Predictors of breast cancer in women recalled following screening.

BACKGROUND: Established risk factors are associated with between 25 and 56% of breast cancer cases, but the relative importance and relevance to different age groups is unclear. METHODS: This case-control study examines established risk factors in 298 women with breast cancer and 1926 women without breast cancer aged 40-87 who were recalled for assessment following routine mammography. RESULTS: The cancer group were significantly older than the non-cancer group (F1,222 = 107.6; P < 0.0001). Postmenopausal obesity increased the odds of developing breast cancer (OR: 2.35; CI: 1.33-4.16). The breast cancer group were more likely to have used oral contraceptives (OR: 1.50; CI: 1.09-2.05), and women who used contraceptives for more than 10 years in total were at the highest risk (OR: 1.73; CI: 1.13-2.65). Daily consumption of alcohol was also associated with increased risk of developing breast cancer (OR: 1.62; CI: 1.13-2.33). Reproductive factors and a family history of breast cancer did not affect the odds of developing breast cancer and the reasons for these findings are explored. CONCLUSIONS: Results suggest that the effects of weight reduction in reducing postmenopausal breast cancer risk should be assessed.     

PREDICTORS OF BREAST CANCER IN WOMEN RECALLED FOLLOWING SCREENING

Background : Established risk factors are associated with between 25 and 56% of breast cancer cases, but the relative importance and relevance to different age groups is unclear. Methods : This case-control study examines established risk factors in 298 women with breast cancer and 1926 women without breast cancer aged 40–87 who were recalled for assessment following routine mammography. Results : The cancer group were significantly older than the non-cancer group (F_1,222 = 107.6; P < 0.0001). Postmenopausal obesity increased the odds of developing breast cancer (OR: 2.35; CI: 1.33–4.16). The breast cancer group were more likely to have used oral contraceptives (OR: 1.50; CI: 1.09–2.05), and women who used contraceptives for more than 10 years in total were at the highest risk (OR: 1.73; CI: 1.13–2.65). Daily consumption of alcohol was also associated with increased risk of developing breast cancer (OR: 1.62; CI: 1.13–2.33). Reproductive factors and a family history of breast cancer did not affect the odds of developing breast cancer and the reasons for these findings are explored. Conclusions : Results suggest that the effects of weight reduction in reducing postmenopausal breast cancer risk should be assessed.     

The Impact of Nutrition on the Development and Prognosis of Breast Cancer

SUMMARY: Breast cancer is the most frequent type of cancer in women. Recent data suggest that lifestyle factors including dietary factors play a significant role in the development of and survival from breast cancer. In particular, there is convincing evidence that obesity is a potent risk factor for both cancer development and prognosis, increasing the risk for overall and breast cancer mortality by approximately 30%. In contrast, there is still only limited evidence that specific dietary patterns or dietary components affect breast cancer outcomes. However, current knowledge suggests that a healthy/Mediterranean-like diet characterized by high intake of fruit, vegetables, fiber, fish and unsaturated oils, particularly n-3 fatty acids, has a modest protective effect on breast cancer, whereas a typical Western diet characterized by high intake of total/saturated fat, refined carbohydrates, processed and red meat and low fiber intake is associated with modestly poorer outcome. Based on this evidence, weight control is a key recommendation for primary and secondary prevention of breast cancer. Adherence to a healthy/Mediterranean-like diet and avoidance of a Western diet may confer additional, although still unproven, benefit.     

Rating the risk factors for breast cancer

OBJECTIVE: To update and summarize evidence of risk factors for breast cancer. SUMMARY BACKGROUND DATA: Women who are at high risk for breast cancer have a variety of options available to them, including watchful waiting, prophylactic surgery, and chemoprevention. It is increasingly important to accurately assess a patient's risk profile to ensure that the cost/benefit ratio of the selected treatment is favorable. METHODS: Estimates of relative risk for documented risk factors were obtained from seminal papers identified in previous reviews. These estimates were updated where appropriate with data from more recent reports using large sample sizes or presenting meta-analyses of previous studies. These reports were identified from a review of the Medline database from 1992 to 2002. RESULTS: Risk factors that have received a great deal of publicity (hormone use, alcohol consumption, obesity, nulliparity) present a relatively modest relative risk for breast cancer (<2). Factors associated with a prior history of neoplastic disease or atypical hyperplasia and factors associated with a genetic predisposition significantly affect the risk of breast cancer, with relative risks ranging from 3 (for some cases of positive family history) to 200 (for premenopausal women positive for a BRCA mutation). CONCLUSIONS: More precise tools, based on techniques of molecular biology such as microarray analysis, will be needed to assess individual risk for breast cancer.     

Position Paper of the American Council on Science and Health on Risk Factors for Breast Cancer: Established, Speculated, and Unsupported

Abstract: This article provides the position of the American Council on Science and Health regarding how breast cancer is defined and classified; the magnitude of the public health problem of breast cancer among women; the implications of variation in incidence of breast cancer internationally and with migration; access to health care as a factor in slight differences in incidence and mortality rates among African-American and white women; and the evidence concerning various proposed human-breast-cancer risk factors. The article classifies risk factors as either established, speculated, or unsupported on the basis of available evidence. Specific genes have been identified that may explain as much as 5–10% of new breast cancer cases. Inherited predispositions may be characterized by family history of breast or ovarian cancer, young age at diagnosis, breast cancer diagnosed in both breasts, and male breast cancer. Benign breast disease (BBD), particularly the subtypes of BBD involving atypical hyperplasia, and exposure early in life to ionizing radiation is an established risk factor for breast cancer. Several reproductive characteristics are established as risk factors for breast cancer: early age at menarche, first full-term pregnancy after age 35 years of late age, and late age of menopause. Obesity and low physical activity are established as risk factors for breast cancer and are modifiable. Speculated risk factors for breast cancer that are gaining scientific support include nulliparity, oral contraceptive use, and postmenopausal estrogen replacement therapy. Speculated risk factors for which there is conflicting or preliminary support include not breast feeding, postmenopausal estrogen/progestogen replacement therapy, prescribed diethylstilbestrol, low consumption of phytoestrogens, specific dietary practices, alcohol consumption, not using nonsteroidal antinflammatory drugs, abortion, and breast augmentation. Unsupported risk factors include higher than average consumption of phytoestrogens, premenopausal obesity, electromagnetic fields, and low-dose ionizing radiation after 40 years of age. There is only limited support for xenoestrogens and large breast size as risk factors for breast cancer.     

Breast cancer and ovarian cancer genetics

Breast and ovarian cancers are the second and fifth leading causes of cancer death, respectively, among women in the United States. Individuals with breast cancer have a 20--30% chance of having at least one relative with the disease. However, only 5--10% of the cases are a direct result of germline mutations in highly penetrable genes, such as BRCA1 and BRCA2 (BRCA1/2) as well as genes TP53 and PTEN. Since 1996, genetic testing for these mutations has been clinically available. A strategy for the management of women at increased familial risk of breast and ovarian cancers is described, which includes genetic assessment, chemoprevention, radiologic screening, and clinical and self-examination. Genetic testing should occur within a cancer genetic clinic after genetic counseling. A blood sample allows determination of the presence of the BRCA1 and BRCA2 genes, the TP53 gene, the PTEN gene, and the ATM gene. Tumor examination has identified a growth factor receptor gene, human epidermal growth factor receptor (HER-2).With regard to diet and lifestyle, women at increased risk of breast cancer could be advised to reduce dietary fat, avoid obesity, decrease alcohol consumption, and take regular exercise. Although chemoprotection is a valuable consideration, it is important to emphasize that the use of Tamoxifen in BRCA1 and BRCA2 mutation carriers is not established, nor is the optimum duration of benefit. An overview of the main outcomes of the current published studies confirms a 38% decrease in breast cancer incidence with Tamoxifen but recommends its use be restricted to women at high risk of breast cancer and low risk for potential side effects. The role of bilateral risk-reducing mastectomy or prophylactic mastectomy has been controversial for several reasons, including the psychosocial significance of the breast in Western cultures, the wide acceptance of breast conservation in surgery for early breast cancer, and the previous lack of data on its efficacy. The surgical procedure should aim to remove substantially all at-risk breast tissue. However, there is a balance between reduction of cancer risk and cosmetic outcome. Bilateral prophylactic oophorectomy can significantly decrease ovarian cancer risk in women who carry BCRA1 mutations. Oophorectomy lowers the risk of breast cancer, even in women who have previously used hormone replacement therapy. There are no published randomized controlled trials examining the effectiveness of mammographic screening in women under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer. under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer.     

Alcohol Drinking and Risk of Breast Cancer

Abstract: Using a case-control design, the authors studied female residents of five Massachusetts towns between 1983 and 1986. The objective was to measure the association between breast cancer occurrence and drinking alcohol. Cohort and case-control studies have often observed an association between drinking alcohol and breast cancer risk. In this study, women with any history of drinking alcohol had a risk of breast cancer 1.2-fold greater than women who never drank alcohol (95% confidence interval 0.7–1.8). The relative risk of breast cancer did not depend on the usual number of drinks per day or drinking history relative to time of diagnosis. Women who reported ever having a period of 6 months or more during which they drank more than average had an adjusted relative risk of breast cancer equal to 2.6 (95% confidence interval 1.1–5.8). The estimates of effect are consistent with the positive dose-response trends reported in a pooled analysis of large cohort studies and a meta-analysis of a broader spectrum of studies. Alcohol drinking remains one of the few risk factors for breast cancer amenable to intervention.     

代谢异常对结直肠癌发病的影响

代谢异常与结肠癌的发病有关.代谢综合征是一系列代谢异常症候群.目前国际定义的代谢综合征的几个关键因素,如腹型肥胖、血脂异常、血压升高、糖代谢异常,均与结直肠癌的发病相关.腹型肥胖与糖代谢异常可能是影响直肠癌发病的首要因素.在生理学上,内脏脂肪比皮下脂肪更活跃,并且能生成并分泌激素、细胞因子,参与炎症、代谢以及潜在致癌风险,因此,内脏脂肪的多少可能直接或间接地与结直肠癌的发生相关.肥胖可以通过高胰岛素血症、胰岛素样生长因子和脂肪细胞因子浓度的改变等几种机制增加结直肠癌发病的风险.上述代谢标志物不仅能够从病因学上进一步增进对结直肠癌的了解,也能够探索出与结直肠癌发病风险相关的新肥胖表型.     

Breast cancer risk in relation to alcohol consumption and BRCA gene mutations--a case-only study of gene-environment interaction

The variable penetrance of the BRCA1 and BRCA2 genes suggests that other genetic or environmental factors may interact with these mutations to modify breast cancer risk. The objective of this study was to measure departures from multiplicative effects of alcohol consumption and BRCA gene mutations. A cohort of French-Canadian breast cancer patients was tested for BRCA gene mutations and completed a food frequency questionnaire. The case-only odds ratio (COR) was calculated. A total of 857 women, including 10 BRCA1 and 33 BRCA2 mutation carriers, participated in the study. No significant interaction between alcohol consumption and BRCA1 mutations was detected, although the interaction with wine consumption suggested a sub-multiplicative effect (COR = 0.38, 95% CI: 0.08-1.81). Consumption of alcohol other than wine interacted significantly with BRCA2 mutations (COR = 2.15, 95% CI: 1.03-4.49). Consumption of wine may protect against BRCA1-associated tumors, while women with BRCA2 mutations may be at greater risk of alcohol-induced breast cancer.     

Fracture risk in women with breast cancer: a population-based study

A positive association has been reported between greater bone density and higher breast cancer risk, suggesting that these women could be at reduced risk of fracture. To estimate fracture risk among unselected community women with breast cancer and to systematically assess associations with various risk factors including breast cancer treatments, we conducted a population‐based historical cohort study of 608 Olmsted County, MN, USA, women with invasive breast cancer first diagnosed in 1990 to 1999 (mean age 61.6 ± 14.8 years), who were followed for 5776 person‐years. Altogether, 568 fractures were observed in 270 women (98 per 1000 person‐years). Overall fracture risk was elevated 1.8‐fold, but the absolute increase in risk was only 9%, and 56% of the women did not experience a fracture during follow‐up. Excluding pathologic fractures (15%) and those found incidentally (24%), to allow for ascertainment bias, the standardized incidence ratio was 1.2 (95% confidence interval [CI] 0.99 to 1.3) for total fracture risk and 0.9 (95% CI 0.7 to 1.2) for osteoporotic fracture risk alone. Various breast cancer treatments were associated with an increased risk of fracture, but those associations were strongest for pathologic fractures, which were relatively more common among the women who were premenopausal when their breast cancer was diagnosed. Moreover, underlying clinical characteristics prompting different treatments may have been partially responsible for the associated fracture outcomes (indication bias). These data thus demonstrate that breast cancer patients in general are not at greatly increased risk of fracture but neither are they protected from fractures despite any determinants that breast cancer and high bone density may have in common. © 2012 American Society for Bone and Mineral Research.     

Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system?

OBJECTIVES: To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1). Patients and methods In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smoking, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted. RESULTS: IGF-1 declined significantly by almost 25% among men aged >75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of -1.6 (- 2.2 to -0.9)% for an increment of one drink per day. There was no evidence for an effect of either smoking or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of -31.5 (- 49.1 to -7.9)% for an increment of one serving per day. CONCLUSIONS: The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system.     

Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers

Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrolment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70–0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71–1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.     

Risk factors for adult renal cell carcinoma

This study confirmed several independent risk and protective factors for RCC identified in the authors' previous study. Protective factors such as oral contraceptive use and moderate alcohol consumption were identified only in women. Tobacco consumption and severe obesity were the main independent risk factors. There were other modifiable risk markers, however, such as occupational exposure, thiazidic drug intake, and urinary tract infections. The associations between risk factors and RCC were weak, even for tobacco, for which the association was weaker than that for lung cancer. The identified risks involve a large proportion of the population, however, and the risk attributable to these types of exposure is high. The authors' recommendations for the prevention of RCC are therefore similar to those for the prevention of cardiovascular disease and cancer, and should be disseminated to the general population. The high-risk groups identified are too large for a specific early-screening program for RCC, but such screening might be appropriate if restricted to selected age groups.     

Diet and Breast Cancer: Can Dietary Factors Influence Survival?

Breast cancer accounts for over one third of invasive cancers in women. Earlier detection and improved initial treatments have resulted in an increasing number of women who have completed standard treatments but who remain at risk for breast cancer recurrence or early death. Epidemiological studies have linked diet composition with prognosis, and many women attempt to modify their diets and improve nutritional status following diagnosis. The hypothesis that dietary factors may reduce risk for secondary cancer events and increase survival in this population is currently under study in two large randomized clinical trials: the Women's Intervention Nutrition Study (WINS) and the Women's Healthy Eating and Living (WHEL) Study. The WHEL Study is testing the effect of a diet high in vegetables, fruit, and fiber, and low in fat, on disease-free survival in women with early stage breast cancer. Hypothesized mechanisms include effects of diet modification on gonadal hormones, retinoid-like activities of carotenoids, and other protective effects of biologically active dietary constituents.     

Diet, obesity, and prostate health: are we missing the link?

Prostate problems, such as benign prostatic hyperplasia, prostatic intra-epithelial neoplasia, prostatitis, and prostate cancer have been recognized as problems largely related to androgens and genetic factors. They affect a large fraction of the elderly population, contributing significantly to morbidity and mortality. Estrogen has also now been recognized as one of the important regulators of prostate growth. Diet, general health, and obesity were disregarded as the causative or complicating factors until very recently. Increasing episodes of prostate problems, complications in overweight/obese individuals, or both have attracted attention toward these contemporary risk factors. Prostate problems are reportedly less frequent or less severe in areas in which a plant-based diet is predominant. Consumption of certain fatty acids, particularly of animal origin, has been correlated with increased prostate problems. As adipose tissue is increasingly being regarded as hormonally active tissue, high body fat and obesity need in-depth exploration to understand the associated risk of prostate problems. Adipose tissue is now known to affect circulating levels of several bioactive messengers and therefore could affect the risk of developing prostate problems in addition to several other well-recognized health problems. Nevertheless, increased plasma volume, excess tissue growth, and fat deposition could affect resection and number of biopsies required, thus adding further complications because of a delayed diagnosis. In short, evidence is gathering to support the influence of diet and obesity on prostate health. In this review article, we have tried to make this connection more apparent using supporting published data.     

Alcohol Use Disorders Identification Test-consumption Predicts the Risk of Excessive Alcohol Consumption After Liver Transplantation

Excessive alcohol consumption has a negative impact on graft survival after liver transplantation (LT). However, it is difficult to predict alcohol relapse before LT. This study surveyed the alcohol consumption of LT recipients to identify the risk factors for harmful drinking. We surveyed the alcohol consumption of LT recipients by using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). AUDIT-C scores ≥ 5 points in men and ≥ 4 points in women indicated a high risk for harmful and hazardous drinking. Excessive alcohol consumption was considered to be > 20 g per day. Ninety-nine LT recipients completely filled out the questionnaire. Alcohol consumption after LT was detected in 26 recipients (26.5%); 4 of them had alcoholic liver disease before transplantation and 22 did not have alcoholic liver disease. The amount of alcohol consumption per day significantly decreased after LT (alcohol consumption per day: 49.6 g before LT vs 8.1 g after LT, P < .05). Fourteen recipients (14.1%) consumed alcohol excessively after LT. The AUDIT-C score before LT and smoking were risk factors for excessive alcohol consumption in the multivariate analysis. To properly manage post-transplant recipients, assessing the risk of excessive alcohol consumption by using the AUDIT-C is necessary.     

Prolactin and Breast Cancer Etiology: An Epidemiologic Perspective

A number of epidemiologic studies of prolactin and breast cancer etiology have recently become available. Retrospective case-control studies have suggested a modest positive or null relationship between circulating prolactin concentrations and risk of breast cancer. However these studies are limited by small sample sizes and the collection of blood after case diagnosis. Several large prospective studies, in which blood was collected prior to diagnosis, have observed modest positive associations between prolactin and risk. In a pooled analysis of ~80% of the world’s prospective data, the relative risk (RR) comparing women in the top vs bottom quartile of prolactin levels was 1.3 (95% confidence interval (CI): 1.1, 1.6, p-trend = 0.002). The results were similar for premenopausal and postmenopausal women. Most notably, high prolactin levels were associated with a 60% increased risk of estrogen receptor (ER) positive tumors, but not with ER negative tumors. Limited genetic data suggest a role of polymorphisms in the prolactin and prolactin receptor genes in risk of breast cancer. Studies of survival have suggested that high pretreatment prolactin levels were associated with treatment failure, earlier recurrence, and worse overall survival. Parity and certain medications are the only confirmed factors associated with prolactin levels in women. Overall, epidemiologic data suggest that prolactin is involved in breast cancer etiology. Further research to better elucidate these associations and their underlying mechanisms is warranted.     

Breast cancer: weighing up the dietary evidence

Evidence from migrant studies suggests the importance of environmental determinants in the aetiology of breast cancer. Of all dietary factors, fat intake has been the subject of the most intense debate over the past few decades, but the potential optimism from ecological studies has not been confirmed from prospective studies. Indeed, few if any strong correlations have been confirmed between dietary constituents and breast cancer. However, minor constituents of plant foods, like phytoestrogens, may potentially prove important in terms of breast cancer prevention. In this review the available evidence for dietary fat, antioxidant micronutrients, phytoestrogens, indole-3-carbinol and alcohol are addressed. A potentially protective role for plant foods requires further investigation and the results of prospective studies should clarify the relationships between dietary factors and breast cancer. Of critical importance in future research is further carefully controlled dietary intervention trials to examine in vivo the effects of minor dietary constituents on hormonal status and cell proliferation. A tentative recommendation would be to increase intakes of plant foods, and future research should lead to firmer conclusions to explain the striking international variability in breast cancer incidence rates.     

Management of women at increased risk for breast cancer secondary to high‐risk proliferative lesions and family history of the disease

Women with breast biopsies showing high‐risk proliferative lesions such as atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) have an increased risk of developing breast cancer. Other factors including age, family history of breast cancer, and extent of AH may play a role in increasing breast cancer risk. In addition to women with AH, there is a subset of women with a positive family history of breast cancer, without a known germline mutation, which places them also at an increased risk for breast cancer. Clinical management, screening, chemoprevention, and surgical risk‐reduction are discussed in this review to inform the management of these high‐risk women. Advanced imaging technology, pharmacologic research into different targets, and innovations in breast reconstruction are changing the way in which patients are counseled of their individual risk.     

Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies

We reviewed 37 prospective cohort and four intervention studies on potential dietary risk factors for prostate cancer, published between 1966 and September 2003. Some studies were limited by small size, crude measurement of dietary exposure and limited control for confounders. Intervention and prospective cohort studies support a protective role against prostate cancer for selenium, and possibly for vitamin E, pulses and tomatoes/lycopene. Overall consumption of meat, eggs, vegetables, fruit, coffee, tea, carotenoids and vitamins A, C and D was not consistently related to prostate cancer risk. Intervention studies also indicate that supplementation with beta-carotene does not lower prostate cancer risk, except possibly in men with low beta-carotene status at baseline. For specific types of meat, alcoholic drinks, dairy products, fat and anthropometric measures, most cohort studies suggest either an increased risk or no relation with prostate cancer. For calcium, two cohort studies suggest an increased risk at very high calcium intakes (>2000 mg/day). In conclusion, prospective studies are consistent with a protective role for selenium, and possibly vitamin E, pulses and tomatoes/lycopene, in the aetiology of prostate cancer. Studies are inconclusive on the role of meat, dairy products, fat, vegetables, fruits, alcohol and anthropometric measures, whereas a very high calcium intake appears to be positively associated with prostate cancer risk.