Risk of breast cancer in relation to dietary intake of selenium and serum selenium as a marker of dietary intake: a prospective cohort study within The Malmö Diet and Cancer Study

Purpose

Selenium has been suggested to be protective against breast cancer, but the evidence remains inconclusive. Hence, it is important to further examine the potential protective effect. This prospective cohort study investigates pre-diagnostic selenium intake in relation to breast cancer risk. In addition, we analyze serum selenium as a marker of dietary intake.

Methods

This study includes 17,035 women in the Malmö Diet and Cancer cohort. Dietary assessment and serum samples were collected at baseline (1991–1996). During 344,584 person-years of follow-up, 1,427 incident cases were retrieved. Cox regression analysis examined breast cancer risks adjusted for potential confounding factors. In addition, odds ratios (ORs) were estimated for 1186 cases and an equal number of controls in relation to quartiles (Q) of selenium intake and groups consisting of a combination of intake and serum selenium levels.

Results

No overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk was found. The adjusted relative risk for breast cancer in selenium intake Q4 versus Q1 was 0.96 (0.83–1.12) (P_trend?=?0.65). Similarly, adjusted the OR for breast cancer in selenium intake for Q4 versus Q1 was 0.97 (0.76–1.23). The kappa value, 0.096 (p?=?0.001), showed poor agreement between serum selenium and selenium intake.

Conclusion

Our findings suggest that there is no overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk. Finally, our results showed a poor correlation between estimated selenium intake and serum selenium.

     

A prospective study of adiposity and postmenopausal breast cancer risk: the Malmö Diet and Cancer Study

High BMI is a well-known risk factor for postmenopausal breast cancer. There have been some reports of excess risk in association with weight gain and WHR, but little is known about the influence of body fatness per se. Using data from the Malm? Diet and Cancer Study, a prospective cohort study, 12,159 postmenopausal women (59.9 +/- 7.7 years) were categorized by quintiles of baseline anthropometric and impedance measures and reported weight change since age 20. RRs from multivariate Cox regression models were calculated. All analyses were adjusted for age, height, smoking, alcohol consumption, occupation, marital status, parity, age at first pregnancy, age at menarche and current hormone use. During the 5.7 years of follow-up, there were 246 incident breast cancer cases. Weight, height, BMI and %BF were positively associated with risk of breast cancer (p(trend) 21 kg (top quintile) had an RR of 1.75 (95% CI 1.11-2.77) compared to women with low weight gain. Breast cancer risk in postmenopausal women is predicted by increased body fat and weight gain. %BF is a more discriminating risk factor for breast cancer incidence than the commonly used BMI.     

High fat and alcohol intakes are risk factors of postmenopausal breast cancer: a prospective study from the Malmö diet and cancer cohort

Associations between intakes of relative fat, total alcohol and alcoholic beverages and risk of breast cancer were examined in a subsample of 11726 postmenopausal women from the MDC cohort. The MDC conducted baseline examinations from 1991 to 1996; the end of follow-up was 31 December 2001. Data were obtained by an interview-based diet history method, a structured questionnaire, anthropometric measurements and national and regional cancer registries. During 89602 person-years of follow-up, 342 incident cases were documented. Cox regression analysis examined breast cancer risks adjusted for potential confounders. Two energy-adjustment approaches (i.e., adjusting for total energy vs. adjusting for nonalcohol energy) were used. High total alcohol intake was associated with a nonsignificantly elevated risk. High wine intake was associated with a significantly elevated breast cancer risk (relative risk = 2.12, 95% CI 1.24-3.60). There were significant trends of increased breast cancer risk across quintiles of relative fat intake. Mutual adjustment did not affect risk estimates for total alcohol or relative fat intakes. The specific energy-adjustment approach did not influence associations differentially.     

Intakes of plant foods, fibre and fat and risk of breast cancer--a prospective study in the Malmö Diet and Cancer cohort

The objective of this study was to investigate prospectively the associations between intakes of plant foods, fibre and relative fat and risk of breast cancer in a subsample of 11 726 postmenopausal women in the Malm? Diet and Cancer cohort. Data were obtained by an interview-based diet history method, a structured questionnaire, anthropometrical measurements and national and regional cancer registries. During 89 602 person-years of follow-up, 342 incident cases were documented. Cox regression analysis examined breast cancer risks adjusted for potential confounders. High fibre intakes were associated with a lower risk of postmenopausal breast cancer, incidence rate ratio=0.58, 95% CI: 0.40, 0.84, for the highest quintile of fibre intake compared to the lowest quintile. The combination high fibre-low fat had the lowest risk when examining the effect in each cell of cross-classified tertiles of fibre and fat intakes. An interaction (P=0.049) was found between fibre- and fat-tertiles. There was no significant association between breast cancer risk and intakes of any of the plant food subgroups. These findings support the hypothesis that a dietary pattern characterised by high fibre and low fat intakes is associated with a lower risk of postmenopausal breast cancer.     

A prospective study of angiogenic markers and postmenopausal breast cancer risk in the prostate,lung, colorectal,and ovarian cancer screening trial

Purpose

Pro-angiogenic factors are positively associated with breast tumor staging and poorer prognosis, but their role in the etiology of breast cancer has not been assessed.

Methods

We measured serum levels of the pro-angiogenic vascular endothelial growth factor A (VEGF), and placental growth factor (PlGF) and anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) in 352 incident breast cancer cases [mean age at diagnosis 67 (range 55–83)] and 352 non-cases in the prostate, lung, colorectal, and ovarian screening trial (women enrolled 1993–2001, followed through 2005) matched on age and date of enrollment. Cases were followed on average 4.2 years from blood draw to diagnosis, range 3.9–12.8 years; 53 % were estrogen receptor positive/progesterone receptor positive (ER+/PR+), and 13 % were ER?/PR?. Quartile-specific hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using weighted Cox proportional hazards regression models adjusted for known breast cancer risk factors. An ordinal variable for the angiogenic markers was used to test for trend in the HR.

Results

Comparing the highest to lowest quartile, multivariable HR were 0.90 for VEGF (95 % CI 0.33–2.43, p trend = 0.88), 1.38 for sFlt-1 (95 % CI 0.63–3.04, p trend = 0.63), and 0.62 for PlGF (95 % CI 0.19–2.00, p trend = 0.73). Risk patterns were not altered when all angiogenic markers were included in the model simultaneously, or by restricting analyses to invasive breast cancers, to cases diagnosed two or more years after blood collection or to ER+ tumors.

Conclusions

There was no evidence of an increased breast cancer risk associated with circulating levels of pro-angiogenic markers VEGF and PlGF or a reduced risk with circulating levels of anti-angiogenic marker sFlt-1.

     

Diverging breast cancer mortality rates in relation to screening? A comparison of Nijmegen to Arnhem and the Netherlands, 1969-1997

Age-standardised breast cancer mortality rates have been stable for decades. However, rates have started to decline in several Western countries. In countries where population-based screening programmes for breast cancer were introduced in the late 1980s or early 1990s, the key question now is to what extent screening is responsible for the reported declines in mortality. This study compares breast cancer mortality rates in Nijmegen, where a screening programme for breast cancer was introduced in 1975, to a control city, Arnhem, and to the Netherlands as a whole over a 20-year period. Age-standardised breast cancer mortality rates as well as age-standardised mortality ratios were calculated for successive calendar years from 1969 to 1997. Further, a tailor-made period-cohort-group Poisson regression model was fitted. Figures displaying age-standardised mortality rates and ratios showed inconclusive patterns with regard to the expected impact of screening. Depending on when mortality rates were allowed to deviate between populations, the period-cohort-group analysis indicated a non-significant 6% to 16% reduction in breast cancer mortality after 2 decades in favour of the Nijmegen female population. Possible explanations are discussed as to why the mortality reductions reported by randomised trials might not be observed in a public health screening programme, such as the Nijmegen programme, evaluated by comparisons of geographical trends.     

Does famotidine enhance tumor infiltrating lymphocytes in breast cancer? Results of a randomized prospective pilot study

Thirty patients with breast cancer were prospectively randomized into case and control groups receiving 40 mg famotidine preoperatively for 10-14 days and routine premedication, respectively. Surgical specimens were evaluated objectively for tumor infiltrating lymphocytes in the center and in the periphery of the tumor along with evaluation of metastatic lymph nodes for reactive changes. Ten famotidine-treated cases (67%) showed significant lymphocytic infiltration in the center compared to 4 controls (27%) (p = 0.03). Eleven cases (77%) had significant lymphocytic infiltration in the periphery (p = 0.03) compared to 5 controls (33%). Considering both sites, lymphocytic response was significant in 9 (60%) cases as opposed to only 3 (20%) controls (p = 0.03). This response did not correlate with the stage, grade of tumor or menopausal status of patients in either group. Seventy-eight percent (78%) of the cases showed significant reactive changes in the metastatic lymph nodes as compared to 22% in controls (p < 0.01). This study suggests that famotidine enhances tumor infiltrating lymphocytes in breast cancer and might have potential as an immunomodulator. A larger confirmatory study is suggested.     

Impact of autonomic and self-regulation on cancer-related fatigue and distress in breast cancer patients – a prospective observational study

Purpose

Cancer-related fatigue (CRF) has a major impact on the quality of life in breast cancer patients (BC). So far, only a few prospective studies have investigated the effect of adaptive salutogenic mechanisms on CRF. The aim of our study was to evaluate the possible prospective influence of autonomic Regulation (aR) and self-regulation (SR) on CRF and distress in long-term survivors.

Methods

95 BC and 80 healthy female controls (C) had been included in the observational study between 2000 and 2001 and completed the questionnaires on aR, SR and Hospital Anxiety and Depression Scale (HADS). Of these, 62 BC, and 58 C participated in the re-evaluation 6.6 years later: 16 participants were deceased (14 BC and 2 C). During follow-up, participants were requested to answer questions involving (Cancer Fatigue Scales) CFS-D, aR, SR and HADS. Multiple regression analysis was used to evaluate the influence of aR, SR, age, Charlson co-morbidity-index and diagnosis on CFS-D and HADS, and to select further potentially relevant factors.

Results

High aR values showed significant effects, namely inverse relationships with CFS-D, cognitive fatigue, anxiety and depression. SR showed a reduced influence on anxiety and depression (all p?<?0.05).

Conclusions

Autonomic regulation might have an independent, reductive influence on global fatigue, cognitive fatigue and – together with self-regulation – it seems to have a protective influence on anxiety and depression. The connection between these parameters is still unclear and awaits further evaluation.

Implication for Cancer Survivors

AR seems to be a prognostic factor in breast cancer survivors, capable of reducing cancer-related fatigue and self-regulation distress as well. Further research is necessary in order to show how aR can be improved by therapeutic interventions.     

Second to fourth digit ratio (2D?:?4D), breast cancer risk factors,and breast cancer risk: a prospective cohort study

Background:

We aimed to assess whether 2D : 4D measures are associated with breast cancer risk.

Methods:

We derived the ratio of the lengths of the index and ring fingers (2D : 4D), and right minus left 2D : 4D (Δ_r−l) from digit lengths measured from photocopies of participants'' hands collected during a recent follow-up of the Melbourne Collaborative Cohort Study, a prospective study including 24 469 women. Of the 9044 women with available data, we identified 573 incident breast cancer cases. Hazard ratios (HR) and 95% confidence intervals (CI) for a one standard deviation difference in 2D : 4D measures were obtained from Weibull survival models, and linear regression models were used to examine potential associations between 2D : 4D measures and age at menarche and menopause.

Results:

We found a direct association between left 2D : 4D and breast cancer risk, an inverse association between Δ_r−l and risk of breast cancer, but no association between right 2D : 4D and breast cancer risk. Among breast cancer cases, both right 2D : 4D and Δ_r−l were inversely associated with age at diagnosis. We also observed associations between both right 2D : 4D and Δ_r−l and age at menopause, with increasing digit ratio measures related to earlier mean age at menopause.

Conclusion:

Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer. If confirmed in other studies, this suggests that lower exposure or sensitivity to prenatal testosterone might be associated with lower risk of breast cancer.     

Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

Background  

Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer.     

Partial breast irradiation for locally recurrent breast cancer within a second breast conserving treatment: Alternative to mastectomy? Results from a prospective trial

Purpose

To assess the outcome of multi-catheter pulse dose rate (PDR) brachytherapy of re-irradiation for local ipsilateral breast tumour recurrence (IBTR) in regard to local control, survival, morbidity and quality of life (QoL).

Patients and methods

Between 1999 and 2006, 39 patients were included with histologically confirmed IBTR, Karnofsky index ?80% and refusal of mastectomy. Exclusion criteria were multicentric invasive growth pattern, unclear surgical margins, distant metastasis and a postoperative breast not suitable for interstitial brachytherapy. Primary endpoint was local tumour control. Morbidity, cosmetic outcome and QoL were assessed in 24/39 patients.

Results

The five year actuarial local control rate was 93% after a mean follow up of 57 (±30) months with two second local relapses. Overall survival and disease free survival, both at 5 years, were 87% and 77%, respectively. Late side effects Grade 1-2 were observed in 20/24 patients after a mean follow-up of 30 (±18) months. Late side effects ?Grade 3 occurred in 4/24 patients. Cosmetic outcome was excellent to fair in 76% of women. Overall QoL was comparable to a healthy control group. Mean scores of scales and items of QLQ-BR23 were comparable to primary breast conserving therapy.

Conclusions

Accelerated PDR-brachytherapy following breast conserving surgery (BCS) for local IBTR results in local tumour control comparable to mastectomy. Morbidity is moderate; the cosmetic outcome is good and hardly any impairment on QoL is observed.     

Effects of toremifene and anastrozole on serum lipids and bone metabolism in postmenopausal females with estrogen receptor–positive breast cancer: the results of a 2-year multicenter open randomized study

The potential long-term adverse effects on quality of life have to be considered when selecting agents for adjuvant hormonal treatment for postmenopausal patients with estrogen receptor–positive breast cancer. We performed a 2-year multicenter randomized study to assess the differences in the time course effects between toremifene (TOR) and anastrozole (ANA) on serum lipid profiles and bone metabolism. This study assessed the serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (Apo A1), and apolipoprotein B (Apo B) as lipid profiles and bone-specific alkaline phosphatase (BAP) and the N-telopeptide of type-I collagen (NTX) as bone turnover markers in patients who received daily doses of 40 mg and 1 mg for TOR and ANA, respectively. A decreased serum level of TC, LDL-C, and Apo B was, respectively, observed at 6 months in 6.2, 12.9, and 13.8% of the patients who received TOR compared with the baseline. These decreases were maintained for at least 24 months. These lipid levels were not changed in those who received ANA. In the TOR patients, there was an increase in the serum level of HDL-C and Apo A1 at 6 months in 17.1 and 16.3%, respectively, which was maintained for at least 24 months, whereas these levels were almost stable in the patients who received ANA. Serum BAP decreased by 12.1% at 12 months and further decreased at 24 months and the serum NTX decreased by 22.0% at 6 months, which was maintained for at least 24 months in the patients who received TOR. In contrast, the serum BAP was increased by 26.0% at 6 months and by 29.2% at 12 months and the serum NTX increased by 21.3% at 24 months compared with baseline in those received ANA. However, the serum BAP increase was not significant at 24 months. TOR provides better effects than ANA in terms of lipid profiles and bone metabolism in postmenopausal females with early breast cancer.     

Consumption of dairy and meat in relation to breast cancer risk in the Black Women’s Health Study

Purpose

Dairy and meat consumption may impact breast cancer risk through modification of hormones (e.g., estrogen), through specific nutrients (e.g., vitamin D), or through products formed in processing/cooking (e.g., heterocyclic amines). Results relating meat and dairy intake to breast cancer risk have been conflicting. Thus, we examined the risk of breast cancer in relation to intake of dairy and meat in a large prospective cohort study.

Methods

In the Black Women’s Health Study, 1,268 incident breast cancer cases were identified among 52,062 women during 12 years of follow-up. Multivariable (MV) relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using Cox proportional hazards models.

Results

Null associations were observed for total milk (MV RR = 1.05, 95 % CI 0.74–1.46 comparing ≥1,000–0 g/week) and total meat (MV RR = 1.04, 95 % CI 0.85–1.28 comparing ≥1,000 < 400 g/week) intake and risk of breast cancer. Associations with intakes of specific types of dairy, specific types of meat, and dietary calcium and vitamin D were also null. The associations were not modified by reproductive (e.g., parity) or lifestyle factors (e.g., smoking). Associations with estrogen receptor (ER) positive (+), ER negative (?), progesterone receptor (PR) +, PR?, ER+/PR+, and ER?/PR? breast cancer were generally null.

Conclusions

This analysis of African-American women provides little support for associations of dairy and meat intake with breast cancer risk.     

Tea and coffee intake in relation to risk of breast cancer in the Black Women’s Health Study

Objective

Prospective studies of tea and coffee intake and breast cancer risk have yielded inconsistent results. None of these studies has reported separately on African-American women. We prospectively examined the relation of tea and coffee consumption to risk of breast cancer among 52,062 women aged 21–69 at enrollment in 1995 in the Black Women’s Health Study.

Methods

Dietary intake was assessed in 1995 and 2001 using a validated food frequency questionnaire. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI), adjusted for breast cancer risk factors.

Results

During 12 years of follow-up through 2007, there were 1,268 incident cases of breast cancer. Intakes of tea, coffee, and caffeine were not significantly associated with the risk of breast cancer overall. The IRRs for consumption of ≥4 cups/day compared with none were 1.13 (95% CI 0.78–1.63) for tea and 1.03 (95% CI 0.77–1.39) for caffeinated coffee, and the IRR for the top quintile relative to the bottom quintile of caffeine intake was 1.04 (95% CI 0.87–1.24). Consumption of tea, coffee, and caffeine was not significantly associated with breast cancer risk according to menopausal status or hormone receptor status.

Conclusion

Our findings suggest that intakes of tea, coffee, and caffeine are not associated with the risk of breast cancer among African-American women.     

HER2. a 'predictive factor' ready to use in the daily management of breast cancer patients?

The past few years have witnessed an exponential increase in studies trying to identify molecular markers in patients with breast tumours that might predict for the success or failure of hormonal therapy or chemotherapy. HER2, a tyrosine kinase membrane receptor of the epidermal growth factor receptor family, has been the most widely studied marker in this respect. This paper attempts to critically review to what extent HER2 may improve 'treatment individualisation' for the breast cancer patient.     

Anthropometric factors, physical activity, and breast cancer risk in relation to hormone receptor and menopausal status in Japanese women: a case–control study

Purpose

The associations between anthropometric factors, physical activity (PA), and breast cancer risk in terms of estrogen-receptor/progesterone-receptor (ER/PgR) status have been unclear in Japanese women. This case–control study was designed to evaluate these associations.

Methods

From among female patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2009, 1,017 breast cancer cases (538ER+/PgR+, 125ER+/PgR?, 23 ER?/PgR+, 249 ER?/PgR?, and 82 missing) and 2,902 controls were selected. Height, weight, body mass index (BMI) (kg/m²), and time spent exercising (hours/week) were assessed using a self-administered questionnaire. Polytomous logistic regression analysis and tests for heterogeneity across ER+/PgR+ and ER?/PgR? were conducted.

Results

Higher BMI was associated with a higher risk of ER+/PgR+ cancer among women overall [odds ratio (OR) = 2.41, 95 % confidence interval (CI) 1.37–4.23 for BMI ≥30.0; P _trend = 0.0001] and postmenopausal women (OR = 6.24, 95 % CI 2.68–14.53 for BMI ≥30.0; P _trend < 0.0001). A longer time spent exercising (more than 5 h/week) showed a decreased risk for any type of breast cancer among overall and pre- and postmenopausal women, although this did not reach statistical significance. Height was not associated with any risk.

Conclusions

Higher BMI is associated with an increased risk of ER+/PgR+ cancer among women overall and postmenopausal women. PA might be associated with a decreased risk of any type. To prevent breast cancer, weight control and PA are important.     

Dietary patterns and the risk of postmenopausal breast cancer in a German case–control study

Objective  

Dietary patterns have been inconsistently associated with breast cancer risk. We assessed dietary patterns in association with postmenopausal breast cancer risk using an exploratory approach.     

Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case–control study in Thai women

Dietary folate as well as polymorphic variants in one-carbon metabolism genes may modulate risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and repair. Alcohol is well recognized as a risk factor for breast cancer, and interactions with one-carbon metabolism has also been suggested. The purpose of this study is to test the hypothesis that genetic polymorphisms in the folate and alcohol metabolic pathway are associated with breast cancer risk. Twenty-seven single nucleotide polymorphisms (SNPs) in the MTR, MTRR, MTHFR, TYMS, ADH1C, ALDH2, GSTP1, NAT1, NAT2, CYP2E1 DRD2, DRD3, and SLC6A4 were genotyped. Five hundred and seventy patients with histopathogically confirmed breast cancer and 497 controls were included in the present study. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95% CI). Increased risk was observed for homozygotes at the MTR SNPs (rs1770449 and rs1050993) with the OR = 2.21 (95% CI 1.18–4.16) and OR = 2.24 (95% CI 1.19–4.22), respectively. A stratified analysis by menopausal status indicated the association between the NAT2 SNP (rs1799930) and breast cancer was mainly evident in premenopausal women (OR 2.70, 95% CI 1.20–6.07), while the MTRR SNP (rs162049) was significant in postmenopausal women (OR 1.61, 95% CI 1.07–2.44). Furthermore, SNPs of the genes that contribute to alcohol behavior, DRD3 (rs167770), DRD2 (rs10891556), and SLC6A4 (rs140701), were also associated with an increased risk of breast cancer. No gene–gene or gene–environment interactions were observed in this study. Our results suggest that genetic polymorphisms in folate and alcohol metabolic pathway influence the risk of breast cancer in Thai population.