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.     

Employment and social benefits up to 10 years after breast cancer diagnosis: a population-based study

Background:

Little is known about employment outcomes after breast cancer (BC) beyond the first years after treatment.

Methods:

Employment outcomes were compared with a general population comparison group (N=91 593) up to 10 years after BC for 26 120 patients, diagnosed before age 55 between 2000–2005, with income and social benefits data from Statistics Netherlands. Treatment effects were studied in 14 916 patients, with information on BC recurrences and new cancer events.

Results:

BC survivors experienced higher risk of losing paid employment (Hazard Ratio (HR): 1.6, 95% Confidence Interval (95% CI) 1.4–1.8) or any work-related event up to 5–7 years (HR 1.5, 95% CI 1.3–1.6) and of receiving disability benefits up to 10 years after diagnosis (HR 2.0, 95% CI 1.6–2.5), with higher risks for younger patients. Axillary lymph node dissection increased risk of disability benefits (HR 1.5, 95% CI 1.4–1.7) or losing paid employment (HR 1.3, 95% CI 1.2–1.5) during the first 5 years of follow-up. Risk of disability benefits was increased among patients receiving mastectomy and radiotherapy (HR 1.2; 95% CI 1.1–1.3) and after chemotherapy (HR 1.7; 95% CI 1.5–1.9) during the first 5 years after diagnosis.

Conclusions:

BC treatment at least partly explains the increased risk of adverse employment outcomes up to 10 years after BC.     

γ-Glutamyl transferase and breast cancer risk

Background:

It has been reported that there is an increased risk of cancer in individuals with elevated levels of serum γ-glutamyl transferase (GGT).

Methods:

In the Guernsey Breast Cancer Cohort Study, GGT was measured in sera from 1803 normal women. Among these women, 251 subsequently developed cancer, of whom 96 developed breast cancer.

Results:

After adjustment for age at entry, height, weight, age at menarche and first birth with nulliparity, there was a highly significant relationship between elevated GGT and breast cancer risk. In the highest quartile, the hazard ratio (HR) was 2.17 (95% confidence interval (CI): 1.19, 3.93). When subdivided by menopausal status, there was a reduced non-significant effect in postmenopausal women, whereas for premenopausal women in the highest quartile, HR was 3.81 (95% CI: 1.37, 10.59). Premenopausal women with serum GGT levels above the normal range had a significantly elevated HR of 4.90 (95% CI: 1.86, 12.94).

Conclusions:

These results suggest that premenopausal women with high normal (above median) serum GGT or elevated levels (⩽40 IU l⁻¹) are at increased risk of breast cancer and might benefit from close surveillance, possibly with breast magnetic resonance imaging scans. Serum GGT may mark previous exposure to carcinogens and lead to the identification of DNA adducts involved in mammary carcinogenesis.     

Dietary patterns and survival in German postmenopausal breast cancer survivors

Background:

Research on the association between dietary patterns and breast cancer survival is very limited.

Methods:

A prospective follow-up study was conducted in Germany, including 2522 postmenopausal breast cancer patients diagnosed in 2001–2005 with available food frequency questionnaire data. Vital status, causes of death, and recurrences were verified through the end of 2009. Principle component factor analysis was used to identify pre-diagnostic dietary patterns. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards models.

Results:

Two major dietary patterns were identified: ‘healthy'' (high intakes of vegetables, fruits, vegetable oil, sauces/condiments, and soups/bouillons) and ‘unhealthy'' (high intakes of red meat, processed meat, and deep-frying fat). Increasing consumption of an ‘unhealthy'' dietary pattern was associated with an increased risk of non-breast cancer mortality (highest vs lowest quartile: HR, 3.69; 95% CI, 1.66–8.17; P-trend <0.001). No associations with breast cancer-specific mortality and breast cancer recurrence were found. The ‘healthy'' dietary pattern was inversely associated with overall mortality (HR, 0.74; 95% CI, 0.47–1.15; P-trend=0.02) and breast cancer recurrence (HR, 0.71; 95% CI, 0.48–1.06; P-trend=0.02) in stage I–IIIa patients only.

Conclusion:

Increasing intake of an ‘unhealthy'' pre-diagnostic dietary pattern may increase the risk of non-breast cancer mortality, whereas increasing intake of a ‘healthy'' pattern may reduce the risk of overall mortality and breast cancer recurrence.     

Anthropometric measures and epithelial ovarian cancer risk among Chinese women: results from the Shanghai Women's Health Study

Background:

Studies of anthropometric measures and ovarian cancer risk have predominantly included women of European descent with mixed findings.

Methods:

Data from the prospective Shanghai Women''s Health Study (SWHS) were used to evaluate associations between anthropometric measures and risk of epithelial ovarian cancer (EOC). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.

Results:

A total of 152 EOC cases occurred among 70 258 women. Increasing quartiles of weight, hip circumference, and weight gain during adulthood were associated with significantly increased EOC risks. Body mass index (BMI) was also associated; overweight (25⩽BMI<29.99) and obese women (BMI⩾30.0) had significantly increased risks (HR: 1.49, 95% CI: 1.05, 2.13, and HR: 2.42, 95% CI: 1.37, 4.28, respectively). No significant associations were observed for height, waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHER).

Conclusion:

Results from this large prospective study of Chinese women support the hypothesis that general adiposity contributes to the aetiology of ovarian cancer.     

Diabetes and breast cancer risk: a meta-analysis

Background:

The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research.

Methods:

A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk.

Results:

Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)).

Conclusion:

The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.     

Intake of coffee,caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer

Background:

Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously.

Methods:

Prospective cohort of 23 356 postmenopausal women with 471 Type I and 71 Type II EC cases.

Results:

Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ⩽1 cup per month: 95% confidence interval (CI): 0.47–0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50–1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m⁻² (RR=0.56; 95% CI: 0.36–0.89).

Conclusion:

Coffee may protect against Type I EC in obese postmenopausal women.     

A population-based cohort study on sun habits and endometrial cancer

Background:

No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.

Methods:

A population-based cohort study of 29 508 women who answered a questionnaire in 1990–92, of whom 24 098 responded to a follow-up enquiry in 2000–02. They were followed for an average of 15.5 years.

Results:

Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4–0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3–0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5–1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).

Conclusion:

Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.     

Combined effects of endogenous sex hormone levels and mammographic density on postmenopausal breast cancer risk: results from the Breakthrough Generations Study

Background:

Mammographic density and sex hormone levels are strong risk factors for breast cancer, but it is unclear whether they represent the same aetiological entity or are independent risk factors.

Methods:

Within the Breakthrough Generations Study cohort, we conducted a case–control study of 265 postmenopausal breast cancer cases and 343 controls with prediagnostic mammograms and blood samples. Plasma was assayed for oestradiol, testosterone and sex hormone-binding globulin (SHBG) concentrations and mammographic density assessed by Cumulus.

Results:

Oestradiol and testosterone were negatively and SHBG positively associated with percentage density and absolute dense area, but after adjusting for body mass index the associations remained significant only for SHBG. Breast cancer risk was independently and significantly positively associated with percentage density (P=0.002), oestradiol (P=0.002) and testosterone (P=0.007) levels. Women in the highest tertile of both density and sex hormone level were at greatest risk, with an odds ratio of 7.81 (95% confidence interval (CI): 2.89–21.1) for oestradiol and 4.57 (95% CI: 1.75–11.9) for testosterone and high density compared with those who were in the lowest tertiles. The cumulative risk of breast cancer in the highest oestradiol and density tertiles, representing 8% of controls, was estimated as 12.8% at ages 50–69 years and 19.4% at ages 20–79 years, and in the lowest tertiles was 1.7% and 4.3%, respectively. Associations of breast cancer risk with tertiles of mammographic dense area were less strong than for percentage density.

Conclusions:

Endogenous sex hormone levels and mammographic density are independent risk factors for postmenopausal breast cancer, which in combination can identify women who might benefit from increased frequency of screening and chemoprophylaxis.     

Background risk of breast cancer influences the association between alcohol consumption and mammographic density

Background:

Alcohol consumption has been suggested to increase risk of breast cancer through a mechanism that also increases mammographic density. Whether the association between alcohol consumption and mammographic density is modified by background breast cancer risk has, however, not been studied.

Methods:

We conducted a population-based cross-sectional study of 53 060 Swedish women aged 40–74 years. Alcohol consumption was assessed using a web-based self-administered questionnaire. Mammographic density was measured using the fully-automated volumetric Volpara method. The Tyrer–Cuzick prediction model was used to estimate risk of developing breast cancer in the next 10 years. Linear regression models were used to evaluate the association between alcohol consumption and volumetric mammographic density and the potential influence of Tyrer–Cuzick breast cancer risk.

Results:

Overall, increasing alcohol consumption was associated with higher absolute dense volume (cm³) and per cent dense volume (%). The association between alcohol consumption and absolute dense volume was most pronounced among women with the highest (⩾5%) Tyrer–Cuzick 10-year risk. Among high-risk women, women consuming 5.0–9.9, 10.0–19.9, 20.0–29.9, and 30.0–40.0 g of alcohol per day had 2.6 cm³ (95% confidence interval (CI), 0.2–4.9), 2.9 cm³ (95% CI, −0.6 to 6.3), 4.6 cm³ (95% CI, 1.5–7.7), and 10.8 cm³ (95% CI, 4.8–17.0) higher absolute dense volume, respectively, as compared with women abstaining from alcohol. A trend of increasing alcohol consumption and higher absolute dense volume was seen in women at low (⩽3%) risk, but not in women at moderate (3.0–4.9%) risk.

Conclusion:

Alcohol consumption may increase breast cancer risk through increasing mammographic density, particularly in women at high background risk of breast cancer.     

Alcohol intake and endometrial cancer risk: a meta-analysis of prospective studies

Background:

Studies on alcohol intake in relation to endometrial cancer risk have produced inconsistent results.

Methods:

For a meta-analysis, we identified cohort studies of alcohol and endometrial cancer by a literature search of Pub-Med and Embase up to 1 March 2010 and by searching the reference lists of relevant articles.

Results:

Seven cohort studies, including 1 511 661 participants and 6086 endometrial cancer cases, were included in the dose–response random-effect meta-regression model. Compared with non-drinkers, women drinking less than 1 drink of alcohol (13 g of ethanol) per day had a lower risk for endometrial cancer; this risk was lower by 4% (95% confidence interval (95% CI): 0.93–1.00) for consumption up to 0.5 drink per day and by 7% (95% CI: 0.85–1.02) for consumption up to 1 drink. However, we found evidence of an increased risk for endometrial cancer for intakes higher than two alcoholic drinks per day: compared with non-drinkers, the risk was higher by 14% (95% CI: 0.95–1.36) for 2–2.5 drinks per day and by 25% (95% CI: 0.98–1.58) for >2.5 drinks per day.

Conclusion:

Our meta-analysis indicates a possible J-shaped relationship between alcohol intake and endometrial cancer risk.     

Supplemental folic acid in pregnancy and childhood cancer risk

Background:

We investigated the association between supplemental folic acid in pregnancy and childhood cancer in a nation-wide study of 687 406 live births in Norway, 1999–2010, and 799 children diagnosed later with cancer.

Methods:

Adjusted hazard ratios (HRs) compared cancer risk in children by approximated periconceptional folic acid levels (folic acid tablets and multivitamins (0.6 mg), only folic acid (0.4 mg), only multivitamins (0.2 mg)) and cancer risk in unexposed.

Results:

Any folic acid levels were not associated with leukemia (e.g., high-level folic acid HR 1.25; 95% CI 0.89–1.76, P_Trend 0.20), lymphoma (HR 0.96; 95% CI 0.42–2.21, P_Trend 0.51), central nervous system tumours (HR 0.68; 95% CI 0.42–1.10, P_Trend 0.32), neuroblastoma (HR 1.05; 95% CI 0.53–2.06, P_Trend 0.85), Wilms'' tumour (HR 1.16; 95% CI 0.52–2.58, P_Trend 0.76), or soft-tissue tumours (HR 0.77; 95% CI 0.34–1.75, P_Trend 0.90).

Conclusions:

Folic acid supplementation was not associated with risk of major childhood cancers.     

Association between diabetes,diabetes treatment and risk of developing endometrial cancer

Background:

A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women''s Health Initiative (WHI).

Methods:

A total of 88 107 postmenopausal women aged 50–79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.

Results:

Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13–1.85 for diabetes, HR=1.57, 95% CI: 1.19–2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08–1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.

Conclusions:

Our results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains.     

Vitamin C intake and breast cancer mortality in a cohort of Swedish women

Background:

Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied.

Methods:

Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort.

Results:

From 1987–2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57–0.99) compared with those in the lowest quartile (P_trend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR=0.84; 95% CI=0.71–1.00; P_trend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (≈1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52–2.17).

Conclusion:

Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.     

Concordance of National Cancer Registration with self-reported breast,bowel and lung cancer in England and Wales: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening

Background:

It has been suggested that lower UK cancer survival may be due to incomplete case ascertainment by cancer registries.

Methods:

We assessed concordance between self-reported breast, bowel and lung cancer and cancer registration (CR) for 1995–2007 in England and Wales in the UK Collaborative Trial of Ovarian Cancer Screening.

Results:

Concordance of breast cancer CR was higher (94.7%:95% CI: 94.1–95.3%) than for bowel (85.1%:95% CI: 82.1–87.8%) and lung (85.4%:95% CI: 76.3–92.0%). CR concordance was lower in breast cancer (94.5% vs 98.8%) survivors compared with deceased but the difference was small. No difference was found for bowel (85.3% vs 94.6%) or lung (87.1% vs 90.5%) cancer.

Conclusion:

Concordance of CR and self-reported cancer is high. Incomplete registration is unlikely to be a major cause of lower UK survival rates.     

Association of tamoxifen use and increased diabetes among Asian women diagnosed with breast cancer

Background:

We conducted a population-based cohort study to assess whether tamoxifen treatment is associated with an increased incidence of diabetes.

Methods:

Data obtained from the Taiwanese National Health Insurance Research Database were used for a population-based cohort study. The study cohort included 22 257 breast cancer patients diagnosed between 1 January 2000 and 31 December 2004. Among them, 15 210 cases received tamoxifen treatment and 7047 did not. Four subjects without breast cancer were frequency-matched by age and index year as the control group. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazards regression analysis.

Results:

Breast cancer patients exhibited a 14% higher rate of developing diabetes (adjusted HR=1.14, 95% CI=1.08–1.20) compared with non-breast cancer controls, but the significant difference was limited to tamoxifen users. In addition, tamoxifen users exhibited a significantly increased risk of diabetes compared with non-tamoxifen users among women diagnosed with breast cancer (adjusted HR=1.31, 95% CI=1.19–1.45). Stratification by age groups indicated that both younger and older women diagnosed with breast cancer exhibited a significantly higher risk of diabetes than the normal control subjects did, and tamoxifen users consistently exhibited a significantly higher diabetes risk than non-tamoxifen users or normal control subjects did, regardless of age. Both recent and remote uses of tamoxifen were associated with an increased likelihood of diabetes.

Conclusions:

The results of this population-based cohort study suggested that tamoxifen use in breast cancer patients might increase subsequent diabetes risk. The underlying mechanism remains unclear and further larger studies are mandatory to validate our findings.     

Leg length, sitting height and postmenopausal breast cancer risk

Background:

Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height.

Methods:

From the prospective Danish cohort ‘Diet, Cancer and Health'', 23 864 postmenopausal women enrolled during 1993–1997 were followed for a diagnosis of breast cancer in the Danish Cancer Registry through 2009.

Results:

The incidence rate ratios for breast cancer were 1.11 (95% CI=1.06–1.16) for each 5 cm increase in total height and 1.09 (95% CI=1.01–1.17) and 1.14 (95% CI=1.04–1.25) for each 5 cm increase in leg length and sitting height, respectively. There was no statistical significant difference between the associations for leg length and sitting height (P=0.47).

Conclusion:

Leg length does not seem to be more strongly associated with breast cancer among postmenopausal women than sitting height.     

Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-α-negative breast cancer

Background:

Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation.

Purpose:

To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer.

Methods

Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point.

Results:

In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR)=0.34; 95% confidence interval (CI)=0.14–0.81; P=0.015), whereas the opposite was seen in the AR− group (HR=2.92; 95% CI=1.16–7.31; P=0.022). Interaction test was significant P<0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR=0.12; 95% CI=0.014–0.95 P=0.044), whereas patients with AR− tumours had worse outcome when treated with tamoxifen (HR=3.98; 95% CI=1.32–12.03; P=0.014). Interaction test was significant P=0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression.

Conclusions:

AR can predict tamoxifen treatment benefit in patients with ER− tumours and triple-negative breast cancer.