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We examined the use of antibiotics among 2728 women with a first diagnosis of breast cancer during 1994-2003, and 27 280 population controls in North Jutland County, Denmark, based on hospital discharge diagnoses, prescription use from 1989 to 2002, and population registry data. We found no increased relative risk of breast cancer associated with use compared with nonuse. The odds ratio for breast cancer associated with more than 10 prescriptions for antibiotics was 1.00 (95% CI 0.86 -1.15). Relative risks were similar for different classes of antibiotics. A subanalysis based on cases and controls younger than 70 years of age, with data on first birth and number of children, showed similar risk estimates even after adjustment for age at first birth and parity. In our study, use of antibiotics was not associated with an increased risk of breast cancer.

Objective: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries)., Methods: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data., Results: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4)., Conclusions: Androgen-related phenomena are likely to be important in the etiology of breast cancer.

Previous research has demonstrated inconsistent associations between electromagnetic radiation, especially from electric blanket use, and breast cancer. Breast cancer risk according to electric blanket or mattress cover use was examined as part of a multicenter population-based case-control study. Breast cancer patients 50-79 years of age (N = 1949) were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from the period June 1994 to July 1995. Women of similar age were randomly selected from population lists as controls. Information regarding electric blanket and mattress cover use and breast cancer risk factors was obtained through telephone interviews. After adjustment for age, body mass index, and other breast cancer risk factors, the risk of breast cancer was similar among ever-users (relative risk = 0.93; 95% confidence interval = 0.82-1.06) and lower among current users than among never-users (relative risk = 0.79; 95% confidence interval = 0.66-0.95). There was no evidence of a dose-response relation with increasing number of months that electric blankets had been used. This study provides evidence against a positive association between electric blanket or mattress cover use and breast cancer.

Fractures in postmenopausal women may serve as a surrogate measure of bone density, reflecting long-term lower estrogen levels, and lower estrogen levels appear to be inversely associated with breast and endometrial cancer. Breast cancer cases aged 50-79 years (n = 5,559) and endometrial cancer cases aged 40-79 years (n = 739) were enrolled in a US case-control study in 1992-1994 to evaluate the relation between fractures and risk of breast and endometrial cancer. Controls for the breast cancer analysis (n = 5,829) and the endometrial cancer analysis (n = 2,334) were randomly selected from population lists (driver's license and Medicare files). Information on fracture history and other risk factors was obtained by telephone interview. Compared with women without a fracture in the past 5 years, the odds ratios for women with a history of fracture were 0.80 (95% confidence interval (CI): 0.68, 0.94) for breast cancer and 0.59 (95% CI: 0.40, 0.89) for endometrial cancer. Height loss (> or =2.5 cm) and recent fracture history were associated with the lowest risk of breast cancer (odds ratio = 0.62, 95% CI: 0.46, 0.83) and endometrial cancer (odds ratio = 0.15, 95% CI: 0.05, 0.43). These data suggest that the endogenous hormonal factors associated with increased fracture risk are also related to decreased breast cancer risk and, more strongly, to endometrial cancer risk.

Objective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case-control study of postmenopausal breast cancer., Methods: Participants included women aged 50 79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from driver's license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI)., Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (<45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84 0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95 1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06-1. 11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk., Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.

Breast cancer risk may be influenced by intrauterine exposure to steroid hormones. We evaluated left-handedness, a marker of intrauterine hormone exposure, in relation to breast cancer risk in our population-based, case-control study. Case women 50-79 years of age with a first diagnosis of invasive breast cancer were ascertained through statewide cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control women were identified in each state through lists of licensed drivers (for ages 50-64) and Medicare beneficiaries (for ages 65-79), and selected at random to correspond with the age distribution of case women. Exposure information, including handedness, was obtained through a telephone interview. Our results indicated a modest association between left-handedness and breast cancer risk (OR = 1.42; 95% CI = 1.10-1.83). The effect of left-handedness was modified by age; we observed the greatest risk ratio in the oldest age group. Left-handedness was not associated with breast tumor laterality. Our results are consistent with the hypothesis that intrauterine hormone exposures play a role in the development of breast cancer.

A modest inverse association between lactation and breast cancer risk has most consistently been observed in premenopausal women, and certain breastfeeding patterns, such as prolonged duration and early age at first lactation, may be important determinants of risk. However, these associations have not generally been observed in relation to postmenopausal breast cancer. As part of a multicenter population-based case-control study, the authors examined postmenopausal breast cancer risk according to breastfeeding characteristics. Breast cancer patients aged 50-79 years were identified from statewide tumor registries in Massachusetts, New Hampshire, and Wisconsin from July 1992 through July 1995. Similarly aged control women were randomly selected from population lists. Information regarding lactation history and breast cancer risk factors was obtained through telephone interviews. This analysis included only data on parous postmenopausal women (3,633 cases and 3,790 controls). After adjustment for age, parity, age at first birth, and other breast cancer risk factors, breastfeeding for at least 2 weeks was associated with a slightly reduced risk of breast cancer in comparison with women who had never lactated (relative risk = 0.87, 95% confidence interval 0.78-0.96). There was only a modest suggestion that increasing cumulative duration of lactation was inversely associated with breast cancer risk; the relative risk for women who had breastfed for > or =24 months was 0.73 (95% confidence interval 0.56-0.94) (p-trend for duration = 0.10). Age at first lactation was not consistently associated with risk. Modest inverse associations appeared to persist even up to 50 years since first lactation. Use of hormones to suppress lactation was not associated with postmenopausal breast cancer, nor was inability to breastfeed related to risk. These results suggest that lactation may have a slight and perhaps long-lasting protective effect on postmenopausal breast cancer risk.

While use of hormone-replacement therapy (HRT) effectively alleviates menopausal symptoms and prevents osteoporosis and possibly cardiovascular disease, there is concern of a detrimental impact on breast-cancer risk. There is a particular lack of data regarding the effect of long-term use of oestrogen-progestin combinations on breast-cancer risk. We conducted a large epidemiological study in Sweden, where combined oestrogen-progestin treatment has been predominant, to examine the influence of different regimens of menopausal hormone therapy on breast-cancer risk. In this population-based case-control study, 3,345 women aged 50 to 74 years with invasive breast cancer (84% of all eligible) and 3,454 controls of similar age (82% of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on use of hormone replacement and on potential confounding factors. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multiple logistic regression. There was a trend of increasing breast-cancer risk with duration of oestrogen/oestrogen-progestin use (OR for women treated at least 10 years, 2.43; 95% CI, 1.79-3.30, as compared to never-users), with statistically significant estimates only for women with BMI<27 kg/m2. Excess risks were observed to current use and use that ceased more than 10 years ago (OR for women treated at least 5 years, OR was 2.68, 95% CI, 2.09-3.42, and OR 2.57, 95% CI, 1.28-5.15, as compared with never-users, respectively). A positive association which was noted for use of oestrogen combined with testosterone-derived progestins appeared especially pronounced with continuously combined regimens. Long-term use of replacement oestrogens with or without progestins may substantially increase the incidence of post-menopausal breast cancer, particularly among non-obese women.

Objective: Breast size has been hypothesized to predict a woman's risk of breast cancer although studies in the main have not supported an association. In a large, population-based case-control study we examined whether breast size might emerge as a significant risk factor among very lean women in whom breast size might be a truer reflection of the volume of gland mass at risk for malignant change., Methods: The data derive from a population-based case-control study of women aged 50 to 79 years conducted in several New England states and Wisconsin. Incident cases of invasive breast cancer (n = 2015) were identified through state tumor registries and controls (n = 2556) were selected at random within age strata from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors which included bra dimensions (cup and back size) prior to a first birth, or at the age of 20 for nulliparous women., Results: We observed a significant positive association for cup size which was limited to women who were the most lean as young adults based on chest circumference. Among those reporting a chest size under 34 inches multivariate-adjusted relative risks were 1.34 (95% CI: 1.04 to 1.74) for cup size B, and 1.76 (95% CI: 1.04 to 3.01) for cup size C and larger, compared to a cup size smaller than B, and the trend for increasing cup size was statistically significant (P = 0.005). There was no relation with breast size among women reporting an average or larger back circumference (34 inches or larger)., Conclusion: Breast size before a pregnancy is a positive predictor of postmenopausal breast cancer, but this association is limited to those who were especially lean as young women.

It is unclear whether age at menarche is causally involved in breast-cancer aetiology, or serves a correlate of other early-life exposures. Other aspects of reproductive life, including cycle length and regularity, climacteric symptoms, reproductive history and oral contraceptive use, are also incompletely investigated. We examined these issues in a population-based case-control study, including 3,016 women aged 50 to 74 years with invasive breast cancer, and 3,263 controls of similar age. Mailed questionnaires and telephone interviews were used to collect information on menstrual and reproductive characteristics as well as use of oral contraceptives. We found a statistically significant negative association between increasing age at menarche and breast-cancer risk in women born before 1925 but not after. Length of the menstrual cycle at age 30 seemed to be adversely related to breast-cancer risk, with OR for women with cycle lengths < 24 days and > 30 days being 0.76 and 1.18, as compared with women with a cycle length of 28 days. There was a strong trend of decreasing breast-cancer risk with increasing parity (OR per borne child 0.85, 95% CI 0.80-0.90). Lactation, menopausal symptoms or past use of oral contraceptives did not appear associated with breast-cancer risk. Our findings provide some evidence of a role of environmental correlates of early menarche in breast-cancer aetiology, and underline the importance of childbirth, especially early in life, in the prevention of breast cancer. Our data are not readily compatible with an important influence of former oral contraceptive use on post-menopausal breast-cancer risk.

Background: There is considerable interest in the possibility of an infectious etiology for human breast cancer. Although studies have shown that certain strains of mice transmit mammary tumor virus via breast milk, few epidemiologic studies have addressed this topic in humans., Methods: We evaluated the relationship between having been breast-fed as an infant and breast cancer risk among 8299 women who participated in a population-based, case-control study of breast cancer in women aged 50 years or more. Case women were identified through cancer registries in three states (Massachusetts, New Hampshire, and Wisconsin); control women were identified through statewide driver's license lists (age <65 years) or Medicare lists (ages 65-79 years). Information on epidemiologic risk factors was obtained through telephone interview. We used multiple logistic regression to assess having been breast-fed and maternal history of breast cancer in relation to breast cancer occurrence both in premenopausal women (205 case women; 220 control women) and in postmenopausal women (3803 case women; 4071 control women)., Results: We found no evidence that having been breast-fed increased breast cancer risk in either premenopausal women (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.41-1.04) or postmenopausal women (OR = 0.95; 95% CI = 0.85-1.07). In addition, breast cancer risk was not increased by having been breast-fed by a mother who later developed breast cancer., Conclusion: Our results do not support the hypothesis that a transmissible agent in breast milk increases breast cancer risk. Because premenopausal women were not well represented in our study population, our findings with regard to this group may not be generalizable and should be viewed with caution.

We have used data from a large population-based case-control study in the United States to evaluate the effect of occupational physical activity on breast cancer risk. Women diagnosed with breast cancer identified from four state cancer registries, and controls randomly selected from lists of licensed drivers or Medicare beneficiaries, were interviewed by telephone for information on usual occupation and other factors. We classified usual occupation into one of four categories of physical activity. After excluding subjects for whom a strength rating could not be assigned, we had a final sample size of 4,863 cases and 6,783 controls. Using conditional logistic regression models, we calculated adjusted odds ratios (OR) and 95 percent confidence intervals (CI) for occupations having light, medium, and heavy activity compared with sedentary ones. Women with heavy-activity occupations had a lower risk of breast cancer than women with sedentary jobs (OR = 0.82, CI = 0.63-1.08), as did women with jobs with medium activity (OR = 0.86, CI = 0.77-0.97) or light activity (OR = 0.92, CI = 0.84-1.01). There was a significant decreasing trend in the ORs from sedentary to heavy work (P = 0.007). Although limited by exposure misclassification, these data are consistent with the hypothesis that physical activity reduces the risk of breast cancer.

Data from a population-based case control study were used to estimate occupation-specific relative risks for female breast cancer, adjusted for established breast cancer risk factors. Breast cancer cases under age 75 were identified from tumor registries in four states. Controls were randomly selected from driver's license and Medicare beneficiary lists. Information on usual occupation and risk factors was obtained by telephone interview. Odds ratios from logistic regression adjusted for age, state, body mass index, benign breast disease, family history of breast cancer, menopausal status, age at menarche, parity, age of first birth, lactation history, education, and alcohol consumption were calculated for each of 26 occupational groups. Complete occupational information was obtained for 6,835 cases and 9,453 controls. Of 26 occupational groups, only "administrative support occupations" had a statistically significantly increased risk of breast cancer (OR = 1.15, 95% CI 1.06-1.24). In these data, no specific occupational group had an unusual risk of breast cancer. Increased risks reported elsewhere for nurses and teachers were not corroborated.

We used data from a large population-based case-control study to test the hypothesis that women whose "usual occupation" entailed exposure to higher than background 60-Hz magnetic fields had a higher risk of breast cancer than women without such exposure. Breast cancer cases were identified from four statewide tumor registries, and controls were randomly selected from lists of licensed drivers and Medicare beneficiaries. Information on usual occupation and breast cancer risk factors was obtained by telephone interview. We calculated adjusted odds ratios from logistic regression models for women holding occupations with potential for low, medium, or high magnetic field exposure, compared with background exposure. There was a modest increase in risk for women with potential for high exposure [odds ratio (OR) = 1.43; 95% confidence interval (CI) = 0.99-2.09], and no increase for women with potential for medium (OR = 1.09; 95% CI = 0.83-1.42) or low (OR = 1.02; 95% CI = 0.91-1.15) exposure The risk among premenopausal women in the highest-exposure category was higher (OR = 1.98; 95% CI = 1.04-3.78) than for postmenopausal women (OR = 1.33; 95% CI = 0.82-2.17).

Background: The excess risk of breast cancer among Jewish women has been attributed to the effects of difference in lifestyle and reproductive patterns, but there is now evidence that Jewish women may be more likely than other women to inherit mutations in breast-cancer genes. We investigated whether any excessive risk among Jewish women is confined to those with a family history of breast cancer., Methods: We assessed the effect of Jewish religion on breast cancer in a large population-based case-control study (6611 women with breast cancer and 9026 controls) in USA. Participants were given telephone interviews and asked about known and suspected risk factors for breast cancer., Findings: Overall, Jewish women had only a slightly raised relative risk of breast cancer (1.10 [95% CI 0.84-1.44]; p=0.49). However, the relative risk was much higher for Jewish women with a first-degree relative who had breast cancer (3.78 [1.74-8.16]; p<0.001). The effect of family history was greater in Jewish women than in women of other religions (p interaction = 0.05)., Interpretation: These results are consistent with data suggesting that certain groups of Jewish women have a higher than expected rate of mutation in the breast-cancer gene BRCA1.

A priori hypotheses suggest that cigarette smoking could either increase or decrease breast cancer incidence. To clarify these competing hypotheses, we used data from a very large population-based breast cancer case-control study to investigate the impact of smoking on breast cancer risk. Breast cancer patients less than 75 years old were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly selected from driver's license lists (age less than 65) or lists of Medicare beneficiaries (age 65-74). Information on reproductive history, medical history, and personal habits including cigarette smoking was obtained by telephone interview. A total of 6,888 cases and 9,529 controls were interviewed. There was virtually no relationship between current smoking and breast cancer risk (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). Similar results were observed among both premenopausal and postmenopausal women. There was no suggestion that heavy or long-term smoking increased or decreased risk, nor were there indications that women who began smoking at an early age were at increased risk, as has been hypothesized. The results of this large population-based study indicate that smoking does not influence the risk of breast cancer, even among heavy smokers who began smoking at an early age.

Research regarding the relationship between alcohol intake and breast cancer risk has suggested an association between the two, although the data are inconsistent regarding dose effects and susceptible populations. To clarify these issues, we investigated the association of breast cancer risk with alcohol intake at various ages in a population-based case-control study nested within a screening cohort in Sweden. Subjects were women 40-75 years old who participated in a screening program in central Sweden. Information about personal characteristics, diet, and alcohol intake was obtained by a questionnaire sent out at the invitation to the screening interview and at a supplementary interview conducted among a sample of women who did and did not develop breast cancer. Alcohol intake did not affect breast cancer risk among women under 50 years old. However, among those over 50 years of age, ever-drinking conferred a relative risk of 1.8 (95% confidence interval = 1.2-2.6). Current and former drinkers had similar increases in risk. No particular latent period of alcohol effect was identified, but drinking later in life to have a bigger effect than did drinking earlier in life.

This case-control study addressed the relationship between cigarette smoking and cancers of the breast (1,741 cases), endometrium (476 cases), uterine cervix (1,174 cases), and ovary (296 cases). The lifetime smoking history of cases was compared with that of 2,128 controls, and relative risks (odds ratios) for smoking were estimated using multiple logistic regression to adjust for potential confounding by age, marital status, number of pregnancies, and Quetelet's index. With increasing amount smoked there was a statistically significant decrease in endometrial cancer risk and a statistically significant increase in cervical cancer risk. In the highest smoking category (greater than or equal to 15 pack-yr), the endometrial cancer relative risk was 0.57 [95% confidence interval (CI) of 0.37, 0.86] and the cervical cancer relative risk was 1.81 (95% CI of 1.47, 2.22). There was no apparent relationship between smoking and cancers of the breast or ovary.

The relation between cigarette smoking and the risk of breast cancer in women was investigated in a population-based case-control study conducted in Adelaide, Australia during 1982-1984. Cases were identified through the South Australian Central Cancer Registry, and, for each case, one age-matched control was selected from the electoral register; in all, 451 case-control pairs were enrolled. Overall, no clear association was found between ever or current smoking and breast cancer risk. In a subgroup analysis, premenopausal ex-smokers were observed to have an increased risk (estimated odds ratio = 2.3). The absence of a protective effect of cigarette smoking on breast cancer risk may reflect the relatively weak estrogen dependence of breast cancer, or the nature of its hormone dependence.

Maternal age at time of birth was investigated as a risk factor for breast cancer in a study of 1,176 matched case-control pairs. There was no pattern of increasing adjusted relative risk of breast cancer with increasing maternal age, nor was the mean maternal age of cases older than that of controls. Similar negative results were found among the subset of subjects up to 35 years old, a group previously found to show marked maternal age effects. Thus previous reports of an association between breast cancer and advanced maternal age may have been due to chance, extraneous factors, or a misleading reliance on unadjusted mean maternal ages, rather than on relative risks.