Tubal sterilization in relation to breast cancer risk

Tubal sterilization methods may damage surrounding tissue, potentially disrupting the ovarian blood supply and hormonal functioning, and may decrease breast cancer risk. We examined this hypothesis, within the Nurses' Health Study, among 77,511 women, aged 30-55 years and free of cancer at the start of follow-up in 1976. We documented 4,176 cases of invasive breast cancer from 1976 to 2000. Cox proportional hazards models, adjusting for multiple breast cancer risk factors, provided rate ratios (RR) and 95% confidence intervals (CI). Overall, tubal sterilization was not associated with breast cancer risk (RR=0.95, 95% CI=0.88-1.03). However, tubal sterilizations performed from 1970 to 1974 were inversely associated with risk (RR=0.84, 95% CI=0.73-0.97), while procedures performed in other years were not associated with risk. Among women with procedures performed in 1970-1974, those who were >or=35 years old at the time of sterilization were at the lowest risk (RR=0.81, 95% CI=0.66-0.98), while younger women had a suggested decreased risk (RR=0.87, 95% CI=0.72-1.06). Overall, tubal sterilization was not associated with breast cancer risk. However, a modest inverse association was observed at a time when the potentially destructive unipolar electrocautery method was commonly used, providing some support for an association between lower lifetime exposure to hormones and a decreased risk of breast cancer.     

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.     

Tubal ligation in relation to menopausal symptoms and breast cancer risk

Background:

Local inflammation after tubal ligation may affect ovarian function and breast cancer risk.

Methods:

We analysed tubal ligation, menopausal characteristics, and breast cancer risk in the Sister Study cohort (N=50 884 women).

Results:

Tubal ligation was associated with hot flashes (hazard ratio (HR) 1.09; 95% confidence interval (CI): 1.06–1.12) but not menopausal age (HR 0.99; 95% CI: 0.96–1.02). Tubal ligation did not have an impact on breast cancer overall (HR 0.95; 95% CI: 0.85–1.06), but had a suggested inverse relation with oestrogen receptor+/progesterone receptor+ invasive tumours (HR 0.84; 95% CI: 0.70–1.01), possibly because of subsequent hysterectomy/bilateral oophorectomy.

Conclusion:

Tubal ligation does not influence overall breast cancer risk.     

Prospective study of alcohol consumption and breast cancer risk in Japanese women

Epidemiologic evidence is lacking for the association between alcohol consumption and the risk of breast cancer in Japanese women. We addressed this association in a prospective cohort study with an average follow-up of 7.6 years. At baseline (1988-1990), cohort participants completed a self-administered questionnaire that included alcohol use, reproductive history and hormone use. The women were followed up for breast cancer incidence through December 31, 1997. Cox proportional hazards models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer incidence and any association with alcohol consumption. During a follow-up of 271,412 person-years, we identified 151 women with breast cancer, of whom 45 were current drinkers and 11 drank > or =15 g of alcohol/day. After adjustment for age and other potential risk factors for breast cancer, the RR for current drinkers was 1.27 (95% CI 0.87-1.84) compared to nondrinkers. Average alcohol intake of <15 g/day did not significantly increase the risk for breast cancer. However, risk was significantly increased for women who consumed > or =15 g/day of alcohol (RR = 2.93, 95% CI 1.55-5.54). Age at starting drinking and frequency of consumption per week were not significantly associated with breast cancer risk. Our cohort study demonstrated that Japanese women who consume at least a moderate amount of alcohol have an increased risk of breast cancer.     

Body mass index,height, and postmenopausal breast cancer mortality in a prospective cohort of US women

Objective: Epidemiologic evidence suggests a positive association between body mass, adult height, and postmenopausal breast cancer. However, most studies have not been large enough to examine the association across a very wide range of body mass or height, and few studies have assessed the relationship between body mass or height and postmenopausal breast cancer mortality. Methods: The relation between body mass index (BMI) and height and postmenopausal breast cancer mortality was examined in the American Cancer Society's Cancer Prevention Study II (CPS-II), a large prospective mortality study of US adults enrolled in 1982. After 14 years of follow-up, 2852 breast cancer deaths were observed among 424,168 postmenopausal women who were cancer-free at interview. Cox proportional hazards modeling was used to estimate relative risks and to control for potential confounding. Results: Breast cancer mortality rates increased continually and substantially with increasing BMI (rate ratio (RR) = 3.08, 95% confidence interval (CI) = 2.09–4.51 for BMI 40.0 compared to BMI 18.5–20.49). If causal, the multivariate-adjusted RR estimates in this study correspond to approximately 30–50% of breast cancer deaths among postmenopausal women in the US population being attributable to overweight. Breast cancer mortality also increased with increasing height up to 66 inches with RR = 1.64, (95% CI = 1.23–2.18) in women 66 inches tall compared to those < 60 inches. Conclusions: Postmenopausal obesity is an important and potentially avoidable predictor of fatal breast cancer in this study. These results underscore the importance of maintaining moderate weight throughout adult life.     

Breast cancer mortality in relation to self-reported use of breast self-examination. A cohort study of 450,000 women

The benefits of breast self-examination (BSE) for reducingmortality from breast cancer are uncertain. We conductedan analysis of the relationship between self-reported practicingof BSE and mortality from breast cancer over13 years in a cohort of over 548,000women. The report of practicing BSE was unrelatedto breast cancer mortality. There was a smallbeneficial effect in those women who were thethinnest, but this effect was small and notstatistically significant. BSE was otherwise equally ineffective insubgroups defined by obesity level and family historyof breast cancer. We conclude that BSE, aspracticed by American women in 1959, did notreduce the risk of mortality from breast cancer.     

Breast density and risk of breast cancer

Early studies reported a 4- to 6-fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case-control studies, we took advantage of a population-based screening program to study density and breast cancer incidence in a cohort design. In the Capital Region, Denmark, women aged 50 to 69 are invited to screening biennially. Women screened November 2012 to December 2017 were included, and classified by BI-RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RRs) and 95% confidence intervals (CI) were compared across density groups using Poisson-regression. We included 189 609 women; 1 067 282 person-years; and 4110 incident breast cancers/DCIS. Thirty-three percent of women had BI-RADS density code 1; 38% code 2; 24% code 3; 4.7% code 4; and missing 0.3%. Using women with BI-RADS density code 1 as baseline; women with code 2 had RR 1.69 (95% CI 1.56-1.84); women with code 3, RR 2.06 (95% CI 1.89-2.25); and women with code 4, RR 2.37 (95% CI 1.05-2.74). Results differed between observations accumulated during screening and above screening age. Our results indicated less difference in breast cancer risk across level of breast density than normally stated. Translated into absolute risk of breast cancer after age 50, we found a 6.2% risk for the one-third of women with lowest density, and 14.7% for the 5% of women with highest density.     

Childhood and adult milk consumption and risk of premenopausal breast cancer in a cohort of 48,844 women - the Norwegian women and cancer study

The belief that life stress enhances breast cancer is common, but there are few prospective epidemiological studies on the relationship of life stress and breast cancer. We have investigated the association between stress of daily activities (SDA) and breast-cancer risk in a prospective cohort study of 10,519 Finnish women aged 18 years or more. SDA measures a subject's own appraisal of daily stress. It was assessed in 1975 and 1981 by a self-administered questionnaire, which also provided information on subject characteristics and other known breast-cancer risk factors. Follow-up data for breast cancer from 1976 to 1996 were attained through record linkage to the Finnish Cancer Registry. Study subjects were divided into 3 groups based on their SDA scores in 1975: no stress (23% of subjects), some stress (68%) and severe stress (9%). Hazard ratios (HRs) and respective 95% confidence intervals (CIs) for incidence of breast cancer by level of SDA were obtained from the Cox proportional hazards model. We identified 205 incident breast cancers in the cohort. Multivariable-adjusted HRs for breast-cancer risk were 1.00 (reference), 1.11 (95% CI 0.78-1.57) and 0.96 (95% CI 0.53-1.73) by increasing level of stress. Neither shifting of the SDA cut-off points nor restricting the analysis to women who reported the same level of SDA in 1975 and 1981 materially altered the results. We found no evidence of an association between self-perceived daily stress and breast-cancer risk.     

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.     

Birth outcome in women with breast cancer

We investigated whether maternal breast cancer affects birth outcome in a nationwide cohort study of 695 births from 1973 to 2002 of women with breast cancer with respect to preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33 443 births from unaffected mothers. There was no excess risk of adverse birth outcome for the 216 newborns of women with breast cancer before pregnancy. Stratification by mother's treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 (95% confidence interval (CI): 3.8-17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed in the 2 years from time of delivery, the PR of preterm birth was 1.4 (95% CI: 1.0-2.0), and the PR of low birth weight at term for boys was 2.9 (95% CI: 1.3-6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for breast cancer patients.     

Breast cancer risk factors and mammographic breast density in women over age 70

SummaryBackground Breast density is a strong risk factor for breast cancer, but little is known about factors associated with breast density in women over 70.Methods Percent breast density, sex hormone levels and breast cancer risk factor data were obtained on 239 women ages 70–92 recruited from 1986 to 1988 in the United States. Multivariable linear regression was used to develop a model to describe factors associated with percent density.Results Median (range) percent density among women was 23.7% (0–85%). Body mass index (β= −0.345, p<0.001 adjusted for age and parity) and parity (β= −0.277, p<0.001 adjusted for age and BMI) were significantly and inversely associated with percent breast density. After adjusting for parity and BMI, age was not associated with breast density (β=0.05, p=0.45). Parous women had lower percent density than nulliparous women (23.7 versus 34.7%, p=0.005). Women who had undergone surgical menopause had greater breast density than those who had had a natural menopause (33.4 versus 24.8%, p=0.048), as did women who were not current smokers (26.0 versus 17.3% for smokers, p=0.02). Breast density was not associated with age at menarche, age at menopause, age at first birth, breastfeeding, estrogen levels or androgen levels. In a multivariable model, 24% of the variance in percent breast density was explained by BMI (β= −0.35), parity (β=−0.29), surgical menopause (β=0.13) and current smoking (β= −0.12).Conclusion Factors associated with breast density in older, post-menopausal women differ from traditional breast cancer risk factors and from factors associated with breast density in pre-menopausal and younger post-menopausal women.     

Endogenous sex hormones and subsequent breast cancer in premenopausal women

Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at -80 degrees C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol-glucoronide, progesterone, 17-OH-progesterone, sex hormone-binding globulin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fifty-five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11-7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% CI = 0.15-1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.     

Active and passive smoking and breast cancer risk in middle-aged Japanese women

To examine the hypothesis that tobacco smoke is associated with the risk of female breast cancer, we estimated the relative risks of active and passive smoke in middle-aged Japanese women in a population-based prospective study. The cohort consisted of residents in 4 public health center areas, aged 40 to 59 years. A self-administered questionnaire survey was conducted in 1990. This analysis included 21,805 subjects, 180 of whom had developed breast cancer by December 31, 1999. When the reference was defined as never-active smokers without passive smoking, adjusted relative risks (RRs) were 1.9 (95% confidence interval [CI] = 1.0-3.6) in current active smokers, 1.2 (95% CI = 0.4-4.0) in ex-active smokers and 1.2 (95% CI = 0.8-1.6) in never-active smokers with passive smoking. The elevated risk for ever-smokers was clearly observed in premenopausal women at baseline (RR = 3.9, 95% CI = 1.5-9.9) but not in postmenopausal women (RR = 1.1, 95% CI = 0.5-2.5). In never-active smokers, the adjusted RR for passive smoking, residential or occupational/public tobacco smoke exposure was 1.1 (95% CI = 0.8-1.6). In premenopausal women, passive smoking increased the risk (RR = 2.6; 95% CI = 1.3-5.2) but not in postmenopausal women (RR = 0.7; 95% CI = 0.4-1.0). We conclude that tobacco smoking increases the risk of female breast cancer in premenopausal women.     

Dietary acrylamide intake and risk of breast cancer in the UK women's cohort

Background:

No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.

Methods:

A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women''s Cohort Study followed up for a median of 11 years.

Results:

In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day⁻¹, 95% CI: 0.98–1.18, P_trend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, P_trend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, P_trend=0.99).

Conclusions:

There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.     

Gender of offspring and long-term maternal breast cancer risk

Gender of offspring is influenced by maternal hormonal level during pregnancy, which is believed to influence the subsequent maternal breast cancer risk. However, analysing national birth and cancer registrations in a cohort of 998,499 women, we found no association between gender of offspring and subsequent breast cancer risk.     

Changes in mammographic density over time in breast cancer cases and women at high risk for breast cancer

High mammographic breast density is one of the strongest intermediate markers of breast cancer risk, and decreases in density over time have been associated with decreases in breast cancer risk. Using repeated measures of mammographic density in a cohort of high‐risk women, the Women at Risk (WAR) cohort at Columbia University Medical Center (N = 2670), we examined whether changes in prediagnostic mammographic density differed among 85 prospectively‐ascertained breast cancer cases and 85 age‐matched controls, using a nested case–control design. Median age at first mammogram was 51 years (range, 29–77 years), with a median of 4 years between first and second prediagnostic mammogram (range, 1–15 years). Using linear regression with change in percent density as the outcome, we found that in women who did not go on to be diagnosed with breast cancer, change in percent density decreased as time between first and second mammogram increased (β = ?1.62% per year, p = 0.004). However, in women who did go on to be diagnosed with breast cancer, there was no overall change in percent density associated with time between first and second mammogram (β = 0.29% per year, p = 0.61); the change over time was statistically significantly different between cases versus controls (p <0.009). If replicated in larger cohorts, these results suggest that within‐individual changes in mammographic density as measured by percent density may be a useful biomarker of breast cancer risk.     

Choline and betaine intake and risk of breast cancer among post-menopausal women

Background:

Choline and betaine, similar to folate, are nutrients involved in one-carbon metabolism and hypothesised to reduce breast cancer risk. No prospective study among post-menopausal women has examined choline and betaine intakes in relation to breast cancer risk.

Methods:

We examined the intake of choline and betaine and breast cancer risk among 74 584 post-menopausal women in the Nurses'' Health Study. Nutrient intake was assessed using a validated food-frequency questionnaire six times since 1984. During 20 years of follow-up from 1984 until 2004, we documented 3990 incident cases of invasive breast cancer.

Results:

Overall, choline (mean±s.d.; 326±61 mg per day) and betaine (104±33 mg per day) intake was not associated with a reduced risk of post-menopausal breast cancer. Participants in the highest quintile of intakes had multivariate relative risks of 1.10 (95% confidence interval (95% CI): 0.99–1.22; P-value, test for trend=0.14) for choline and 0.98 (95% CI: 0.89–1.09; P-value, test for trend=0.96) for betaine, compared with those in the lowest quintiles of intakes. The results were similar in breast cancer stratified by hormone receptor (oestrogen receptor/progesterone receptor) status. The association between choline intake and breast cancer risk did not differ appreciably by alcohol intake (non-drinker, <15 or 15+ g per day) or several other breast cancer risk factors, including family history of breast cancer, history of benign breast disease, body mass index, post-menopausal hormone use, and folate intake.

Conclusion:

We found no evidence that higher intakes of choline and betaine reduce risk of breast cancer among post-menopausal women.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.     

Birthweight, childhood growth and risk of breast cancer in a British cohort

We have examined the relationship between birthweight and risk of breast cancer, taking into account growth in childhood, using data on a total of 2221 women born in 1946 and followed up to 1997. Thirty-seven breast cancers occurred during follow-up. There was evidence of greater risk of breast cancer with greater birthweight (rate ratio = 1.76 (95% CI: 0.92, 3.35) for birthweight >/= 3.5 kg vs birthweight < 3.5 kg), which was more marked at pre-menopausal ages (RR = 2.31, 95% CI: 0.93, 5.74). The relation with birthweight was not substantially confounded by any of the measured adult risk factors. A significant interaction was observed between the effects of birthweight and height at age 7 years. Relative to those born lighter than 3.5 kg, women who were heavy at birth (>/= 3.5 kg) and short or average at 7 years (< 1.22 m) had a 21% increase in breast cancer rates (RR = 1.21; 95% CI = 0.49-2.99), while women who were heavy at birth (>/= 3.5 kg) but tall at 7 years (>/= 1.22 m) had a four-fold increase (RR = 4.01; 95% CI = 1.82-8.83). These results suggest that the effect of birthweight on breast cancer risk may be modulated by childhood growth.