On the rumors about the silent spring. Review of the scientific evidence linking occupational and environmental pesticide exposure to endocrine disruption health effects

Occupational exposure to some pesticides, and particularly DBCP and chlordecone, may adversely affect male fertility. However, apart from the therapeutic use of diethylstilbestrol, the threat to human reproduction posed by "endocrine disrupting" environmental contaminants has not been supported by epidemiological evidence thus far. As it concerns other endocrine effects described in experimental animals, only thyroid inhibition following occupational exposure to amitrole and mancozeb has been confirmed in humans. Cancer of the breast, endometrium, ovary, prostate, testis, and thyroid are hormone-dependent, which fostered research on the potential risk associated with occupational and environmental exposure to the so-called endocrine-disrupting pesticides. The most recent studies have ruled out the hypothesis of DDT derivatives as responsible for excess risks of cancer of the reproductive organs. Still, we cannot exclude a role for high level exposure to o,p'-DDE, particularly in post-menopausal ER+ breast cancer. On the other hand, other organochlorine pesticides and triazine herbicides require further investigation for a possible etiologic role in some hormone-dependent cancers.     

Proportion of invasive breast cancer attributable to risk factors modifiable after menopause

A number of breast cancer risk factors are modifiable later in life, yet the combined impact of the population changes in these risk factors on breast cancer incidence is not known to have been evaluated. The population attributable risk (PAR) associated with individual risk factors and the summary PAR for sets of modifiable and nonmodifiable risk factors were estimated by using data on 3,499 invasive breast cancer cases and 4,213 controls from a population-based study in Wisconsin, Massachusetts, and New Hampshire, conducted from 1997 to 2001. The summary PAR for factors modifiable after menopause, including current postmenopausal hormone use, recent alcohol consumption, adult weight gain, and recent recreational physical activity, was 40.7%. Of the individual modifiable factors, the highest PARs were observed for weight gain (21.3%) and recreational physical activity (15.7%), which together showed a summary PAR of 33.6%. The summary PAR for factors not modifiable after menopause, including family history of breast cancer, personal history of benign breast disease, height at age 25 years, age at menarche, age at menopause, age at first birth, and parity, was 57.3%. These findings suggest that a substantial fraction of postmenopausal breast cancer may be avoided by purposeful changes in lifestyle later in life.     

Relationship of epithelial ovarian cancer to other malignancies within families

The relationship of family history of cancer of the breast, colon/rectum, cervix, endometrium, lung, and thyroid to the risk of epithelial ovarian cancer was investigated in a large population-based case-control study. The data consisted of family histories from 493 epithelial ovarian cancer cases and 2,465 controls aged 20-54 years. After controlling for potential confounders, risk for epithelial ovarian cancer was found to be significantly elevated among women reporting breast cancer and colo/rectal cancer in a first-degree relative. Adjusted odds ratios were 1.5 (95% CI = 1.1-2.1) and 1.9 (95% CI = 1.1-3.3), respectively. None of the remaining four types of cancer was found to be statistically associated with the risk of epithelial ovarian cancer. However, when histologic subtypes of epithelial ovarian cancer were considered, a family history of breast cancer was found to be associated with an elevated risk of endometrioid ovarian cancer (odds ratio = 2.3; 95% CI = 1.1-4.7), as was a family history of endometrial cancer (odds ratio = 2.7; 95% CI = 1.0-6.9). The results are considered in the context of other studies of familial patterns of cancer and are compared with published findings concerning the occurrence of multiple primary cancers in the same individual. The findings indicate that further study is warranted regarding possible genetic relationships between epithelial ovarian cancer and cancers arising in other organs.     

Influence of physical activity in different age and life periods on the risk of breast cancer.

We conducted a population-based case-control study of 1,237 incident breast cancer cases and 1,241 controls in Alberta between 1995 and 1997 to examine the effect of physical activity performed at different ages and life periods on breast cancer risk. In this study, we measured all types of physical activity done throughout life with a questionnaire developed and tested specifically for this study. We found that breast cancer risk was most associated with a risk reduction for activity done later in life, particularly between menopause and the reference year, for which we observed an odds ratio of 0.70 (95% confidence interval = 0.52-0.95). We also stratified the study participants into four categories according to their patterns of physical activity performed before and after menopause. For the women who sustained physical activity throughout life vs those who were never active, we found an odds ratio of 0.58 (95% confidence interval = 0.41-0.83). This study suggests that sustained activity throughout life and particularly activity done later in life may have the most benefit in reducing breast cancer risk.     

Assessing spatio-temporal variability of risk surfaces using residential history data in a case control study of breast cancer

Background  

Most analyses of spatial clustering of disease have been based on either residence at the time of diagnosis or current residence. An underlying assumption in these analyses is that residence can be used as a proxy for environmental exposure. However, exposures earlier in life and not just those in the most recent period may be of significance. In breast cancer, there is accumulating evidence that early life exposures may contribute to risk. We explored spatio-temporal patterns of risk surfaces using data on lifetime residential history in a case control study of breast cancer, and identified elevated areas of risk and areas potentially having more exposure opportunities, defined as risk surfaces in this study. This approach may be more relevant in understanding the environmental etiology of breast cancer, since lifetime cumulative exposures or exposures at critical times may be more strongly associated with risk for breast cancer than exposures from the recent period.     

Oral contraceptives and breast cancer

An attempt is made to summarize the results of recently conducted epidemiological studies relating to the possible adverse effects of oral contraceptives (OCs) on breast cancer. Evaluation of the safety of OCs is difficult. An important reason is that since preparations were introduced to the American market in 1959 the formulation of pills and the dosage of constituents have both changed markedly. A number of other considerations to be born in mind when evaluating the relevant literature were identified by a recent World Health Organization (WHO) Scientific Group. These include the following: there is usually a considerable latent period between 1st exposure to a carcinogen and the development of overt malignancy; and it is possible that exposure to contraceptive steroids may be particularly important at certain critical periods during reproductive life. After age, the most important risk factors during early life are a young age at menarche and a late age at 1st full term birth. There factors appear to operate independently and so the longer the period between menarche and 1st full term birth, the higher is the risk of breast cancer. A girl whose menarche occurs before age 12 is approximately twice as likely to develop breast cancer later in life as a girl whose menarche occurs after age 14. Similarly, a woman whose first full term birth occurs after age 35 is about 3 times more likely to develop breast cancer than a woman who gives birth before age 20. Nulliparous women have an intermediate risk. Other known risk factors include a family history of breast cancer, a past history of benign breast disease, and increased body weight. Possibly the most serious problem from an epidemiological perspective is the interrelationship between calendar time, age, and OC exposure. OC seems to be clearly associated with a decreased risk of benign breast disease of sufficient severity to require biopsy and the evidence is that the reduction in risk increases with duration of use. The epidemiological evidence available regarding OCs and breast cancer is reassuring. Data have been obtained from case control studies and cohort studies. A table summarizes the main features of 12 case control studies. Results of both groups of studies are reassuring in relation to breast cancer, yet there is usually a long period between exposure to a carcinogen and the development of overt malignancy and OCs have been in widespread use for only a relatively short time. Women who have never used OCs seem to present with more clinically advanced tumors than women who have used them. The differences in staging are reflected in patterns of survival. The difference may be due to a greater awareness of breast disease in OC users, but it could represent a beneficial biological effect of OCs.     

Factors Modifying the Association Between Hormone-Replacement Therapy and Breast Cancer Risk

Objectives: Hormone-replacement therapy (HRT) is an established risk factor for breast cancer. HRT users are different from non-users with respect to socio-economic and other characteristics. There may be women where the HRT-related risk could be modulated by other factors.Methods: We conducted a population-based case–control study with 688 breast cancer cases and 724 controls to characterize HRT users and to estimate odds ratios (OR) and 95% confidence intervals (CI) for HRT use and potentially risk modifying factors. Results: In women aged 50 years and older, 58% of controls and 61% of cases ever used HRT. Among women in natural menopause, HRT use for 10 years and more years was associated with an increased breast cancer risk (OR 1.79, 95% CI, 1.12–2.87), but not among women in surgical menopause (OR 0.61, 95% CI, 0.09–4.17). In the subgroup of women with a positive family history of breast cancer, each year of HRT use increased the risk by 1.22 (95% CI, 1.02–1.47). Another subgroup comprised women with at least 10 diagnostic mammograms (OR 4.04, 95% CI, 1.10–14.81 for using HRT 10 or more years).Conclusions: Long-term HRT use was associated with a breast cancer risk in women with natural menopause. Our findings suggest that this risk may be increased in women with a positive family history of breast cancer and in women who received frequent diagnostic mammographic screens.     

Milk Intake in Early Life and Later Cancer Risk: A Meta-Analysis

Dairy consumption in adulthood has been demonstrated to influence cancer risk. Although childhood and adolescence represent critical periods of rapid growth, the relationship between milk intake in early life and later cancer risk is unclear. Thus, we examined this relationship by conducting a meta-analysis of the observational studies. PubMed and Embase were searched for relevant articles that were published throughout December 2021. The summary relative risk (RR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The summary RR for the highest vs. lowest milk intake was 0.83 (95% CI = 0.69–1.00; p = 0.05; I² = 60%; seven studies) for breast cancer, 0.98 (95% CI = 0.72–1.32; p = 0.88; I² = 51%; four studies) for prostate cancer, and 0.90 (95% CI = 0.42–1.93; p = 0.78; I² = 83%; three studies) for colorectal cancer. No evidence of an association emerged in subgroup analyses of menopausal status, cancer stage, fat content of milk, life stage of milk intake, or study design. Consistent results were observed in the meta-analyses using total dairy intake. In conclusion, milk intake during childhood and adolescence might not be associated with risks of breast, prostate, and colorectal cancer later in life. Given the small number of studies that were included in our meta-analysis, and the high heterogeneity, more studies are warranted for a definitive conclusion.     

Impact of prenatal arsenic exposure on chronic adult diseases

ABSTRACT

Exposure to environmental stressors during susceptible windows of development can result in negative health outcomes later in life, a concept known as the Developmental Origins of Health and Disease (DOHaD). There is a growing body of evidence that exposures to metals early in life (in utero and postnatal) increase the risk of developing adult diseases such as cancer, cardiovascular disease, non-alcoholic fatty liver disease, and diabetes. Of particular concern is exposure to the metalloid arsenic, a drinking water contaminant and worldwide health concern. Epidemiological studies of areas with high levels of arsenic in the drinking water, such as some regions in Chile and Bangladesh, indicate an association between in utero arsenic exposure and the development of adult diseases. Therefore, the need for experimental models to address the mechanism underlining early onset of adult diseases have emerged including the in utero and whole-life exposure models. This review will highlight the epidemiological events and subsequent novel experimental models implemented to study the impact of early life exposure to arsenic on the development of adult diseases. In addition, current research using these models will be discussed as well as possible underlying mechanism for the early onset of disease.

Abbreviations: ALT: alanine aminotransferase; AMI: acute myocardial infarction; AST: aspartate aminotransferase; ATSDR: Agency for Toxic Substances and Disease Registry; CVD: cardiovascular disease; DMA: dimethylarsinate; DOHaD: Developmental Origins of Health and Disease; EPA: U.S. Environmental Protection Agency; ER-α: estrogen receptor alpha; HDL: high-density lipoprotein; HOMA-IR: homeostatic model assessment of insulin resistance; iAs: inorganic arsenic; LDL: low-density lipoprotein; MetS: metabolic syndrome; MMA: monomethylarsonate; NAFLD: non-alcoholic fatty liver disease; PND: postnatal day; ppb: parts per billion; ppm: parts per million; SAM: S-adenosylmethionine; USFDA: United States Food and Drug Administration     

Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women

Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR?=?0.41; 95% CI: 0.29–0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.     

乳腺癌主要危险因素的流行趋势与一级预防

近年来我国乳腺癌发病率不断上升,严重威胁妇女的生命健康。生活方式与生育因素是乳腺癌发病风险增加的主要原因。研究生活方式和生育两方面的因素与乳腺癌的关系,以及这些因素近年来在我国妇女人群中的流行变化趋势和现开展的预防措施或策略进行梳理,为评估人群归因风险、推进乳腺癌一级预防进程提供参考依据。     

Early growth and obesity risk – What should health professionals be advising?

Obesity rates in the UK have been continuously increasing among adults and children and have been attributed to nutritional and lifestyle practices that promote a positive shift in energy balance. Over the last few decades, a growing body of evidence suggests that the origins of obesity start at the earliest stages of human development and specifically pre‐conception, in utero and during early infancy. Maternal nutritional status and early life feeding have been identified as ‘critical windows’ for obesity risk. Pre‐conception and pregnancy overweight and obesity, as well as fetal exposure to diabetes and hyperglycaemia, have been associated with high birthweight, which, in turn, has been reported to have a direct link with obesity risk later in life. A number of studies have also demonstrated low birthweight to be associated with increased risk of obesity and suggested that low‐birthweight term infants who demonstrate early ‘catch‐up’ growth have a tendency to become obese adults. Low birthweight has been associated with pre‐conception underweight and inadequate in utero nutrition. Although the links between early growth and later obesity risk implicate maternal pre‐natal nutrition, it has been suggested that nutrition during early infancy also affects later body composition. Breastfeeding has been associated with a reduced prevalence of obesity, although the evidence is still inconsistent and somewhat limited. Recent advances in the ability to manipulate infant formula composition by reducing its protein content and bringing its composition closer to that of breastmilk could potentially help prevent the rapid weight gain observed in formula‐fed infants. Early introduction of complementary foods has also been associated with increased obesity risk later in life. Unfortunately to date, the majority of evidence on the developmental origins of obesity comes from observational studies, making their interpretation difficult and providing an uncertain basis for practice. However, a number of modifiable risk factors in the pre‐natal and early post‐natal periods of human development have been identified, as well as vulnerable subgroups within the population to these risk factors, which may guide health professionals when advising women regarding lifestyle strategies to reduce the risk of obesity for their offspring and for future generations.     

Predictors of Breast Cancer Screening in a Panel Study of African American Women

ABSTRACT

Purpose: This study examines the predictors of breast cancer screening participation in a panel study of African American women over age 40. We examine the effect of depression, age, beliefs and concerns about breast cancer and its risk, communication with social networks regarding screening, marital status, participation in religious organizations, breast cancer family history, and participation in a breast cancer education program.

Methods: Participants were recruited from 30 African American churches, two low-income housing projects, and from a health fair at a historically African American University (N = 364). Participants were interviewed upon recruitment, and three months later. Multinomial logistic regression models are estimated to assess the relative impact of covariates on the odds of getting a mammogram while controlling for other factors. We also assess predicted probabilities of screening at specific levels of covariates.

Results: We find that age, marriage, an educational intervention, talking with friends, and believing that early detection can lead to cure had a positive impact on getting a mammogram between T1 and T2. In contrast, depression significantly reduces the odds of getting a mammogram. Family histories of breast cancer and church participation have no effect on rates of mammography net of other factors.     

Association between family history of cancer and breast cancer defined by estrogen and progesterone receptor status

There are recent data to suggest that risk factors for breast cancer may differ according to whether the tumor expresses detectable levels of the estrogen receptor (ER) and progesterone receptor (PR). While a family history of breast cancer is one of the most consistent predictors of the disease, we recently reported a modest inverse association with ER+PR− tumors. However, the definition of a family history of cancer did not consider second-degree relatives or cancer sites that may be etiologically related. The current report presents additional data analysis from the Iowa Women's Health Study, a prospective population-based cohort study conducted among 41,837 postmenopausal women. At baseline in 1986, respondents provided information on family history of cancers of the breast, ovaries, or uterus/endometrium in their mothers, sisters, daughters, maternal and paternal grandmothers, and maternal and paternal aunts. Data on family history of prostate cancer in fathers and brothers and age at onset of breast cancer in mothers and sisters were collected in 1992. Cohort members were followed for cancer incidence through the statewide tumor registry. After 7 years and more than 235,000 person-years of follow-up, 939 incident cases of breast cancer were identified. Information was obtained from the tumor registry on ER (+/−) and PR (+/−) status for 610 cases (65.0%). A family history of breast cancer in first-degree relatives was associated with increased risk (relative risk [RR] = 1.4; 95% confidence interval [CI]: 1.1–1.6) for all receptor-defined subtypes of breast cancer except ER+PR− tumors (RR = 0.7; 95% CI: 0.3–1.4). These results were unchanged when data on second-degree relatives were included. When the onset of breast cancer in relatives occurred at or before the age of 45 years, increased risks were evident only for ER−PR+ and ER−PR− tumors (RR = 2.3 and 3.3, respectively). Conversely, when relatives were affected with breast cancer after the age of 45 years, increased risks were most apparent for ER+PR+ and ER−PR+ tumors (RR = 1.3 and 3.2, respectively). A family history of prostate cancer in first-degree relatives was associated with a 1.2-fold increased risk of breast cancer (95% CI: 0.98–1.50), largely a reflection of the association with ER−PR− tumors (RR = 1.5; 95% CI: 0.8–3.0). The small numbers of cases in some categories and the corresponding wide CIs preclude definitive conclusions, but these data are at least suggestive that joint stratification of breast tumors on ER and PR status may be useful in partitioning breast cancer families into more homogeneous subsets. © 1996 Wiley-Liss, Inc.     

Epidemiologic evidence suggests that dietary phytoestrogen intake is associated with reduced risk of breast, endometrial, and prostate cancers

Phytoestrogens are natural estrogen-like plant substances. The possible protective effect of phytoestrogens on cancer risk, particularly on hormone-related cancers, has been the focus of many epidemiologic studies during the last 2 decades. We performed a qualitative review of the epidemiologic literature published in the English language and identified on MEDLINE from 1966 until 24 September 2006 on (1) dietary intake of soy, isoflavones, or lignans; (2) urinary excretion of isoflavones or lignans; (3) blood measurements of isoflavones or lignans in relation to breast, prostate, and endometrial cancer risk. Epidemiologic data do seem to support a small protective effect of isoflavones on breast cancer risk, although timing of exposure and the mechanisms of isoflavones at physiologic levels need to be further explored. The epidemiologic evidence to date is conflicting regarding lignans and breast cancer, but recent studies suggest that the effect may be restricted to premenopausal women, differ by estrogen receptor status, and be modified by diet-gene interactions. The 3 case-control studies on dietary intake of phytoestrogens and endometrial cancer risk have provided some evidence for a protective effect, but more prospective data are needed. There is some epidemiologic evidence for a protective effect of soy or isoflavones on prostate cancer, but corresponding data for lignans are inconclusive. Recent data indicate that diet-gene interactions may modify the effect of phytoestrogens on prostate cancer risk. Prospective studies on dietary lignans in relation to prostate cancer risk are lacking.     

Preeclampsia and breast cancer risk.

Breast cancer is associated with endogenous hormone levels, but the exact relation and underlying mechanisms remain unclear. Data from several recent epidemiologic studies suggest that a woman who experiences preeclampsia in her own pregnancy, or who was herself born to a preeclamptic pregnancy, is at reduced risk for breast cancer later in life. This paper reviews the evidence for a connection between preeclampsia and breast cancer risk, and discusses the hormonal mechanisms that might explain this association. Preeclampsia is characterized by reduced levels of estrogens and insulin-like growth factor-1, and by elevated levels of progesterone, androgens, human chorionic gonadotropin, IGF-1 binding protein, corticotropin-releasing factor, cortisol, and insulin. These factors may act both individually and synergistically to decrease breast cancer risk. The occurrence of preeclampsia during a woman's pregnancy may reflect an underlying hormonal profile that both predisposes her to preeclampsia and reduces her risk for breast cancer. In addition, the major hormonal alterations associated with preeclampsia during gestation may have lasting effects on subsequent breast cancer risk. Finally, the hormonal and nutritional environment of the womb, for which preeclampsia is a marker, may play an important role in programming lifelong risk for breast cancer in the female offspring.     

State of the Evidence: The Connection Between Breast Cancer and the Environment

Abstract

A substantial body of scientific evidence indicates that exposures to common chemicals and radiation, alone and in combination, are contributing to the increase in breast cancer incidence observed over the past several decades. Key recurring themes in the growing scientific literature on breast cancer and environmental risk factors are: (a) the importance of understanding the effects of mixtures and interactions between various chemicals, radiation and other risk factors for the disease; and (b) the increasing evidence that timing of exposures matters, with exposures during early periods of development being particularly critical to later risk of developing breast cancer. A review of the scientific literature shows several classes of environmental factors have been implicated in an increased risk for breast cancer, including hormones and endocrine-disrupting compounds, organic chemicals and by-products of industrial and vehicular combustion, and both ionizing and non-ionizing radiation.     

Influence of Nativity Status on Breast Cancer Risk Among US Black Women

Black women are at increased risk for breast cancer mortality. The black category is assumed to be homogeneous, an assumption that may be misleading. This study aims to examine the relationship between nativity and breast cancer risk factors among women identified as black. A sample of 236 black women over 18 years of age in Brooklyn, New York, was recruited. Data were collected on race/ethnicity, breast cancer risk factors, and other sociodemographic, behavioral, and early life experience factors. Logistic regression analyses were used to estimate prevalence ratios for association between nativity and breast cancer risk factors. US-born blacks were more likely to be unemployed, smoke, not breastfeed, and breastfeed for a shorter duration than foreign-born blacks (all p≤0.01). Foreign-born blacks were more likely to have parents who achieved at least a high school education (p<0.05). After adjustment for smoking, employment, and parental education, US-born blacks were twice as likely to never breastfeed (PR 2.2, 95% CI: 1.1, 4.46) compared to foreign-born blacks. Among women who breastfed, US-born blacks were also less likely to breastfeed for 6–11 months or more than 12 months, but these associations were not statistically significant. Because lactation reduces breast cancer risk and is a leading modifiable risk factor, understanding its variation within black women will help physicians and public health practitioners to target patient counseling and education of breast cancer risk. Borrell, Castor, and Terry are with the Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Conway is affiliated at Adelphi University, New York, NY, USA.     

An Updated Comprehensive Review on Vitamin A and Carotenoids in Breast Cancer: Mechanisms,Genetics, Assessment,Current Evidence,and Future Clinical Implications

Vitamin A and carotenoids are fat-soluble micronutrients that play important role as powerful antioxidants modulating oxidative stress and cancer development. Breast cancer is the most common malignancy in women. As the risk of breast cancer is dependent on various lifestyle factors such as dietary modifications, there is increasing interest surrounding the anti-cancerous properties of vitamin A and carotenoids. Despite the suggested protective roles of vitamin A and carotenoids in breast cancer development, their clinical application for the prevention and treatment of breast cancer is limited. In this narrative review, we discuss the roles of vitamin A and carotenoids along with the evaluation method of vitamin A status. We also exhibit the association of genetic variations involved in metabolism of vitamin A and carotenoids with cancers and other diseases. We demonstrate the epidemiological evidence for the relationship of vitamin A and carotenoids with breast cancer risk, their effects on cancer mechanism, and the recent updates in clinical practice of vitamin A or carotenoids as a potential therapeutic agent against breast cancer. This review provides insight into the preventive and therapeutic roles of vitamin A and carotenoids in breast cancer development and progression.     

Breast cancer and the consumption of coffee

The hypothesis has been raised that coffee consumption may increase the incidence of breast cancer, based on the report that fibrocystic breast disease, a risk factor for breast cancer, regresses after abstention from coffee and other methylxanthines. The relation between recent coffee consumption and the risk of breast cancer was evaluated in a case-control study, based on interviews conducted 1975-1982 at several mainly eastern US teaching and community hospitals. The responses of 2,651 women with newly diagnosed breast cancer were compared with those of 1,501 controls with nonmalignant conditions and 385 controls with cancers at other sites. The relative risk estimates for levels of coffee drinking up to seven or more cups daily, relative to none, approximated 1.0 with narrow 95% confidence intervals. After allowance for confounding, the relative risk estimate for drinking at least five cups a day was 1.2 (95% confidence interval, 0.9-1.6) using the noncancer controls and 1.1 (0.7-1.6) using the cancer controls. Coffee consumption was not associated with an increase in the risk of breast cancer among women with a history of fibrocystic breast disease, nor were tea or decaffeinated coffee associated with an increase in the risk of breast cancer. The results suggest that the recent consumption of coffee does not influence the incidence of breast cancer.