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Biomedical subjects

L A Brinton

Publications and source records attributed to L A Brinton.

At least 19 recordsLinked to original sources

Geographic variation in mortality from breast cancer among white women in the United States.

BACKGROUND: For several decades, mortality from breast cancer has been higher in the northeastern part of the United States than in other regions, particularly the South. Rates have also been somewhat higher in the Midwest and West than in the South, especially among older women. The reasons for these geographic variations are not well understood. PURPOSE: The objective of this study was to evaluate geographic differences in U.S. breast cancer mortality rates in 1987, after taking into account regional differences in the distribution of recognized breast cancer risk factors (e.g., late age at first live birth) and certain prognostic factors (e.g., mammography use). METHODS: The 1987 breast cancer mortality rates for four regions of the country were obtained from the National Center for Health Statistics. Regional data on the distribution of breast cancer risk factors were obtained from 1987 National Health Interview Cancer Epidemiology Supplement interviews with 9778 white women aged 20-79 years. Regional data on the distribution of mammography use were obtained from 1987 National Health Interview Cancer Control Supplement interviews with 3795 white women aged 50-79 years. RESULTS: Age-adjusted mortality ratios (MRs) among women 50 years and older were 1.15, 1.18, and 1.30 in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among women 20-49 years old were 1.01, 1.08, and 1.07 in the West, Midwest, and Northeast, respectively, compared with the South. After adjustment for recognized risk factors and certain prognostic factors, MRs among older women were 1.13 (95% confidence interval [CI] = 1.04-1.23), 1.08 (95% CI = 1.01-1.16), and 1.13 (95% CI = 1.04-1.23) in the West, Midwest, and Northeast, respectively, compared with the South. Corresponding MRs among younger women were 0.94 (95% CI = 0.76-1.16), 1.05 (95% CI = 0.92-1.18), and 0.99 (95% CI = 0.86-1.14), respectively. CONCLUSION: Before adjustment for regional differences in recognized risk factors and prognostic factors, mortality excesses among younger women in the Northeast, Midwest, and West were less than 10% compared with the South. After adjustment, MRs were near unity for all regions. Among older women, the excess mortality was more substantial before adjustment for relevant factors, ranging from 15% in the West to 30% in the Northeast. Approximately 50% of the excesses in the Northeast and Midwest and 10% of the excess in the West could be explained on the basis of regional differences in the prevalence of recognized breast cancer risk factors and prognostic factors. After adjustment for these factors, the magnitude of excess in breast cancer mortality in the Northeast (13%) was comparable to that in the West (13%) but still slightly higher than that in the Midwest (8%).

Adult

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

Breastfeeding and breast cancer risk.

A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women (1,211 cases, 1,120 random-digit-dialing controls), a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87 (95 percent confidence interval [CI] = 0.7-1.0). This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breastfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined (RR = 0.67, CI = 0.4-1.1 for an average period per child of 72 or more weeks). Women who began to breastfeed at a young age (< 22 years) experienced the greatest reduction in risk, but other timing parameters (e.g., interval since first or last breastfeeding) were not predictive of risk. Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited. Use of medications to stop breast milk was unrelated to risk (RR = 1.04). The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breastfed only for limited periods of time (average breastfeeding per child of 30 weeks). Further studies are needed to clarify the relationship of breastfeeding to breast cancer risk, and to determine possible etiologic mechanisms underlying any observed associations.

Adult

Epidemiologic follow-up studies of breast augmentation patients.

Although hundreds of thousands of women in this country have had augmentation mammaplasty, little is known about long-term effects. Clinical studies have documented a decreased ability to detect breast lesions in women with implants, leading to concerns regarding breast cancer risk. There is also anecdotal evidence that implants might have effects on a variety of immune conditions. More recently, concern over carcinogenic effects has heightened given findings that the polyurethane foam, used in a minority of implants to envelope silicone gel, contains chemicals linked to cancer in laboratory animals. Only a few epidemiologic studies on long-term effects have been published, and all have had methodologic limitations, including the possibility of inappropriate comparison rates, limited and/or incomplete follow-up, absence of information on patients characteristics, and lack of specific information on types of implanted material. Several case-control and cohort studies are currently underway which are attempting to overcome methodologic limitations of previous studies. Past descriptive and analytic studies are reviewed. In addition, ongoing follow-up efforts are discussed, with attention given to the methodologic adjuncts necessary for allowing valid assessments of long-term disease effects.

Adolescent

Evidence of a healthy estrogen user survivor effect.

We examined the relation between menopausal estrogen use and all-cause and cause-specific mortality in a cohort of over 49,000 women followed between 1979 and 1989 in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-Up Study. We found a lower all-cause mortality rate among women who took estrogens [rate ratio (RR) = 0.7; 95% confidence interval (CI) = 0.7-0.8], particularly current users (RR = 0.3; 95% CI = 0.2-0.4), than among women who never took them. Additional analyses, however, revealed that women who had recently stopped taking estrogens had a higher all-cause mortality rate than women who had never taken them (RR = 1.4; 95% CI = 1.2-1.7). Women who had recently stopped taking estrogens also had higher mortality rates from circulatory disease (RR = 1.3; 95% CI = 1.0-1.8) and cancer (RR = 1.6; 95% CI = 1.2-2.2) than women who never took them. The most likely explanation for these results is that women stop taking estrogens when they develop symptoms of serious illness. As a consequence of this "healthy estrogen user survivor effect," nonexperimental studies are susceptible to overestimating the benefits of menopausal estrogen use, particularly current use, on mortality.

Aged

Relation of obesity and body fat distribution to endometrial cancer in Shanghai, China.

In a case-control study involving 268 cases of endometrial cancer and an equal number of population controls, we assessed the relationship of risk to body weight and fat distribution, examining weight at various ages and current anthropometric measurements. Weight gain during later adulthood and resultant high body masses were important risk predictors, indicating that obesity is an important risk factor, even in an area where the prevalence of obesity and incidence of endometrial cancer are low. Certain fat distribution patterns were related to risk of endometrial cancer independent of general obesity. In particular, fat deposits on the trunk were associated with elevated risks, with the odds ratio for the highest versus lowest quartile of subscapular skinfolds remaining significant even after adjustment for body mass index (odds ratio = 2.9; 95% confidence interval, 1.1-7.3). Central versus peripheral obesity, as measured by the subscapular:triceps ratio, also was related to increased risk, although the association failed to remain significant after adjustment for body mass (highest to lowest quartile, odds ratio = 1.7). In contrast, upper body obesity, as assessed by the waist:thigh ratio, was unrelated to risk. These results support the need for future studies assessing the relationship of hormonal and other biological parameters of fat distribution to assist in identifying causal mechanisms for this tumor.

Adolescent

In situ and invasive vulvar cancer incidence trends (1973 to 1987).

OBJECTIVE: The objective of this study was to examine recent trends in the incidence of vulvar cancer. STUDY DESIGN: Cases of in situ and invasive squamous cell vulvar cancer were identified from nine Surveillance, Epidemiology, and End Results cancer registries. RESULTS: The incidence rate of in situ vulvar cancer nearly doubled between 1973 to 1976 and 1985 to 1987, whereas the rate of invasive squamous cell carcinoma remained relatively stable. CONCLUSIONS: Possible reasons for this discordance include the following: (1) Women affected by the "sexual revolution" are not yet old enough to have invasive vulvar carcinoma; (2) early diagnosis and treatment of in situ carcinoma have mitigated anticipated increases in invasive vulvar carcinoma incidence; (3) in situ and invasive carcinomas of the vulva have different etiologies, with the sexually transmitted human papillomavirus involved in the etiology of in situ carcinoma and other factors involved with most invasive squamous cell carcinoma.

Adult

Supravaginal uterine amputation in Denmark 1978-1988 and risk of cancer.

In Denmark, total rather than subtotal hysterectomy has been recommended as treatment for benign conditions of the uterine corpus, primarily due to the risk of cervical cancer in the residual stump. Due to possible benefits during and after surgery, it has recently been argued that total hysterectomy for benign conditions could be substituted by subtotal hysterectomy, particularly since cancers of the cervix are declining as a consequence of screening. Cancer risk following supravaginal uterine amputation among 1104 Danish women undergoing operations during 1978-1988 was studied using record linkage techniques with the Danish Cancer Registry. No overall cancer risk, nor an overall increased risk of cancers coded as cervical, was observed. However, a 3.3 to 5.0-fold increased risk for cervical cancer was observed among women whose operations occurred at 50 years of age or older, possibly reflecting an increased risk of cancer in the endocervical area or in remaining uterine tissue. This observation, together with the difficulties in treating a cervical cancer of the stump when it does occur, should be taken into account before a change in surgical procedures from total to subtotal hysterectomies is recommended.

Adult

Height and weight at various ages and risk of breast cancer.

A study of 1529 breast cancer patients and 1901 control subjects enabled evaluation of risk in relation to lifetime changes in body size. Tallness, regardless of when achieved, was associated with an increased risk of breast cancer diagnosed at both young (< 50 years) and older ages, with adult height of 68 in or more increasing risk by nearly 50 to 80% compared with statures of less than 62 in. The association of risk with weight was less clear. Subjects who described themselves as heavier than average at ages 8 to 9 or 16 years were at reduced risk, particularly for older-onset breast cancer. Higher body mass indices based on reported weights during early adulthood were also associated with reduced risk. Measures of body mass beyond the age of 20, however, were less strongly related to risk. These inconsistent patterns appeared to be explained by an effect on risk of weight gain later in life, which was related to reduced risks for young-onset breast cancer and increased risks for later disease. The effect of weight change for early-onset breast cancer was not restricted to in situ cancers and could therefore not be attributed to detection bias. The direct relationship of body mass change with older onset disease was restricted to invasive cancers, consistent with observations of poor breast cancer prognosis among obese women. Further attention on the relationship of anthropometric variables to risk of breast cancer should focus on the timing of weight gain as well as the distribution of body fat.

Adolescent

Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case-control study.

OBJECTIVE: Our objective was to evaluate the risk for endometrial cancer in relation to reproductive, menstrual, and medical factors. STUDY DESIGN: A case-control study of 405 endometrial cancer cases and 297 population controls in five areas of the United States enabled risk to be evaluated. RESULTS: A major risk factor was the absence of a prior pregnancy (relative risk 2.8, 95% confidence interval 1.7 to 4.6). The protective effect of pregnancy appeared to reflect the influence of term births, because spontaneous and induced abortions were unrelated to risk. Among nulliparous women infertility was a significant risk factor, with women having sought medical advice having nearly eight times the risk of those without difficulty conceiving. After adjustment for other reproductive characteristics, age at first birth and duration of breast-feeding were not related to risk. CONCLUSIONS: Elevated risks were found for subjects reporting early ages at menarche (relative risk 2.4 for ages < 12 vs > or = 15) and longer days of flow (relative risk 1.9 for > or = 7 vs < 4 days), but there was no relationship with late ages at natural menopause. Height was not associated with risk, but there was a significant relation to weight, with the risk for 200 versus < 125 pounds being 7.2 (95% confidence interval 3.9 to 13.3). After adjustment for weight and other factors, histories of hypertension and gallbladder disease were not significantly related to risk, but an effect of diabetes persisted (relative risk 2.0, 95% confidence interval 1.1 to 3.6). Hirsutism developing at older ages was also significantly related (relative risk 2.0, 95% confidence interval 1.2 to 3.4).

Adult

Risk factors for epithelial ovarian cancer in Beijing, China.

A study in Beijing, China of 112 pathologically confirmed epithelial ovarian cancer cases and 224 age-matched community controls enabled evaluation of risk in relation to reproductive, medical, familial, and selected lifestyle factors. An inverse relationship was observed between the number of full-term pregnancies and ovarian cancer risk. Compared to nulliparous women, subjects with one, two, or three full-term pregnancies were at 50%, 70%, or 90% reduced risks, respectively (P for trend less than 0.01). A positive correlation was found between the number of ovulatory years and risk, with a 2.6-fold increased risk for women with 30 or more compared to less than 10 ovulatory years (P for trend less than 0.01). Infertility, as estimated in various ways, was also found to be an important risk factor. When parity was taken into account, age at first pregnancy was not related to ovarian cancer risk. No protective effect was associated with mumps virus infection. In contrast, risk increased significantly as serum mumps virus antibody titres increased (P for trend less than 0.01). An elevated risk was found in women with a history of long-term (greater than 3 months) application of talc-containing dusting powder to the lower abdomen and perineum (Relative risk 3.9, 95% confidence interval: 0.9-10.63). These findings suggest that Chinese women have risk factors similar to those of occidental women.

Carcinoma

Screening for cervical cancer in Latin America: a case-control study.

The beneficial effect of cervical cytology in reducing the incidence of invasive cervical cancer is well accepted, but many issues regarding specific patterns of screening remain to be resolved, and preventive programmes need to be adapted to regional characteristics. In a case-control study conducted in Latin America, we investigated cytological screening histories of 759 cases of invasive cervical cancer and 1430 controls, with participation rates of 99% and 96%, respectively. Fifty per cent of the cases and 29% of the controls reported never having been screened. Screening was less common among older, less educated and less parous women; non-users of oral contraceptives and women without histories of venereal diseases. There was also evidence that older women and those with multiple partners had longer intervals between examinations. The relative risk (RR) associated with no prior screening was approximately 3 and was not modified by other risk factors. Women reporting a Pap smear within 24-47 months before interview had the same RR as those examined within 12-23 months. Women tested longer ago had higher risks, but still much lower than women never examined. There was evidence that one examination is associated with less reduction in risk than two, regardless of the interval since last Pap smear. Screening appeared to reduce risk of both squamous cell carcinomas and adenocarcinomas. As expected, cases presenting at advanced stages were less likely to have been screened and reported longer intervals since their last examination. These results support the need to concentrate limited resources in the groups that need screening most, mainly older and less educated women who have never been screened.

Adult

Epidemiology of cervical cancer--overview.

Numerous studies of the epidemiology of cervical cancer have shown strong associations with religious, marital and sexual patterns. Although it is well established that women with multiple partners and early ages at first intercourse are at high risk, less is known about how these factors interact or how risk is affected by specific sexual characteristics. Recent studies indicate that number of steady partners and frequent intercourse at early ages may further enhance risk, supporting hypotheses regarding a vulnerable period of the cervix and a need for repeated exposure to an infectious agent. It is now widely accepted that HPV is the major infectious etiological agent, but whether other infectious agents play supportive or interactive roles is unclear. Of specific interest is the independent effect of HSV 2 on risk, especially given some evidence that this viral agent may interact with HPV. Other speculative risk factors for cervical cancer include cigarette smoking, oral contraceptive usage and certain nutritional deficiencies, but again it is not clear whether these factors operate independently from HPV. Although cervical cancer incidence trends correlate with the population prevalence of various venereally transmitted agents, it is not certain how disease rates are affected by other potential risk factors which have changed during recent time (e.g., exposure to HPV, sexual behaviour, cigarette smoking). In addition, a number of recent studies highlight the need for considering not only female influences on risk of cervical cancer, but also male factors, since the sexual behaviour of the male consort appears to play an important role.

Europe

A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators.

A study of 748 cases and 1,411 hospital and community controls in four Latin American countries evaluated the association between certain elements of diet and invasive cervical cancer. Subjects were interviewed about their adult consumption of 58 food items, including the major sources of putative protective agents (vitamin A, carotenoids, vitamin C, and folacin) as well as other behavioral and medical characteristics related to cervical cancer. Participation rates were above 95% for both cases and controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, and detection of human papillomavirus 16/18 by filter in situ hybridization, a slightly lower risk was observed for the highest quartiles of consumption of fruit and fruit juices, while no reductions in risk were associated with vegetables, foods of animal origin, complex carbohydrates, legumes, or folacin-rich foods. When nutrient indices were derived, significant trends of decreasing risk were observed for vitamin C (adjusted odds ratio (OR) = 0.69 for the highest vs. the lowest quartile; p for trend = 0.003), beta-carotene (OR = 0.68; p = 0.02), and other carotenoids (OR = 0.61; p = 0.003). Inclusion of vitamin C and beta-carotene in the same model attenuated the association with beta-carotene, while the association with vitamin C remained unchanged. The results are consistent with those of other investigations and provide support for a protective effect of vitamin C, carotenoids, and other substances found in the same fruits and vegetables against the development of invasive cervical cancer. However, the fact that the associations were driven by relation in two of the study sites and among women of higher socioeconomic status leaves open the possibility of selection bias or effects of unidentified aspects of dietary patterns.

Ascorbic Acid

A case-control study of nutrient status and invasive cervical cancer. II. Serologic indicators.

A study of 387 cases and 670 controls from four Latin American countries evaluated the hypothesis that lower serum levels of eight micronutrients were associated with a higher risk of invasive cervical cancer. The serologic analyses were restricted to a sample of subjects with stage I and II disease to minimize effects of the disease on the serologic markers. Ninety-four percent of eligible subjects donated blood samples, which were analyzed for carotenoids, retinol, and tocopherols by high-pressure liquid chromatography. Cases did not differ significantly from controls in mean serum levels of retinol, cryptoxanthin, lycopene, alpha-carotene, lutein, or alpha-tocopherol. The mean level of beta-carotene was lower and the mean level of gamma-tocopherol was higher among cases as compared with controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, detection of human papillomavirus types 16/18, cholesterol, and triglycerides, a trend of decreasing risk was associated with higher levels of beta-carotene (p for trend = 0.05), with the adjusted odds ratio decreasing to 0.72 for the highest versus the lowest quartile. beta-Carotene results were similar by stage of disease, which argues against an effect of disease progression on nutrient values. Unexpectedly, increasing risks were observed as the level of gamma-tocopherol increased (odds ratio = 2.09; p for trend = 0.03); however, levels were higher among stage II cases as compared with stage I cases, suggesting a metabolic alteration resulting from the disease process. The concordance in the strength and direction of the blood and dietary results, presented in the accompanying report (Herrero R, Potischman N, Brinton LA, et al., American Journal of Epidemiology 1991;134:1335-46), supports a role for beta-carotene or foods rich in beta-carotene in the etiology of cervical cancer. This study also indicates that simultaneous analysis using serologic and dietary nutrient indicators allows better discrimination of the association.

Carcinoma, Squamous Cell

Herpes simplex virus type 2: a possible interaction with human papillomavirus types 16/18 in the development of invasive cervical cancer.

A case-control study of 766 histologically confirmed incident cases of invasive cervical cancer and 1,532 hospital and community controls was conducted in Latin America to evaluate the etiologic role of herpes simplex virus type 2 (HSV-2) and to examine whether HSV-2 interacts with other risk factors. In addition to a personal interview, all subjects were asked to donate blood samples and cervical swabs for assessment of exposure to HSV-2 and human papillomaviruses (HPVs) respectively. Ninety-eight percent of cases and 91% of controls agreed to the interview and blood collection. Women testing positive for HSV-2 antibodies were found to have a 60% increased risk of cervical cancer compared with seronegative women (95% CI = 1.3, 1.9). Control for education, sexual and reproductive behavior, prior Pap-smear screening, smoking, oral contraceptive use, HPV-6/11 DNA, or HPV-16/18 DNA detection did not materially affect this estimate. No effect modification of HSV-2 by age, HPV-6/11 DNA, pregnancies, oral contraceptive use or cigarette smoking was observed. However, a significant interaction was detected between HSV-2 and HPV-16/18. Compared with women testing negative to both virus types, those positive for HSV-2 alone had a RR of 1.2 (95% CI = 0.9, 1.6), those positive for HPV-16/18 DNA alone had a RR of 4.3 (95% CI = 3.0, 6.0), and those positive for both viruses had a RR of 8.8 (95% CI = 5.9, 13.0). These findings corroborate recent laboratory evidence of a possible biological interaction between HSV-2 and HPV-16/18 in the development of cervical cancer. Further confirmatory studies are needed, given concerns with potential misclassification of exposure by the laboratory assays utilized.

Adult