Hormonal content and potency of oral contraceptives and breast cancer risk among young women.

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

Patterns and predictors of the breast cancer detection methods in women under 45 years of age (United States).

OBJECTIVES: Few studies have examined methods by which breast cancers are detected, and only one study has been published on predictors of those methods. This study examined patterns and predictors of breast cancer detection methods during 1990-1992 among women age 20-44. METHODS: In-person interview and medical record data were obtained during a population-based case-control study of 1619 women newly diagnosed with breast cancer in three areas of the United States (US). RESULTS: Seventy-one percent of the cancers were identified by self-detection, 9% by routine clinical breast exam (CBE), and 20% by routine mammography. Cancers detected by mammography and CBE, but not those detected by breast self-exam, were much more likely to be early-stage. Detection by mammography increased with age, and a history of mammography use was associated with detection by mammography or CBE. Several commonly studied predictors of screening utilization in the US population were associated with CBE detection, but were less clearly related to or unrelated to mammography detection. CONCLUSION: Findings suggest that, during the 1990s in the US, most breast cancers among women under age 45, including those age 40-44, were self-detected. Few factors other than age and prior screening are verified predictors of method of breast cancer detection.

Ability of young women to recall past body size and age at menarche.

OBJECTIVE: The ability of young women (n = 132, average age 17 years) to recall body size and age at menarche was examined. The use of body silhouettes to assist women in recalling their body size at menarche and to represent their current body size was also evaluated. RESEARCH METHODS AND PROCEDURES: Subjects, who previously participated in a cohort study, were asked to recall height and weight at the time of menarche, to select body silhouettes that best reflected their body shape at the time of menarche and their current body shape, and to recall age at menarche. Two sets of body silhouettes were developed, one representative of an adult body shape and another representative of an adolescent body shape. RESULTS: Pearson correlation coefficients between the adult and adolescent body figures and actual body mass index (BMI; kg/m(2)) at the time of menarche were not significantly different (r = 0.82 for adult figures vs. r = 0.72 for adolescent figures, p > 0.05). The correlation between actual BMI at the time of menarche and body silhouette (r = 0.77, all subjects) was similar to the correlation between actual and recalled BMI at the time of menarche (r = 0.83) as well as the correlation between current BMI and current body silhouette (r = 0.75). Recalled and actual ages at menarche were highly correlated (r = 0.83). DISCUSSION: The recall of body shape was considered to be a less precise measure of body size than asking about height and weight, but use of body silhouettes may offer advantages in certain situations.

Comparison of telephone sampling and area sampling: response rates and within-household coverage.

Random digit dialing is used frequently in epidemiologic case-control studies to select population-based controls, even when both cases and controls are interviewed face-to-face. However, concerns persist about the potential biases of random digit dialing, particularly given its generally lower response rates. In an Atlanta, Georgia, case-control study of breast cancer among women aged 20-54 years, all of whom were interviewed face-to-face, two statistically independent control groups were compared: those obtained through random digit dialing (n = 652) and those obtained through area probability sampling (n = 640). The household screening rate was significantly higher for the area sample, by 5.5%. Interview response rates were comparable. The telephone sample estimated a significantly larger percentage (by approximately 7%) of households to have no age-eligible women. Both control groups, appropriately weighted, had characteristics similar to US Census demographic characteristics for Atlanta women, except that respondents in both control groups were more educated and more likely to be married. The authors conclude that households contacted through random digit dialing are somewhat less likely to participate in the household screening process, and if they are cooperative, some households may not disclose that age-eligible women reside therein. Investigators need to develop improved methods for screening and enumerating household members in random digit dialing surveys that target a specific subpopulation, such as women.

Case-control assessment of the association between non-Hodgkin's lymphoma and occupational radiation with doses assessed using a job exposure matrix.

BACKGROUND: Epidemiologic data for an association between radiation exposure and non-Hodgkin's lymphoma (NHL) have been inconclusive though the strongest evidence has been provided by studies of patients treated with radiotherapy. METHODS: We evaluated the association between occupational radiation exposure and non-Hodgkin's lymphoma in men using a population-based case-control study with 1,056 case and 1,860 control subjects sampled from eight geographic areas in the United States. Because dosimetry data were not available, doses were estimated for individuals who reported occupational radiation exposure using a radiation job exposure matrix developed for this purpose. Conditional logistic regression was used to model the association between reported occupational radiation exposure and NHL incidence. RESULTS: We found that most men (> 90%) did not report exposure to occupational sources of radiation. Among those who reported exposure, estimated cumulative doses were low, with an estimated mean of less than 0.02 Gray and a maximum of 0.12 Gray. The risk for NHL was not associated with ever having reported an occupational radiation exposure (OR = 0.90, 95% CI = 0.74-1.10) nor was there evidence of a dose-response relationship between risk and either the estimated cumulative doses or duration of exposure. CONCLUSIONS: The findings in this study are consistent with results from most current research on occupational radiation and NHL risk that have found no increased risk of NHL at low levels of occupational radiation exposure. While it should be noted that exposure misclassification likely biased our results toward the null, this large population-based case-control study adds to existing evidence which suggests that there is little to no increased risk for NHL associated with exposure to low levels of radiation such as that commonly found in many occupational settings.

Validation of the American Cancer Society Cancer Prevention Study II Nutrition Survey Cohort Food Frequency Questionnaire.

We assessed the validity and reproducibility of a self-administered 68-item food frequency questionnaire completed in 1992-1993 by approximately 185,000 adults. Four hundred forty-one participants completed four 24-hour dietary recall interviews over a 1-year period and a repeat administration of the food frequency questionnaire. For 20 nutrients and 10 food groups, measured nutrient intakes, but not food group intakes, were consistently lower by food frequency questionnaire than by recall. Energy-adjusted, attenuation-corrected Pearson validity correlations ranged from 0.12 to 0.80, with a median of 0.58. Reproducibility measures were generally high, with a median of 0.69. The food frequency questionnaire performed similarly to food frequency questionnaires used in other cohort studies, indicating similar ability to examine diet-disease relations.

Tubal ligation and risk of breast cancer.

Although it has been demonstrated in previous studies that tubal ligation can have widespread effects on ovarian function, including a decrease in the risk of subsequent ovarian cancer, few studies have evaluated effects on breast cancer risk. In a population-based case-control study of breast cancer among women 20-54 years of age conducted in three geographic areas, previous tubal ligations were reported by 25.3% of the 2173 cases and 25.8% of the 1990 controls. Initially it appeared that tubal ligations might impart a slight reduction in risk, particularly among women undergoing the procedure at young ages (<25 years). However, women were more likely to have had the procedure if they were black, less educated, young when they bore their first child, or multiparous. After accounting for these factors, tubal ligations were unrelated to breast cancer risk (relative risk (RR) = 1.09, 95% confidence interval (CI) 0.9-1.3), with no variation in risk by age at, interval since, or calendar year of the procedure. The relationship of tubal ligations to risk did not vary according to the presence of a number of other risk factors, including menopausal status or screening history. Furthermore, effects of tubal ligation were similar for all stages at breast cancer diagnosis. Further studies would be worthwhile given the biologic plausibility of an association. However, future investigations should include information on type of procedure performed (since this may relate to biologic effects) as well as other breast cancer risk factors.

Characteristics associated with recent recreational exercise among women 20 to 44 years of age.

Data on 1,501 control women from a multi-center, population-based, case-control study of breast cancer were used to examine characteristics associated with recreational exercise during the year prior to the interview among women 20 to 44 years of age. In a univariate analysis, higher levels of recreational exercise were associated with: higher education; higher family income; white race; previous participation in recreational exercise above the median level at ages 12 to 13 and at age 20; being nulliparous; ever lactating; being a never or past smoker; having a low current Quetelet's index (QI: weight in kilograms divided by height in meters squared); and living in Atlanta or Seattle (compared to New Jersey). In a multiple linear regression model, independent predictors of higher levels of recreational exercise were: participation in higher levels of exercise at 20 years of age; having a low current QI; and never having smoked. Though all women should be encouraged to participate in exercise, these findings identity subgroups of women that may need targeting when developing exercise intervention programs.

Breast cancer risk in young women and history of selected medical conditions.

BACKGROUND: Several common medical conditions are associated with altered hormone levels, and may thus plausibly influence breast cancer risk. Few studies have examined such relationships, and we utilized a population-based case-control study of young women in the US to examine breast cancer risk following a history of various medical conditions. Relationships between breast cancer and each medical condition examined are biologically plausible, and relevant in terms of public health. METHODS: The study included 2173 breast cancer cases and 1990 population-based controls from three areas of the US, under 55 years, who were administered a questionnaire including details of physician-diagnosed medical conditions. RESULTS: No significantly increased or decreased breast cancer risk was associated with a history of thyroid disease, gallbladder disease, colorectal polyps, diabetes, high blood pressure, high cholesterol or surgery for endometriosis. There was some evidence of an increased breast cancer risk associated with ovarian cysts among women who did not receive an oophorectomy (relative risk [RR] = 1.94, 95% CI: 1.0-3.9). Non-significant increases in breast cancer risk were observed following diagnoses of several other cancers, including thyroid cancer, basal cell carcinoma, Hodgkin's disease and malignant melanoma. CONCLUSIONS: To conclude, our generally null results from this large, population-based study support results from previous studies in providing reassurance that women with a history of several common medical conditions do not appear to be at an increased risk of breast cancer at a young age.

Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood.

Findings have been inconsistent on effects of adolescent body size and adult weight gain on risk of breast cancer in young women. These relations were examined in a population-based case control study of 1590 women less than 45 years of age newly diagnosed with breast cancer during 1990-1992 in three areas of the US and an age-matched control group of 1390 women. Height and weight were measured at interview and participants asked to recall information about earlier body size. Logistic regression was used to estimate the relative risk of breast cancer adjusted for other risk factors. Women who were either much heavier or lighter than average in adolescence or at age 20 were at reduced risk. Weight gain after age 20 resulted in reduced risk, but the effect was confined to early-stage and, more specifically, lower grade breast cancer. Neither the risk reduction nor the variation by breast cancer stage or grade was explained by the method of cancer detection or by prior mammography history. These findings suggest that relations between breast cancer risk in young women and body weight at different ages is complex and that the risk reduction with adult weight gain is confined to less aggressive cancers.

Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer.

Epidemiologic studies have evaluated the risk of breast cancer related to dietary fat intake, but only recently have other dietary factors received attention. Frequent intakes of fruit, vegetables and fiber have been associated with low risk of the disease in some studies but results are inconsistent. In a large case-control study of early-onset breast cancer, we evaluated risk related to a variety of food groups, associated micronutrients and non-nutritive constituents. Cases treated with chemotherapy appeared to have altered reporting of food intake and were excluded. Analyses were restricted to 568 cases with in situ and localized disease and 1,451 population-based controls. Reduced risks were observed for high intake of cereals and grains [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.6-1.1 for highest compared with lowest quartile], vegetables (OR = 0.86, 95% CI = 0.6-1.1), beans (OR = 0.87, 95% CI = 0.7-1.2) and fiber from beans (OR = 0.88, 95% CI = 0.7-1.2). However, no trends of decreasing risk across quartiles of increasing intake were observed. Risk was not associated with dietary constituents related to these food groups including dietary fiber, carotenoids, vitamins A, C and E and folate. Incorporation of information from vitamin supplements did not alter the results for micronutrients. Our data suggest that intakes of cereals and grains, vegetables and beans are associated with minimal, if any, reduction in risk of early-stage breast cancer among young women.

Stage of breast cancer in relation to body mass index and bra cup size.

Most studies on women with breast cancer indicate that obesity is positively associated with late-stage disease. Some results have shown a similar relationship between breast size and stage. A recent study found that the association between body mass index (BMI) and stage was limited to cancers that were self-detected, suggesting that the BMI-stage relation may be due to delayed symptom recognition. We examined the relationships between stage and both BMI and breast (bra cup) size, stratified by method of detection, using data from a population-based case-control study of 1,361 women (ages 20-44 years) diagnosed with breast cancer during 1990-1992. Height and weight measurements and information on bra cup size, method of cancer detection and other factors predictive of stage at diagnosis were collected during in-person interviews. A case-case comparison was conducted using logistic regression to estimate odds of regional or distant stage rather than local stage in relation to BMI and bra size. Odds of late-stage disease were increased with higher BMI [adjusted odds ratio (OR) for highest to lowest tertile = 1.46, 95% confidence interval (CI) 1.10-1.93] and larger bra cup size (OR for cup D vs. cup A = 1.61, 95% CI 1.04-2.48). These relationships were not modified by the method of detection. Differences in etiologic effects, rather than differences in detection methods, may explain the relations observed between stage and both BMI and breast size.

The Women's Health Trial Feasibility Study in Minority Populations: changes in dietary intakes.

This randomized clinical trial examined the feasibility of low-fat dietary interventions among postmenopausal women of diverse backgrounds. During 1992-1994, 2,208 women aged 50-79 years, 28% of whom were black and 16% Hispanic, enrolled at clinics in Atlanta, Georgia, Birmingham, Alabama, and Miami, Florida. Intervention/support groups met periodically with a nutritionist to reduce fat intake to 20% of energy and to make other diet modifications. At 6 months postrandomization, the intervention group reduced fat intake from 39.7% of energy at baseline to 26.4%, a reduction of 13.3% of energy, compared with 2.3% among controls. Saturated fatty acid and cholesterol intakes were reduced, but intakes of fruits and vegetables, but not grain products, increased. Similar effects were observed at 12 and 18 months. Black and non-Hispanic white women had similar levels of reduction in fat, but the decrease in Hispanic women was less. Changes did not vary significantly by education. While bias in self-reported intakes may have resulted in somewhat overestimated changes in fat intake, the reported reduction was similar to the approximately 10% of energy decrease found in most trials and suggests that large changes in fat consumption can be attained in diverse study populations and in many subgroups.

Pregnancy characteristics and maternal risk of breast cancer.

In a population-based case-control study of parous women less than 45 years of age, we evaluated the relations of various pregnancy characteristics to maternal breast cancer risk. Cases (N = 1,239) diagnosed with in situ or invasive breast cancer from 1990 to 1992 in Atlanta, GA, Seattle/Puget Sound, WA, and five counties in central New Jersey, and population controls (N = 1,166) identified by random-digit dialing, were interviewed regarding the details of their pregnancies. We used logistic regression to estimate relative risks (RR) and 95% confidence intervals (CI) and to adjust for breast cancer risk factors. Women who reported nausea or vomiting in their first pregnancy had a slightly lower risk of breast cancer (RR = 0.87; 95% CI = 0.72-1.0). We found no strong or consistent associations for maternal risk related to gestational length, pregnancy weight gain, gestational diabetes, pregnancy hypertension, or gender of the offspring, although we found some evidence for reductions in risk for toxemia (RR = 0.81; 95% CI = 0.61-1.1) and specific sex (RR for female twins vs singletons = 0.48; 95% CI = 0.20-1.3) and timing characteristics of twinning. Overall, these data provide little support for the hypothesis that pregnancy hormone levels are associated with subsequent maternal risk of breast cancer in young women.

Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy.

OBJECTIVE: To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. DESIGN: A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. RESULTS: Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. CONCLUSIONS: Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy.

Electric blanket use and breast cancer risk among younger women.

To investigate whether use of electric blankets, one of the largest sources of electromagnetic field exposure in the home, is associated with the risk of female breast cancer, the authors analyzed data from a population-based US case-control study. The 2,199 case patients were under age 55 years and had been newly diagnosed with breast cancer between 1990 and 1992. The 2,009 controls were frequency-matched to cases by 5-year age group and geographic area. There was little or no risk associated with ever having used electric blankets, mattress pads, or heated water beds among women under age 45 years (adjusted odds ratio = 1.01, 95% confidence interval 0.86-1.18) or among women aged > or =45 years (adjusted odds ratio = 1.12, 95% confidence interval 0.87-1.43). There was no substantial variation in risk with duration of use; with whether the appliance was used only to warm the bed or used throughout the night; with menopausal status; or with the cases' hormone receptor status or stage of disease. Potential breast cancer risk factors that were associated with electric blanket use did not substantially confound the associations under investigation. These data do not support the hypothesis that electric blanket use increases breast cancer risk among women under age 55 years.

Fertility problems and breast cancer risk in young women: a case-control study in the United States.

OBJECTIVES: Late age at first birth and nulliparity are established risk factors for breast cancer, yet the extent to which fertility problems contribute to these associations remains largely unexplored. Here, we examine self-reported fertility problems as a risk factor for breast cancer in young women. METHODS: We used a population-based case-control study of 2,173 cases and 1,990 controls aged 20 to 54 years in the United States. Structured in-person interviews were used to elicit detailed information on established and potential breast cancer risk factors. Information was collected on pregnancy details, including difficulties becoming pregnant or maintaining a pregnancy. RESULTS: Self-reported difficulty in becoming pregnant or maintaining a pregnancy was reported by 450 cases and 377 controls. Overall, there was little association between these fertility problems and risk of breast cancer (odds ratio [OR] = 1.05). Parity was associated with a decreased risk of breast cancer in women both with (OR = 0.71) and without (OR = 0.79) fertility problems. There was little evidence of an increased risk of breast cancer with later age at first full-term birth among women without fertility problems (ORage 35+ :age <20 = 1.13, 95 percent confidence interval [CI] = 0.7-1.9), but a relatively strong association among women with fertility problems (ORage 35+ :age <20 = 2.96, CI = 1.3-7.0). Among women with a first full-term birth at age 35 or older, fertility problems were associated with a twofold risk of breast cancer. Analyses of duration of unprotected sexual intercourse prior to first pregnancy as an alternative estimate of infertility produced similar results. CONCLUSIONS: Our study suggests that the association between late age at first birth and breast cancer is stronger among women with self-reported fertility problems than among women with no fertility problems.

Recreational physical activity and breast cancer risk among women under age 45 years.

To evaluate whether recreational physical activity is associated with breast cancer among young women, the authors analyzed data from a population-based case-control study. Cases (n = 1,668) were women under age 45 years who had been newly diagnosed with breast cancer between 1990 and 1992 in Atlanta, Georgia, central New Jersey, or Seattle, Washington. Controls (n = 1,505) were frequency-matched to cases by 5-year age group and geographic area of residence. Breast cancer was not associated with recreational activity in any of the three time periods assessed (highest quartile of activity vs. lowest: age- and center-adjusted odds ratio (OR) = 0.94 (95% confidence interval (CI) 0.77-1.15) at ages 12-13 years, OR = 1.08 (95% CI 0.88-1.32) at age 20 years, and OR = 1.18 (95% CI 0.97-1.44) during the past year), with the average of the three time periods (OR = 1.02, 95% CI 0.84-1.25), or with daily climbing of at least two flights of stairs (without stopping) during the past year (daily climbing vs. never climbing: OR = 1.03, 95% CI 0.86-1.23). Estimates were not modified or confounded by body mass index, menopausal status, or caloric intake during the past year. These results do not support a protective role for physical activity in the risk of breast cancer among young women.