ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics.
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The relation between benign breast disease and breast cancer was investigated in a case-control study of postmenopausal patients selected either by diagnostic procedure sampling (mammography 150 cases and controls, breast biopsy 107 cases and controls) or by conventional sampling procedures (257 controls to match total number of cases). For mammography patients, the odds ratio for association between benign breast disease and breast cancer was 0.9; for biopsy patients the odds ratio was 0.8; but by use of conventional methods, the odds ratio was elevated to a "causal" and statistically significant 2.6. When patients were classified according to cancer stage, benign breast disease was present in 56/147 patients with localised cancer compared with 24/107 patients with non-localised cancer (odds ratio 2.3). Evidence that benign breast disease is a risk factor for breast cancer may therefore be misleading if choice of control groups makes no provision for bias produced by inequalities in detection of disease.
After almost a century of research the relationship of benign breast disease to breast cancer risk is still controversial. The present investigation assessed this controversy by examining all published cohort studies that examined the risk of breast cancer in subjects with benign breast disease for their compliance with widely accepted standards for the conduct of etiologic research. Most of these studies describe the breast cancer incidence in women who have had breast biopsies. The 16 standards included a description of the population studied, a definition of benign breast disease, an account of follow-up, and a description of the analysis of risk. Of the 36 studies examined, 22 reported finding an increase in breast cancer risk in women with benign breast disease and all met more methodologic standards than the 11 studies reporting no increase in risk (3 studies reported no conclusions). In particular, none of the 11 "negative" studies calculated the number of cancers expected in the population studied, whereas all 22 "positive" studies did so. There is thus considerable statistical support from well-conducted studies for the view that benign breast disease is associated with an increase in breast cancer risk. By contrast, there is no credible support for the contrary view, which is often based on small studies in which no cancers were observed or on studies whose conclusions are not supported by an appropriate analysis of the data they contain.
Evidence from clinical follow-up studies has indicated that there is a relationship between the presence of histologically proven benign breast disease and breast cancer risk and that the level of risk varies according to the histologic category of benign breast disease. In particular, proliferative lesions without atypia are associated with a 1.5- to 2-fold increase in risk, whereas atypical hyperplasias are associated with a fourfold to fivefold increase in breast cancer risk. A number of clinical factors appear to modify the risk associated with these lesions, including the time since biopsy, menopausal status, and family history of breast cancer. Recent studies have begun to evaluate the potential role of biologic, molecular, and genetic markers in assessing breast cancer risk in patients with benign breast disease. Additional information derived from clinicopathologic follow-up studies, epidemiologic studies, and molecular and genetic studies will provide new insights into benign breast disease and breast cancer risk.
Breast diseases are a common aspect of primary care practice. Common benign and malignant breast diseases are reviewed. The evaluation of common breast problems is presented and current recommendations for diagnostic and screening mammography are discussed.
BACKGROUND: Having either a history of benign breast disease, particularly atypical hyperplasia or extensive mammographic breast density, is associated with increased breast cancer risk. Previous studies have described an association between benign breast disease histology and breast density. However, whether these features measure the same risk, or are independent risk factors, has not been addressed. METHODS: This case-control study, nested within the prospective follow-up of the Breast Cancer Detection Demonstration Project, evaluated both benign histologic and mammographic density information from 347 women who later developed breast cancer and 410 age- and race-matched controls without breast cancer. Multivariate logistic regression analyses provided maximum-likelihood estimates of the odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relative risk of breast cancer associated with each exposure. RESULTS: Adjusting for mammographic density, the OR for atypical hyperplasia was 2.1 (95% CI: 1.3-3.6), and adjusting for benign breast histology, the OR for > or = 75% density was 3.8 (95% CI: 2.0-7.2). Women with nonproliferative benign breast disease and > or = 75% density had an OR of 5.8 (95% CI: 1.8-18.6), and women with < 50% density and atypical hyperplasia had an OR of 4.1 (95% CI: 2.1-8.0). CONCLUSIONS: In this study, both benign breast disease histology and the percentage of the breast area with mammographic density were associated with breast cancer risk. However, women with both proliferative benign breast disease and > or = 75% density were not at as high a risk of breast cancer due to the combination of effects (p = 0.002) as women with only one of these factors.
BACKGROUND: Studies in animals and geographic correlations across populations suggest that fatty acid intake may have a positive relationship with breast cancer risk, but analytic epidemiologic studies of fat intake have been less supportive. Adipose tissue analysis provides a more objective assessment of intakes of fatty acids that are not endogenously synthesized than do the questionnaire survey methods used in many epidemiologic studies. PURPOSE: This case-control study of postmenopausal women was designed to examine the relationship between fatty acid composition of subcutaneous adipose tissue and risk of breast cancer and proliferative benign breast disease. In addition, we examined specific hypotheses that breast cancer risk is negatively associated with long-chain N-3 fatty acid intake, positively associated with trans fatty acid intake, and positively associated with increased intake of polyunsaturated fat together with low intake of antioxidants. METHODS: Aspirates of subcutaneous fat from the buttocks were obtained from 380 women with newly diagnosed stage I or II breast cancer and 176 with proliferative benign breast disease. A total of 397 women who were evaluated for breast abnormalities at the same institutions but did not require breast biopsy or whose biopsy revealed nonproliferative benign breast disease served as the control group. We examined associations between saturated, monounsaturated, polyunsaturated, trans, or long-chain N-3 fatty acids and breast cancer, atypical hyperplasia, or proliferative benign breast disease without atypia. RESULTS: We observed no consistent patterns of association between breast cancer risk and any of the categories of fatty acids or the individual constituent fatty acids in the adipose tissue. Saturated fatty acids were inversely associated with risk of proliferative benign breast disease without atypia but not with atypical hyperplasia or breast cancer. This association was not observed, however, when total fat intake was taken into account. Women with high levels of polyunsaturated fatty acids in adipose tissue and low serum or dietary levels of antioxidants were not observed to be at higher risk of breast cancer. CONCLUSIONS: Using an objective measure of intake, we observed no major associations between polyunsaturated fatty acids, including long-chain N-3 fatty acids and trans fatty acids, and risk of breast cancer or proliferative benign breast disease. IMPLICATIONS: These data do not support the hypothesis that intake of specific fatty acids, particularly polyunsaturated and trans fatty acids, is an important risk factor for malignant or benign breast disease.
BACKGROUND: We studied the associations between c-erbB-2 protein overexpression and p53 protein accumulation in benign breast tissue and the risk of subsequent breast cancer. METHODS: We conducted a case-control study nested within the cohort of 4888 women in the National Breast Screening Study (NBSS) who were diagnosed with benign breast disease during active follow-up. Case subjects were the women who subsequently developed breast cancer (ductal carcinoma in situ [DCIS] or invasive carcinoma). Control subjects were matched to each case subject on NBSS study arm, screening center, year of birth, and age at diagnosis of benign breast disease. Histologic sections of benign and cancerous breast tissues were analyzed immunohistochemically. Information on potential confounding factors was obtained by use of a self-administered lifestyle questionnaire. RESULTS: Accumulation of p53 protein was associated with an increased risk of progression to breast cancer (adjusted odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.01-6.40), whereas c-erbB-2 protein overexpression was not (adjusted OR = 0.65; 95% CI = 0.27-1.53). The findings for c-erbB-2 and p53 did not differ among strata defined by menopausal status, allocation within the NBSS, history of breast disease, and whether the benign breast disease was detected at a scheduled screen or between screens. The results were also similar after exclusion of case subjects whose diagnosis of breast cancer occurred within 1 year of their diagnosis of benign breast disease and after exclusion of subjects with DCIS. CONCLUSIONS: p53 protein accumulation, but not c-erbB-2 protein overexpression, appears to be associated with an increased risk of progression to breast cancer in women with benign breast disease.
Evidence from clinical follow-up studies has indicated that there is a relationship between the presence of histologically proven benign breast disease and breast cancer risk, and that the risk varies according to the histological category of benign breast disease and hormonal status. The risk associated with these histological factors appears to be equal in both breasts, suggesting that these factors are best considered markers of generalized increased breast cancer risk rather than direct precursor lesions. A number of interesting observations gleaned from the Nashville Study, the Breast Cancer Detection Demonstration Project and the Nurses' Health Study, among other studies, provide evidence of an interaction between these histological risk factors and estrogen in determining the level of breast cancer risk. In the National Surgical Adjuvant Breast Project P-1 trial, tamoxifen was associated with an 86% reduction in breast cancer risk among a small subset of women with biopsy-proven atypical hyperplasia. Taken together, these observations strongly suggest that there is an interaction between estrogen and histological factors in determining breast cancer risk, and that it may be possible to reduce the risk associated with these histological risk factors using antiestrogen therapy.
OBJECTIVE: The alteration of steroid hormonal status in premenopausal breast disease (benign and malignant) were investigated by comparing the urinary profile of androgens and corticoids. METHODS: The urinary concentrations of 25 androgens and corticoids were quantitatively determined by a gas chromatographymass spectrometry system in patients with benign breast disease (35 cases, 20-54 years), breast cancer (34, 27-54), and healthy controls of similar age (25, 22-51). RESULTS: In premenopausal patients with breast cancer, a significantly lower rate of excretion of 11-deoxy-17-ketosteroids and their metabolites was found in comparison with normal females. These levels were also inversely associated with benign breast disease. No significant differences were found between the three groups for the concentration of 11-oxy-17-ketosteroids, 17-hydroxy-corticoids and their metabolites. The urinary ratio of adrenal androgen metabolites to cortisol metabolites [(11-DOKS & M)/11-OKS] declined in the order of normal female control (4.04 +/- 0.72; mean +/- SD), breast benign mass (2.29 +/- 0.42) and breast cancer (0.94 +/- 0.27). CONCLUSION: Our data suggest that the hormonal imbalance of androgen deficiency and/or corticoid sufficiency is closely associated with the benign and malignant conditions of premenopausal breast disease and the ratio of (11-DOKS & M)/11-OKS may be an effective discriminant factor of these groups.
Breast health means more than breast cancer. At least 50% of patients seen at a multidisciplinary breast center have benign conditions. Pain, nipple discharge, and a question of a mass are the usual chief complaints. This article provides contemporary information and management guidelines for the common breast conditions associated with these complaints.