and two cancers in the intervention group; this total of seven cancers is four times the number expected. These data show that clinical trials of the effects of dietary fat reduction on breast cancer risk are feasible and that long-term compliance with a low-fat diet can be achieved, and they confirm that the patients selected because they had mammographic dysplasia had increased risk of breast cancer.

Observer variation in the interpretation of xeromammograms.

We have examined variation in the interpretation of xeromammograms among radiologists designated to take part in a Canadian multicenter randomized controlled trial of screening for breast cancer. Radiologists read 100 xeromammograms comprising 10 histologically proved cancers, 40 benign abnormalities, and 50 normal films. Radiologists' opinions differed widely on the frequency of suspected or identified cancer. The diagnostic category "suspicion of cancer" or "cancer" was selected by radiologists for 10-55% of the films, and biopsy or aspiration was recommended for 21 to 53% of patients whose films were examined. Agreement on specific diagnostic categories was greatest for the diagnosis of cancer; agreement was least for the diagnosis of benign abnormalities and intermediate for the diagnosis of normality. Known cancers were in general correctly identified. These results indicate a need for development of methods to reduce observer variation in a interpretation of xeromammograms while preserving diagnostic sensitivity and validity. Results also emphasize the importance of developing strategies to ensure quality control in multicenter trials.

A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer.

This study was designed to assess the role of dosage of chemotherapy for treatment of metastatic breast cancer. One hundred thirty-three patients without prior chemotherapy for metastatic disease were randomly allocated to receive two different dose levels of cyclophosphamide (C), methotrexate (M), and fluorouracil (F), administered intravenously (IV) every 3 weeks. Patients were stratified by sites of disease (visceral, bone, or soft-tissue dominant) and by interval from primary surgery to first recurrence. Doses on the higher-dose arm were 600 mg/m2 (C,F) and 40 mg/m2 (M) with escalation if possible; doses on the lower-dose arm were 300 mg/m2 (C,F) and 20 mg/m2 (M) without escalation. Patients who failed to respond to lower-dose CMF were crossed over to the higher-dose arm. Patients randomized to the higher-dose arm had longer survival measured from initiation of chemotherapy (median survival, 15.6 months v 12.8 months, P = .026 by log-rank test), but the effect of dose was of borderline significance (P approximately 0.12) when adjusted for a chance imbalance between the two arms in the time from first relapse to randomization, using the Cox proportional hazards model. Response rates (International Union Against Cancer [UICC] criteria) for patients with measurable disease were higher-dose arm: 16/53 (30%) and lower-dose arm: 6/53 (11%), (P = .03). Only one of 37 patients responded on crossover from the lower- to the higher-dose arm. Patients experienced more vomiting, myelosuppression, conjunctivitis, and alopecia when receiving higher doses of chemotherapy. A series of 34 linear analogue self-assessment scales were used to make detailed quality of life assessments on a subset of 49 patients. These scales confirmed greater toxicity in the immediate posttreatment period, but also a trend to improvement in general health and some disease-related indices, in patients receiving higher-dose chemotherapy. This trial suggests that better palliation is achieved by using full-dose chemotherapy.

Pretherapeutic morbidity in the prognostic staging of acute leukemia.

To classify the clinical severity of acute leukemia, we have used the degrees of pretherapeutic infection and hemorrhage to construct a taxonomy containing three "stages". The stages are associated with survival gradients that are clinically and statistically distinctive in both acute lymphoblastic leukemia and acute nonlymphoblastic leukemia. Median survival ranged from 64.0 months for stage 1 to 10.5 months for stage 3 in acute lymphoblastic leukemia, and from 7.1 months for stage 1 to 1.2 months for stage 3 in acute nonlymphoblastic leukemia. The gradients, which persist when other prognostic factors and secular therapeutic changes are taken into account, are more distinctive than those found with other forms of stratification.

The frequency of malignant neoplasms in patients with polymyositis-dermatomyositis. A controlled study.

Seventy-one patients with polymyositis-dermatomyositis (PM/DM) admitted to the Wellesley Hospital Rheumatic Disease Unit (RDU) in Toronto between 1965 and 1980 were followed up to 1981. The frequencies of malignant neoplasms occurring prior to or concurrent with initial RDU admission were compared, using case-control methods, with age- and sex-matched control groups with a diagnosis of any non-PM/DM rheumatic disease (rheumatic disease controls) or osteoarthritis, fibrositis, or fracture (noninflammatory musculoskeletal controls). In a cohort analysis, the incidence of malignant neoplasm subsequent to initial RDU admission in patients with PM/DM was compared with the expected incidence in the Canadian population. Fifteen of 71 patients with PM/DM had an antecedent or concurrent cancer compared with four of 71 rheumatic disease controls and one of 71 noninflammatory musculoskeletal controls. Cohort analysis showed no increase in the number of subsequent malignant neoplasms in patients with PM/DM compared with the age- and sex-matched Canadian population.

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.

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.