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PubMed1977

Epidemiology of endometrial cancer.

For a population-based, case-control study of cancer of the endometrium in Greater Boston from 1965 through mid-1969, 440 cases were drawn from nearly all hospitals in the area; controls were drawn at random from the general population. The age-adjusted incidence rate was 18.1/100,000 woman-years, with a peak at ages 55-59 and a gradual decline thereafter. Information was provided from 212 cases and 1,198 controls by mall questionnaire. A trend of reduced risk of endometrial cancer with increased parity was noted, the relative incidence (RI) for multiparous women being 0.3 compared to a RI of unity for married nulliparous women. The association of risk with age at first birth was irregular. Early menarche (RI=1.6) and late menopause (RI=1.7) were associated with increased risk of disease. Endometrial cancer risk was also found to be directly related to socioeconomic status, relative weight, diabetes, hypertension, and arthritis. The findings supported the idea that hormone activity during, and perhaps after, reproductive life is an important cause of this disease.

Adenocarcinoma↗
PubMed1984

Incidence of vulvar carcinoma in relation to menstrual, reproductive, and medical factors.

Fifty-seven female residents of King and Pierce Counties (Washington State) with a new diagnosis of in situ or invasive vulvar carcinoma during 1976-79 were interviewed concerning their menstrual, reproductive, and medical histories. A random sample of women residing in the same area was interviewed for comparison. A greater proportion of women with in situ vulvar tumors than control subjects were of low educational level, reported a history of oral contraceptive use, experienced early age at first birth, late age at menopause, and were current or former cigarette smokers. Menstrual and reproductive factors were similar between women with invasive vulvar cancer and controls, but a greater proportion of cases reported a history of diabetes and of cigarette smoking. The factors found in this study to be associated with in situ vulvar carcinoma are similar to those observed among women with cervical cancer. In addition, since the vulva and cervix both are derived from cloacal tissue, and neoplasms of the two sites occur together more often than would be expected by chance, in situ vulvar and cervical tumors may share some common etiologies.

Adult↗
PubMed1994

Validation of the Gail et al. model for predicting individual breast cancer risk.

BACKGROUND: The Gail et al. model is considered the best available means for estimating an individual woman's risk of developing breast cancer. Such estimates are useful in decision making on the part of women, in designing prevention trials, and in targeting screening and prevention efforts. PURPOSE: Our purpose was to evaluate the ability of the model to accurately predict individual breast cancer risk, using a large population independent of the one from which the model was derived. METHODS: We compared the number of cancer cases predicted by the model to the actual number of cases observed in the Nurses' Health Study. The study population was 115,172 women who did not have breast cancer at the beginning of the study. Questionnaires were sent to participants every 2 years, seeking data on risk factors and diagnoses of breast cancer. Follow-up compliance was 95% over the 12-year study period. RESULTS: The model over-predicted absolute breast cancer risk by 33% (95% confidence interval [CI] = 28%-39%), with the overprediction more than twofold among premenopausal women (95% CI = 1.9-2.2), among women with extensive family history of breast cancer (95% CI = 1.1-3.9), and among women with age at first birth younger than 20 years (95% CI = 1.3-4.7). The correlation coefficient between observed and predicted risk was 0.67, indicating that the model is less than satisfactory for ranking individual levels of breast cancer risk. Overprediction occurred at all deciles of predicted risk. CONCLUSIONS: The model's performance is unsatisfactory for estimating breast cancer risk for individual women aged 25-61 years who do not participate in annual screening. Lower mammography screening rates in the Nurses' Health Study may account for some, but not all, of the discrepancy between observed and predicted cases. IMPLICATIONS: A recent modification of the model by the tamoxifen trial investigators is likely to have provided accurate power calculations. This modified form of the model should be useful for planning other large, population-based studies.

Adult↗
PubMed1995

Mammographic features and breast cancer risk: effects with time, age, and menopause status.

BACKGROUND: Mammographic images from women with a high proportion of epithelial and stromal breast tissues are described as showing high-density parenchymal patterns. Most past studies that noted an increase in breast cancer risk associated with mammographic parenchymal patterns showing high density either 1) lacked information on other breast cancer risk factors, 2) were too small, or 3) included insufficient follow-up time to adequately resolve persisting doubts whether mammographic features are "independent" measures of breast cancer risk and not a detection artifact. PURPOSE: The purpose of this study was twofold: 1) to evaluate the associations between mammographic features and other breast cancer risk factors and 2) to assess effects of mammographic features on breast cancer risk by time, age, and menopause status. METHODS: To address these questions, we analyzed detailed information from a large, nested case-control study with 16 years of follow-up. This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project, a nationwide program that offered annual breast cancer screening for more than 280,000 women from 1973 to 1980. Mammographic features were assessed from the base-line screening mammographic examination for 1880 incident case subjects and 2152 control subjects. Control subjects were randomly selected from women of the same age and race as each case subject. Control subjects attended the same screening center as the case subject and were free of breast cancer at the case subject's date of diagnosis. Odds ratios (ORs) with 95% confidence intervals (CIs) provided estimates of the relative risk of breast cancer. RESULTS: Mammographic features were associated with known breast cancer risk factors. However, the high-density parenchymal pattern effects were independent of family history, age at first birth, alcohol consumption, and benign breast disease. The increase risk for women with Wolfe's two high-density parenchymal patterns, P2 (OR = 3.2; 95% CI = 2.5-4.0) and Dy (OR = 2.9; 95% CI = 2.2-3.9), was explained primarily by measured percent of the breast with dense mammographic appearance. Compared with women with no visible breast density, women who had a breast density of 75% or greater had an almost fivefold increased risk of breast cancer (95% CI = 3.6-7.1). These effects persisted for 10 or more years and were noted for both premenopausal and postmenopausal women of all ages. CONCLUSIONS: Of the breast cancer risk factors assessed in the participants, high-density mammographic parenchymal patterns, as measured by the proportion of breast area composed of epithelial and stromal tissue, had the greatest impact on breast cancer risk. Of the breast cancers in this study, 28% were attributable to having 50% or greater breast density.

Age Factors↗
PubMed1997

Intrauterine environment and breast cancer risk in women: a population-based study.

BACKGROUND: The established risk factors for female breast cancer, including nulliparity, age at first birth, age at menarche, and age at menopause, do not adequately explain the occurrence pattern of this cancer. Therefore, additional factors need to be considered to advance our understanding of the causes of breast cancer. Evidence obtained from animals and humans indicates that the perinatal period may be particularly important. Our earlier studies, based on a subsample of the present investigation, suggested that factors thought to be positively associated with estrogen levels during pregnancy are positively associated with breast cancer risk. However, the associated confidence intervals (CIs) were generally wide, indicating considerable variability in the data. PURPOSE: We studied a large number of incident breast cancer case patients and evaluated several perinatal variables in relation to breast cancer risk. These variables included some not previously studied, such as gestational age and neonatal jaundice. We also investigated twin membership as a predictor variable and death from breast cancer, in addition to occurrence of breast cancer, as an alternative outcome variable. METHODS: Birth records for all deliveries at five different hospitals in Sweden during the period from 1874 through 1961 were used to define a large cohort of women. Incident case patients with breast cancer in this cohort were ascertained through the National Cancer Registry or the Uppsala Regional Cancer Registry from 1958 through 1994. In a case-control study nested in the cohort, we abstracted data from birth records on 1068 women with incident breast cancer and on 2727 control subjects individually matched to the case patients on date of birth. We modeled the data through conditional logistic regression. All P values were derived from two-sided statistical tests. RESULTS: We found a markedly reduced risk for breast cancer in women whose mothers had pregnancy toxemia (odds ratio [OR] = 0.41; 95% CI = 0.22-0.79) and an excess risk on women who had neonatal jaundice (OR = 2.16; 95% CI = 1.27-3.67) or who were born before 33 weeks of gestation (OR = 3.96; 95% CI = 1.45-10.81). Compared with the risk for breast cancer in the singleton, the risk for breast cancer in dizygotic twins was increased, although this increase was not statistically significant (OR = 1.72; 95% CI = 0.92-3.20). There was no evidence in these data for a statistically significant or substantial association of breast cancer risk with birth size indicators (i.e., weight and length at birth and placental weight). CONCLUSION AND IMPLICATIONS: Because pregnancy toxemia is associated with low levels of estrogens and neonatal jaundice, severe prematurity, and dizygotic twins with high levels of estrogens, our findings suggest that estrogens and other hormonal factors, known to influence breast cancer risk in the adult, may also play a critical role during the intrauterine period.

Breast Neoplasms↗
PubMed2005

Alcohol and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status: a prospective cohort study.

BACKGROUND: Alcohol intake has been reported to be positively associated with an increased risk of postmenopausal breast cancer; however, the association with the estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors remains unclear. METHODS: Self-reported data on alcohol consumption were collected in 1987 and 1997 from 51,847 postmenopausal women in the population-based Swedish Mammography Cohort. Through June 30, 2004, 1188 invasive breast cancer case patients with known ER and PR status were identified during an average 8.3-year follow-up. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of breast cancer, adjusting for age; family history of breast cancer; body mass index; height; parity; age at menarche, first birth, and menopause; education level; use of postmenopausal hormones; and diet. Heterogeneity among groups was evaluated using the Wald test. All statistical tests were two-sided. RESULTS: Alcohol consumption was associated with an increased risk for the development of ER-positive (+) tumors, irrespective of PR status (highest intake [> or = 10 g of alcohol per day] versus nondrinkers, multivariable RR = 1.35, 95% confidence interval [CI] = 1.02 to 1.80; Ptrend < .049 for ER+PR+ tumors; and RR = 2.36, 95% CI = 1.56 to 3.56; Ptrend < .001 for ER+PR-tumors). The absolute rate of ER+ breast cancer (standardized to the age distribution of person-years experienced by all study participants using 5-year age categories) was 232 per 100,000 person-years among women in the highest category of alcohol intake, and 158 per 100,000 person-years among nondrinkers. No association was observed between alcohol intake and the risk of developing ER-tumors. Furthermore, we observed a statistically significant interaction between alcohol intake and the use of postmenopausal hormones on the risk for ER+PR+ tumors (Pinteraction = .039). CONCLUSION: The observed association between risk of developing postmenopausal ER+ breast cancer and alcohol drinking, especially among those women who use postmenopausal hormones, may be important, because the majority of breast tumors among postmenopausal women overexpress ER.

Aged↗
PubMed1997

Breast cancer clusters in the northeast United States: a geographic analysis.

High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia, Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors.

Breast Neoplasms↗
PubMed1999

Low-weight neonatal survival paradox in the Czech Republic.

Analysis of vital statistics for the Czech Republic between 1986 and 1993, including 3,254 infant deaths from 350,978 first births to married and single women who conceived at ages 18-29 years, revealed a neonatal survival advantage for low-weight infants born to disadvantaged (single, less educated) women, particularly for deaths from congenital anomalies. This advantage largely disappeared after the neonatal period. The same patterns have been observed for low-weight infants born to black women in the United States. Since the Czech Republic had an ethnically homogenous population, virtually universal prenatal care, and uniform institutional conditions for delivery, Czech results must be attributed to social rather than to biologic or medical circumstances. This strengthens the contention that in the United States, the black neonatal survival paradox may be due as much to race-related social stigmatization and consequent disadvantage as to any hypothesized hereditary influences on birth-weight-specific survival.

Adolescent↗
PubMed1999

Risk factors for coronary heart disease in African American women.

There have been few studies of risk factors for coronary heart disease in African American women. The authors investigated factors associated with prevalent coronary heart disease in data provided by participants in the Black Women's Health Study. In 1995, 64,530 US Black women aged 21-69 years completed postal health questionnaires. The 352 women who reported having had a heart attack (cases) were frequency matched 5:1 on age with 1,760 women who had not (controls); medical record review for 35 cases indicated that two-thirds had had a heart attack and the remainder had other coronary heart disease. Odds ratios, obtained from multiple logistic regression analyses, were significantly elevated for cigarette smoking, drug-treated hypertension, drug-treated diabetes mellitus, elevated cholesterol level, and history of heart attack in a parent. High body mass index (kg/m2) was associated with coronary heart disease in the absence of control for hypertension, diabetes mellitus, and elevated cholesterol but not when they were controlled, suggesting that obesity may influence risk as a result of its effects on blood pressure, glucose tolerance, and cholesterol levels. Odds ratios increased with increasing parity and with decreasing age at first birth. These data suggest that important risk factors for coronary heart disease are similar in Black women and White women.

Adult↗
PubMed1978

Incidence rates and risk factors of benign breast neoplasms.

A case-control study of benign breast disease was conducted in Greater Boston in 1968-1969. Cases were nearly all women living in the reference population who were initially diagnosed as having fibrocystic disease, fibroadenoma or a "mixed" lesion during the study period. Controls were a random sample of the entire reference population. A mail questionnaire was completed for 678 cases and for 1807 controls. For fibrocystic disease the age-standardized incidence rate was 89.4 per 100,000 woman-years; for fibroadenoma it was 32.8. Fibrocystic disease rises in incidence to age 45 and then declines sharply. The incidence rate of fibroadenoma peaks during the 20's, while that of mixed tumors has a mode at 30 to 34. Among young women, the highest rates occur in married nulliparae, but this is not so at higher ages. Neither for fibroadenoma nor fibrocystic disease was there a consistent relationship of risk with parity or with age at first birth. Fibrocystic disease risk was strongly and directly related to age at natural menopause, directly but not strongly related to an index of socioeconomic status, and was increased among women who gave a history of arthritis. Both fibrocystic disease and fibroadenoma were much less frequent in more obese women. Neither fibrocystic disease nor fibroadenoma has an epidemiologic pattern which corresponds closely to that of breast cancer. Therefore, it seems reasonable to suggest that the apparent increased risk of breast cancer among women with benign breast disease is concentrated within a subset of these women.

Adenofibroma↗
PubMed1985

Overweight and changes in weight throughout adult life in breast cancer etiology. A case-control study.

Numerous epidemiologic studies have found body size to be a significant risk factor in the etiology of breast cancer. In an Israeli study population of 1,065 breast cancer patients, 964 surgical controls, and 981 neighborhood controls, height and weight at three periods (age 18, "most of adult life," and recent) were ascertained. The authors analyzed these parameters and body mass index (weight/height) for each period, as well as body mass index changes throughout life, controlling for age, menstrual status, and ethnic origin. Odds ratios were determined for three body mass index categories: 19.1-23, 23.1-27, and 27.1+, with a relative risk of 1 for body mass index less than or equal to 19. Their results show an increase in risk for breast cancer with greater recent body mass index among postmenopausal women aged 60+ (n = 461 for breast cancer, n = 414 for surgical controls, n = 401 for neighborhood controls). Crude odds ratios for the breast cancer/surgical control comparison are 1.23, 1.58, and 2.20, respectively, for each body mass index category; for the breast cancer/neighborhood control comparison 2.16, 2.44, and 2.99, respectively. Odds ratios adjusted for confounding factors (ages at menarche, first birth, and menopause; number of births; years of education; previous benign breast disease; and family history of breast cancer) are 1.17, 1.44, and 2.38, respectively (breast cancer/surgical control); and 1.78, 1.92, and 2.53, respectively (breast cancer/neighborhood control). Overweight does not emerge as a risk factor for breast cancer among premenopausal or younger postmenopausal women. Weight loss from most of adult life to recent weight appears to be protective, since mean loss in the 60+ age category is greater in both control groups than in breast cancer patients. In addition, breast cancer patients aged 60+ gained more weight during adult life than controls, and premenopausal breast cancer patients gained less weight than controls (for both comparisons, p less than or equal to 0.05, breast cancer vs. all controls combined.

Adult↗
PubMed1986

Estrogen receptors in breast cancer. Association with epidemiologic risk factors.

This study examined the factors influencing estrogen receptor protein levels in a population-based group of 168 incident cases of breast cancer in Olmsted County, Minnesota. The medical histories of women with histologically confirmed breast cancer and measured estrogen receptor levels in the period from November 1977 through December 1982 were reviewed. Statistically significant positive univariate associations were found between tumor estrogen receptor protein level and age, postmenopausal status, nulliparity, late age at first birth, cholelithiasis and educational level. No association was found between tumor estrogen receptor level and other breast cancer risk factors. After adjustment for age, there was no association between the above factors and estrogen receptor protein level. On multivariate analysis, age remained a statistically significant predictor of a higher estrogen receptor protein level. These findings in a population-based group of women with breast cancer are similar to previous reports of hospital-based breast cancer patients.

Adult↗
PubMed1987

Epidemiologic determinants of the mammographic parenchymal pattern. A population-based study within a mammographic screening program.

Epidemiologic data and information on the mammographic parenchymal pattern (classified according to Wolfe (Cancer 1976;37:2486-92)) were obtained from 38,757 (89%) of all women who were invited to undergo mammography in a population-based screening program in Kopparberg County, Sweden, starting in October 1977. The prevalence of the high-risk patterns (P2 and DY) was significantly higher in women aged 46-50 years than in any younger or older age group. A univariate analysis revealed that the odds ratio (OR) of having a high-risk pattern increased regularly with increasing age at first birth and was highest in nulliparous women. These associations remained evident in all age groups and were most pronounced in the oldest women. A history of breast biopsy increased the likelihood of having a high-risk pattern (OR = 1.57), whereas a similar weak overall association with prior cancer in the contralateral breast (OR = 1.40) and with familiar occurrence of breast cancer (OR = 1.20) was eliminated when other confounding factors were considered in a multivariate analysis. The authors conclude that characteristics of the reproductive lives of women have a significant and lifelong impact on their mammographic parenchymal patterns.

Adult↗
PubMed1991

Polycystic ovaries and the risk of breast cancer.

Data from a case-control study that was conducted between 1980 and 1982 were analyzed to investigate the possible association between polycystic ovaries and the risk of breast cancer. The multicenter, population-based study included in-home interviews with 4,730 women with breast cancer and 4,688 control women aged 20-54 years. The age-adjusted odds ratio for breast cancer among women with a self-reported history of physician-diagnosed polycystic ovaries was 0.52 (95% confidence interval 0.32-0.87). The inverse association was not an artifact of infertility, age at first birth, or surgical menopause. Because women with this syndrome have abnormal levels of certain endogenous hormones, the observation of a low risk of breast cancer in this group may provide new insights into hormonal influences on breast cancer.

Adult↗
PubMed1995

Alcohol and breast cancer: results from The Netherlands Cohort Study.

Although the results of cohort studies on the association between alcohol and breast cancer are rather consistent, the current evidence is based solely on North American cohorts. Therefore, this association was evaluated in the Netherlands Cohort Study on diet and cancer, conducted since 1986 among 62,573 women aged 55-69 years. After 3.3 years of follow-up (1986-1989), 422 incident breast cancer cases for which there were complete alcohol consumption data were available for analysis. In multivariate case-cohort analyses, the rate ratio for breast cancer in drinkers versus nondrinkers was 1.31 (95 percent confidence interval 1.00-1.71). When separate alcohol intake categories were compared with nondrinking, the rate ratios were 1.30, 1.29, 1.28, and 1.72 for women who consumed < 5, 5-14, 15-29, and > or = 30 g of alcohol per day, respectively (trend p = 0.047). Whereas beer consumption was not associated with breast cancer risk, increased risks were found at higher levels of both wine and liquor consumption. The alcohol-breast cancer association was found to be stronger among women with a history of benign breast disease, women with a history of breast cancer among sister(s), and women with an early menopause, and it varied considerably according to age at first birth. These results support a positive association between alcohol and breast cancer among postmenopausal women. The increased risk was particularly found among women who consumed 30 g or more of alcohol daily.

Aged↗
PubMed1992

Sex hormones and cardiovascular risk.

Inspection of the age-incidence curve of ischaemic heart disease in both sexes shows an increase in slope for women around the menopause, approaching that of men at older ages. Although the increase is likely to be related to the menopause, epidemiological evidence is not defined. Likewise, there is some suggestion that reproductive factors may be related to the subsequent risk of cardiovascular diseases, since a few studies found an elevated risk in women with an earlier first birth. In terms of prevention and public health considerations, treatments via exogenous hormones are, however, much more important. A systematic overview of the available epidemiological evidence indicates that oestrogen replacement treatment is protective against ischaemic heart disease. The overall relative risks based on 18 studies and greater than 3300 cases was 0.81, with a narrow 95% confidence interval (0.76-0.85), thus suggesting a protective effect of 15-25%. This protection has a plausible biological interpretation in terms of increased high density lipoprotein (HDL) levels. The serum lipoprotein pattern can be unfavourably influenced by progestin supplementation. With reference to oral contraceptives, the relative risk for cardiovascular mortality was increased about twofold in current users. There appears now to be convincing evidence that the elevated risk is restricted to current users.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed2003

Characteristics of women with cosmetic breast implants compared with women with other types of cosmetic surgery and population-based controls in Denmark.

Herein the authors describe characteristics of women with breast implants compared with women with other types of cosmetic surgery as well as population controls. All women who acquired breast implants from 1977 to 1997 were identified from the files of two private plastic surgery clinics in Denmark. Patient characteristics were obtained through a self-administered questionnaire. The magnitude of differences between patient and control groups was estimated using odds ratios and 95% confidence intervals. Women with breast implants had a significantly lower body mass index and reported a two-fold greater incidence of current smoking compared with women from the general population and compared with women with other cosmetic surgery. Women with implants reported a greater number of full-term pregnancies and were less likely than controls to have had their first birth at age 30 years or older. Women with implants were not more likely than women in either control group to report a history of diseases, including connective tissue diseases, cancer, or depression before their implant surgery. Women with cosmetic breast implants differ from women with other forms of cosmetic surgery and from general population controls with respect to characteristics that may importantly influence health outcomes and that need to be addressed in future breast implant studies.

Adult↗
PubMed1991

A prospective study of reproductive history and exogenous estrogens on the risk of colorectal cancer in women.

Among 118,404 female registered nurses who responded to a mailed questionnaire and had no history of cancer in 1976, 191 colon cancers and 49 rectal cancers were diagnosed during 8 years of follow-up. We observed no material association between parity and colon cancer risk; women who bore four or more children had a risk similar to that of nulliparous women (age-adjusted RR = 1.1, 95% confidence limits (CL): 0.6, 1.9). No consistent patterns of colorectal cancer risk were associated with age at menarche or at first birth. Current or past use of oral contraceptives did not appreciably alter the risk of colorectal cancer; past use of postmenopausal estrogens was associated with a reduced risk of colorectal cancer (RR = 0.5, 95% CL: 0.3, 1.0). These and other data do not support any substantial effect of reproductive history or oral contraceptive use on the risk of large bowel cancer; however, the possible protective role of postmenopausal estrogen therapy merits further investigation.

Adult↗