Potential Breast Cancer Risk Factors Research Articles

Joint Effects of Febrile Acute Infection and an Interferon-γ Polymorphism on Breast Cancer Risk

BackgroundThere is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-γ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk.Methodology and Principal FindingsInformation on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-γ (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ≥1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61–0.99)] compared to those with less than one fever a year. This association only occurred in women with CT/TT genotypes [0.54 (0.37–0.77)] but not in those with the CC genotype [1.09 (0.77–1.55)]. The association of IFN-γ rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03–1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40–0.99)] among women with ≥1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-γ genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively).ConclusionsOur findings indicate a possible link between febrile acute infection and a decreased risk of breast cancer, and this association was modified by IFN-γ rs2069705.

Urinary strontium and the risk of breast cancer: A case-control study in Guangzhou, China

Strontium has been widely used in industries like electronic and pharmacy. It has a carcinogenic potential, however, and no study has been conducted to evaluate its effects on cancer risk. The aim of this study was to explore the possible association between strontium and breast cancer risk in a case-control study including 240 incident invasive breast cancer patients and 246 age-matched controls. We measured the urinary concentrations of strontium by inductively coupled plasma mass spectrometry, and conducted face-to-face interviews to obtain information on potential breast cancer risk factors. Multivariable analysis was used to estimate the association. Creatinine-adjusted levels [median (25th, 75th)μg/g] of strontium were 155.59 (99.05, 230.70) in the breast cancer patients and 119.62 (81.97, 163.76) in the controls. Women in the highest tertile of strontium showed 124% increased risk of breast cancer, when compared with those in the lowest tertile after adjustment for the potential risk factors [OR (95% CI): 2.24 (1.42–3.81)]. This association was particularly strong for HER2 positive breast cancer [OR (95% CI): 10.92 (3.53–33.77)], and only occurred among premenopausal women. These results suggest a potential role of strontium in the development of breast cancer and urge further studies on the environmental contamination and the physiological and pathological mechanisms of strontium.

Abstract B100: Index-based dietary patterns and risk of breast cancer in postmenopausal women in the NIH-AARP Diet and Health Study

Abstract Background: Because foods and nutrients could have synergistic or antagonistic effects when they are consumed in combination, dietary patterns in relation to diseases are a growing interest. Index-based dietary patterns that are created based on recommended dietary guidelines and Mediterranean Diet Score have been related to lower risk of some diseases. Objectives: We examined Healthy Eating Index 2005 (HEI), Alternative Healthy Eating Index (AHEI), and Alternative Mediterranean Diet Score (AMED) were associated with breast cancer risk. We also investigated the association by hormone receptor status of breast cancer. Methods: The NIH-AARP Diet and Health Study consisted of 184,932 postmenopausal women aged 50–71 years at baseline and followed them from 1995 to 2006. The scores for each dietary pattern was calculated based on intakes assessed by a 124-items food frequency questionnaire. Cancer cases were ascertained through state cancer registries. Thirty nine percent of breast cancer cases had information on hormone receptor status. Cox Proportional hazard model, with person-years as the underlying time metric, was used to estimate the relative risk (RR) and 95% confidence intervals (CI), adjusting for potential breast cancer risk factors. Results: During an average nine year follow up, 7,182 incident invasive breast cancer cases were identified. Both HEI and AHEI were inversely associated with risk of breast cancer. Compared with the lowest quintile of HEI, RR for the highest quintile was 0.91 (95% CI: 0.84–0.98 p-trend=0.01). RR for the highest quintile of AHEI vs. the lowest was 0.92 (95% CI: 0.85–1.00, p-trend=0.04). The AMED was also related to lower risk of breast cancer. Compared with women with low AMED score (0–3), women with high AMED score (7–9) had 10% lowered risk of breast cancer (RR: 0.90, 95% CI: 0.82–0.99, p-trend=0.01). Although it was not statistically significant, the association of index-based dietary patterns with risk of ER− was slightly stronger than those with ER+. RR for the highest quintile of HEI vs. the lowest was 0.70 (95% CI: 0.52–0.95, p-trend=0.12, n=459 cases) for ER− breast cancer and 0.95 (95% CI: 0.83–1.09, p-trend=0.30, n=2,322 cases) for ER+ breast cancer. In contrast, the highest AMED score vs. the lowest was 0.87 (95% CI: 0.73–1.03, p-trend=0.16) for ER+ and 0.91 (95% CI: 0.62–1.31, p-trend=0.26) for ER− cases. Conclusion: Dietary patterns based on Dietary Guidelines for Americans or Mediterranean diet were related to a lower risk of breast cancer in postmenopausal women. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B100.

Self-reported psychological stress and the risk of breast cancer: A case-control study

The aim of this study was to examine the relationship between severe life events and breast cancer risk. This study was based on a case–control examination of 858 Polish invasive breast cancer cases and 1085 controls matched for age and place of residence. Data on life events, sociodemographic characteristic, reproductive factors, family history of breast cancer, current weight and height, and lifestyle habits were collected between January 2003 and May 2007 using a self-administered questionnaire. Odds ratios with 95% confidence intervals were estimated as the measure of the relationship between life event stress and breast cancer risk using unconditional logistic regression analyses. After adjustment for potential breast cancer risk factors, women with four to six individual major life events had 5.33 times higher risk for breast cancer, compared with those in the lowest quartile. Similarly, women with a lifetime life change score greater than 210 had about 5 times higher risk compared to women with corresponding scores in the range 0–70. Several life events (death of a close family member, personal injury or illness, imprisonment/trouble with the law, retirement) were significantly associated with breast cancer risk. These findings suggest that major life events can play an important role in the etiology of breast cancer.

Does the Modern Urbanized Sleeping Habitat Pose a Breast Cancer Risk?

Due to its disruptive effects on circadian rhythms and sleep deprivation at night, shiftworking is currently recognized as a risk factor for breast cancer (BC). As revealed by the present analysis based on a comparative case-control study of 1679 women, exposure to light-at-night (LAN) in the “sleeping habitat” is significantly associated with BC risk (odds ratio [OR] = 1.220, 95% confidence interval [CI] = 1.118–1.311; p < .001), controlling for education, ethnicity, fertility, and alcohol consumption. The novelty of the present research is that, to the best of the authors' knowledge, it is the first study to have identified an unequivocal positive association between bedroom-light intensity and BC risk. Thus, according to the results of the present study, not only should artificial light exposure in the working environment be considered as a potential risk factor for BC, but also LAN in the “sleeping habitat.” (Author correspondence: ahaim@research.haifa.ac.il)

The first national public breast cancer screening program in Saudi Arabia

BACKGROUND AND OBJECTIVES:Despite its relatively low incidence in Saudi Arabia, breast cancer has been the most common cancer among Saudi females for the past 12 consecutive years. The objective of this study was to report the results of the first national public breast cancer screening program in Saudi Arabia.METHODS:Women 40 years of age or older underwent breast cancer screening. Mammograms were scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations between imaging findings, risk factors and pathological findings were analyzed.RESULTS:Between September 2007 and April 2008, 1215 women were enrolled. The median age was 45 years, and median body mass index was 31.6 kg/m2. Sixteen cases of cancer were diagnosed. No cancer was diagnosed in 942 women with R1/R2 scores, and only 1 case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions. No correlation was found between known risk factors and imaging score or cancer diagnosis.CONCLUSIONS:Public acceptance of the breast cancer screening program was encouraging. Longitudinal follow-up will help in better determining the risk factors relevant to our patient population.

Abstract B117: Association of endogenous sex hormone levels with breast cancer risk factors in premenopausal Japanese women

Abstract We assessed associations between blood levels of estrogen and androgen and breast cancer risk factors in premenopausal Japanese women. A total of 551 premenopausal women who reported having regular menstrual cycles less than 40 days long were included in the present study. Women were not included if they were using oral contraceptives or hormone therapy, or if they had cancer, diabetes mellitus, chronic hepatitis, or thyroid disease. Information on potential breast cancer risk factors including body size, physical activity, and reproductive factors were obtained using a self-administered questionnaire. The phase of menstrual cycle at blood donation, categorized in early follicular, late follicular, peri-ovulatory, midluteal, or other luteal, was used for adjustment together with age. Estradiol level was significantly inversely associated with body mass index (BMI), while testosterone and DHEAS levels were significantly positively associated with BMI; the geometric mean of estradiol in women with BMI at or above 24 kg/m2 was about 25% lower than that in women with BMI below 18 kg/m2. The geometric means of testosterone and DHEAS were 31% and 24% higher, respectively, in women in the high BMI group. Nulliparous women had significantly higher testosterone levels than parous women. Breastfeeding was associated with decreased levels of testosterone and DHEAS. Physical activity, age at menarche, number of births, and age at first birth were not significantly associated with these hormone levels. A reduced breast cancer risk of obese premenopausal women may be due, in part, to a decreased estradiol level. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B117.

Consumption of sweet foods and breast cancer risk: a case–control study of women on Long Island, New York

Several epidemiologic studies have reported a positive association between breast cancer risk and high intake of sweets, which may be due to an insulin-related mechanism. We investigated this association in a population-based case-control study of 1,434 cases and 1,440 controls from Long Island, NY. Shortly after diagnosis, subjects were interviewed in-person to assess potential breast cancer risk factors, and self-completed a modified Block food frequency questionnaire, which included 11 items pertaining to consumption of sweets (sweet beverages, added sugars, and various desserts) in the previous year. Using unconditional logistic regression models, we estimated the association between consumption of sweets and breast cancer. Consumption of a food grouping that included dessert foods, sweet beverages, and added sugars was positively associated with breast cancer risk [adjusted odds ratio (OR) comparing the highest to the lowest quartile: 1.27, 95% confidence interval (CI): 1.00-1.61]. The OR was slightly higher when only dessert foods were considered (OR: 1.55, 95% CI: 1.23-1.96). The association with desserts was stronger among pre-menopausal women (OR: 2.00, 95% CI: 1.32-3.04) than post-menopausal women (OR: 1.40, 95% CI: 1.07-1.83), although the interaction with menopause was not statistically significant. Our study indicates that frequent consumption of sweets, particularly desserts, may be associated with an increased risk of breast cancer. These results are consistent with other studies that implicate insulin-related factors in breast carcinogenesis.

No association of miscarriage and BRCA carrier status in Pakistani breast/ovarian cancer patients with a history of parental consanguinity

To the editor About 80% of breast and ovarian cancer families and about 50% of site-specific breast cancer families are due to germ line mutations in either BRCA1 (MIM 113705) or BRCA2 (MIM 600185) [1–3]. Women carrying a pathogenic mutation in BRCA1 or BRCA2 face average lifetime risks of 65% and 45%, respectively, of developing breast cancer, and corresponding ovarian cancer risks of 39% and 11% [4]. In humans, almost all BRCA carriers have been found to be heterozygous [5, 6]. The lack of viable homozygous BRCA mutation carriers in humans suggests that homozygous fetuses may be more susceptible to spontaneous abortions. Further evidence for this hypothesis comes from in vivo animal studies showing that mice homozygous for mutations in the BRCA1 or BRCA2 gene die early in embryogenesis [7, 8]. Two recent studies have explored the impact of BRCA mutation status on the occurrence of miscarriages. One study included BRCA carriers of Ashkenazi Jewish descent [9], and the other included mutation carriers from United States and Canada [10]. Neither study found a significant difference in the rate of miscarriage between BRCA carriers and non-carriers. We conjectured that miscarriages may occur more frequently in BRCA carriers from consanguineous parents since their offspring are more often homozygous by descent compared to those of unrelated parents, and living homozygous BRCA mutation carriers have not been observed. To explore this question, we studied the rates of miscarriages in Pakistani BRCA mutation carriers and non-carriers with a history of parental consanguinity. Pakistan has one of the highest rates of consanguinity in the world (range 60–70%) [11, 12]. Breast and/or ovarian cancer families were recruited at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, between June 2001 and November 2004. Of the 165 female index patients, 30 carried a deleterious BRCA mutation, and 135 were without any identifiable mutation. All families, screening methods and mutations have been described previously [13]. Four additional families carrying a deleterious BRCA mutation identified recently were also included in this study. Relevant information regarding potential breast cancer risk factors including family history of cancer, hormone use, reproductive history, medical history and life style factors was collected by interview-administered questionnaires. Detailed information on the outcome of each pregnancy (year of each pregnancy, number of miscarriages including spontaneous and therapeutic abortions, number of still and live born), and parental consanguinity was collected. Spontaneous abortion was defined as loss of a pregnancy before the completion of 20 gestational weeks from the M. U. Rashid F. Rasheed F. Sultan Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan

Relationship between Histamine2-Receptor Antagonist Medications and Risk of Invasive Breast Cancer

Histamine(2)-receptor antagonist (H(2) blocker) medications are used to treat heartburn, gastroesophageal reflux disease, and ulcers. Some H(2) blockers, specifically cimetidine and ranitidine, also increase serum prolactin concentrations. Given the positive relationship between prolactin levels and postmenopausal breast cancer risk, use of H(2) blockers is a potential breast cancer risk factor. The few previous studies evaluating this association have been null but have been limited by small sample sizes, and none have evaluated risk by either histologic type or estrogen receptor/progesterone receptor status. Combining data from two population-based case-control studies conducted in western Washington, we assessed the relationship between use of H(2) blockers and risk of different types of breast cancer among 1,941 cases and 1,476 controls 55 to 79 years old. Odds ratios and 95% confidence intervals (95% CI) were calculated using polytomous logistic regression. Current use of H(2) blockers overall, cimetidine, and famotidine was not associated with an increased risk of either invasive ductal or invasive lobular breast cancer. Current users of ranitidine had a 2.2-fold (95% CI, 1.1-4.3) increased risk of ductal carcinoma that was confined to a 2.4-fold (95% CI, 1.2-4.9) increased risk of estrogen receptor-positive/progesterone receptor-positive ductal carcinoma. Use of H(2) blockers in general is not associated with an increased risk of breast cancer, although current use of ranitidine may increase risk of hormone receptor-positive ductal carcinoma. Further studies to confirm this finding are warranted.

Relationship between Age Maximum Height Is Attained, Age at Menarche, and Age at First Full-Term Birth and Breast Cancer Risk

Several pubertal and reproductive events are well established risk factors for breast cancer. Age maximum height attained is an understudied potential breast cancer risk factor that may affect risk through mechanisms different from those of other pubertal and reproductive events. We assessed the relationships between different pubertal/reproductive events and risk of different types of breast cancer in a prospective cohort of 27,536 women. Women were recruited between 2000 and 2002 and completed a mailed questionnaire. As of 2005, 585 women were diagnosed with breast cancer. Using a Cox proportional hazards model, women who reached their maximum height at <or=12 years of age had a 1.4-fold [95% confidence interval (95% CI), 1.0-1.8] increased risk of breast cancer compared with women who reached their maximum height at >or=17 years of age (P(trend) = 0.04). This association was primarily limited to more aggressive tumors, specifically those that were estrogen receptor-negative (hazard ratio, 1.9; 95% CI, 1.0-3.9) and diagnosed at a regional or distant stage (hazard ratio, 1.8; 95% CI, 1.0-3.1). There was no difference in the relation of age at menarche with breast cancer by tumor stage, whereas late age at first full-term pregnancy primarily increased risks of less-aggressive disease, including lobular, estrogen receptor-positive, and localized stage tumors. Age at maximum height seems to be an independent risk factor for breast cancer that is more strongly associated with relatively aggressive tumors that have a poorer prognosis compared with the types of tumors that are associated with ages at menarche and first full-term birth.

Occupation and breast cancer risk in Polish women: A population‐based case‐control study

The etiology of breast cancer is not well understood and the role of occupational exposures in breast carcinogenesis is still uncertain. The population-based case-control study included 2,386 incident breast cancer cases diagnosed in 2000-2003, and 2,502 controls. Lifetime occupational histories and information on other potential breast cancer risk factors were obtained through personal interviews. Conditional logistic regression analyses calculated odds ratios (ORs) associated with various occupations and industries after control for potential confounders. We found statistically significant excesses of breast cancer among engineers (OR=2.0; 95% CI: 1.0-3.8), economists (2.1; 1.1-3.8), sales occupations-retail (1.2; 1.0-1.5), and other sales occupations (1.2; 1.0-1.5). Industries showing significantly elevated risks included special trade contractors (2.2; 1.2-4.3), electronic and electric equipment manufacturers (1.7; 1.1-2.7); and public administration/general government n.e.c. (2.7; 1.3-5.7). Each of these findings was supported by a statistically significant positive trend for duration of employment (P<0.05). A decreased breast cancer risk was observed in janitors and cleaners (0.7; 0.5-0.8). In this study, we found few associations for breast cancer and occupations or industries. The suggestive findings for the electronic and electric equipment manufacturing industry and for the occupations with potential exposure to magnetic fields deserve further evaluation.

Departure from multiplicative interaction for catechol-O-methyltransferase genotype and active/passive exposure to tobacco smoke among women with breast cancer

BackgroundWomen with homozygous polymorphic alleles of catechol-O-methyltransferase (COMT-LL) metabolize 2-hydroxylated estradiol, a suspected anticarcinogenic metabolite of estrogen, at a four-fold lower rate than women with no polymorphic alleles (COMT-HH) or heterozygous women (COMT-HL). We hypothesized that COMT-LL women exposed actively or passively to tobacco smoke would have higher exposure to 2-hydroxylated estradiol than never-active/never passive exposed women, and should therefore have a lower risk of breast cancer than women exposed to tobacco smoke or with higher COMT activity.MethodsWe used a case-only design to evaluate departure from multiplicative interaction between COMT genotype and smoking status. We identified 502 cases of invasive incident breast cancer and characterized COMT genotype. Information on tobacco use and other potential breast cancer risk factors were obtained by structured interviews.ResultsWe observed moderate departure from multiplicative interaction for COMT-HL genotype and history of ever-active smoking (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 0.7, 3.8) and more pronounced departure for women who smoked 40 or more years (aOR = 2.3, 95% CI: 0.8, 7.0). We observed considerable departure from multiplicative interaction for COMT-HL genotype and history of ever-passive smoking (aOR = 2.0, 95% CI: 0.8, 5.2) or for having lived with a smoker after age 20 (aOR = 2.8, 95% CI: 0.8, 10).ConclusionWith greater control over potential misclassification errors and a large case-only population, we found evidence to support an interaction between COMT genotype and tobacco smoke exposure in breast cancer etiology.

Fat Intake Is Associated with Serum Estrogen and Androgen Concentrations in Postmenopausal Japanese Women

A reduction in fat intake has been associated with decreased estrogen levels in dietary intervention studies. However, previous cross-sectional studies conducted mainly among Western populations did not find a positive association between fat intake and postmenopausal estrogen levels. This study examined the cross-sectional association of fat intake with serum levels of estrone, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEAS) in women. Study subjects were 324 healthy postmenopausal Japanese women. Diet including fat intake was assessed by a validated semiquantitative FFQ. After controlling for age and other potential breast cancer risk factors, serum estrone was positively associated with the percentage of energy from total fat (P = 0.04). The associations of serum estrone with monounsaturated fat and polyunsaturated fat were of borderline significance (P = 0.05). Serum DHEAS was positively associated with the percentage of energy from total fat (P = 0.007), saturated fat (P = 0.009), monounsaturated fat (P = 0.006), and polyunsaturated fat (P = 0.04). Serum estrone and DHEAS concentrations increased 11.8 and 9.3%, respectively, with a 5% increase in the percentage of energy from total fat. These data suggest that a high intake of fat is associated with higher serum levels of estrone and DHEAS in postmenopausal women.

Personality characteristics and the risk of breast cancer: A prospective cohort study

Various personality characteristics have been suggested to increase the risk of breast cancer but reliable epidemiologic data on this issue are limited. We prospectively investigated the relationship between personality characteristics and the risk of breast cancer in 12,499 Finnish women aged 18 years or more. In health questionnaires in 1975 and 1981, these women completed at least one of the following personality scales: Eysenck extroversion, Bortner type A behaviour and author-constructed measure of hostility. They also reported about other potential breast cancer risk factors. From 1976-1996, 253 cases of breast cancer were identified by record linkage with the Finnish Cancer Registry. Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The multivariable HRs of breast cancer for women with intermediate level (scores 3-6) and high level (7-9) of extroversion in 1975 were 1.18 (95% CI 0.87-1.60) and 0.97 (95% CI 0.64-1.47), respectively, compared to those with low level (0-2). These results remained unaltered when the level of extroversion was determined as the average of the 1975 and 1981 reports. There was also no increase in breast cancer risk in relation to type A behaviour and hostility. Furthermore, we observed no substantial joint effects of personality characteristics on the risk of breast cancer. In conclusion, our data do not support the existence of an important role for personality in the aetiology of breast cancer. These findings are reassuring to those who have believed the contrary.

Organochlorines and breast cancer: effect of exposure to dieldrin on risk and survival

Some organochlorines have weak estrogenic activity, and may therefore interfere with breast cancer risk and survival. We assessed prospectively risk and prognosis of breast cancer in relation to serum concentrations of several compounds, which have shown to be estrogenic in vitro and in vivo. Study participants (7712 women) donated blood twice (1976-1978 and 1981-1983) and were followed for 17 years with regard to development of breast cancer. Information on potential breast cancer risk factors and prognostics were obtained through standardized questionnaires and by linkage to the Danish Breast Cancer Cooperative Group. Breast cancer risk associated with baseline exposure in 1976-1978, and repeated measurements of organochlorines (average concentration of the two measurements) was examined in two cohort-nested case-control studies, including 240 cases and 477 controls, and 155 cases and 274 controls, respectively. The cases served as a cohort in the survival analysis, in which the average duration of follow up to death was 86 and 79 months after the first and second sampling. The most consistent finding observed was dieldrin's adverse effect on breast cancer risk as well as prognosis. More than a twofold increased risk was found among women with the highest baseline concentration compared with those with the lowest, and a significant trend was apparent. A high serum dieldrin concentration was also significantly associated with an increased overall mortality, being threefold for baseline measurements and almost sixfold when repeated measurements was assessed. Similar results were obtained when using breast cancer recurrence and/or death caused by breast cancer as end-point.

Relations of insulin resistance and serum concentrations of estradiol and sex hormone-binding globulin to potential breast cancer risk factors.

There is a hypothesis that hyperinsulinemia or insulin resistance may be a mediator for breast cancer risk factors. On the other hand, some, but not all, of the well‐known risk factors of breast cancer have been associated with serum estrogen concentrations. We assessed the relationships of potential breast cancer risk factors to indicators of insulin resistance, fasting plasma insulin concentration and homeostasis model assessment insulin resistance (HOMA‐R), in 88 postmenopausal Japanese women. We also examined whether insulin resistance would explain the association of breast cancer risk factors with serum estradiol and sex hormone‐binding globulin (SHBG). Information on potential breast cancer risk factors, such as demographic characteristics, smoking and drinking habits, diet, exercise, menstrual and reproductive factors, was obtained by self‐administered health questionnaire including a validated semiquantitative food frequency questionnaire. Body mass index (BMI) was significantly correlated with the ratio of estradiol to SHBG (Spearman r=0.30, P=0.0004), fasting plasma insulin (r=0.45) and HOMA‐R (r=0.43, P=0.0001) after controlling for age. The correlations were still significant between BMI and estradiol/SHBG ratio (r=0.21, P=0.047) after controlling for fasting plasma insulin and between BMI and fasting plasma insulin (r=0.40, P=0.0001) as well as HOMA‐R (r=0.38, P=0.0003) after controlling for estradiol/SHBG ratio. There is a possibility that effect of BMI on breast cancer risk is mediated by both insulin resistance and estrogen metabolism.

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.

Association of family history and other risk factors with breast cancer risk (Sweden).

Women with a family history of breast cancer have an increased risk for the disease. However, the combined impact of family history and other risk factors on breast cancer risk is unclear. We conducted a large epidemiologic study to examine this issue. METHODS. In a population-based case-control study in all of Sweden, 3,345 women aged 50 to 74 years with invasive breast cancer (84 percent of all eligible), and 3,454 controls of similar age (82 percent of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on potential breast cancer risk factors. Odds ratios (OR) and 95 percent confidence intervals (CI) were estimated through multiple logistic regression. Women with a history of breast cancer in any first-degree relative had an increased risk of breast cancer compared with those without such a history (OR = 1.96, CI = 1.67-2.30). There was no clear indication of a differential impact of hormonal risk factors (age at menarche, parity, age at first birth, age at menopause, use of exogenous hormones, and weight gain) or body build at age seven among women with and without a positive family history. Yet, benign breast disease and height clearly were related to breast cancer risk in subjects without a family history, whereas seemingly not so in women with a family history. Formal tests for interaction between family history and these factors, however, did not prove statistically significant. Our findings indicate that established risk factors entail similar associations with breast cancer risk among women with and without family history of the disease.

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

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. 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. 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. 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.