Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study

Introduction

Phytoestrogens are a group of compounds found in plants that structurally resemble the hormone oestradiol, and thus have the potential to act as oestrogen agonists or antagonists. Their potential effects may alter the risk of breast cancer, but only a limited range of phytoestrogens has been examined in prospective cohort studies.

Methods

Serum and urine samples from 237 incident breast cancer cases and 952 control individuals (aged 45 to 75 years) in the European Prospective into Cancer-Norfolk cohort were analysed for seven phytoestrogens (daidzein, enterodiol, enterolactone, genistein, glycitein, o-desmethylangolensin, and equol) using liquid chromatography/mass spectrometry. Data on participants' diet, demographics, anthropometrics, and medical history were collected upon recruitment. All models were adjusted for weight, fat and energy intake, family history of breast cancer, social class, analytical batch, and factors related to oestrogen exposure.

Results

Urinary or serum phytoestrogens were not associated with protection from breast cancer in the European Prospective into Cancer-Norfolk cohort. Breast cancer risk was marginally increased with higher levels of total urinary isoflavones (odds ratio = 1.08 (95% confidence interval = 1.00 to 1.16), P = 0.055); among those with oestrogen receptor-positive tumours, the risk of breast cancer was increased with higher levels of urinary equol (odds ratio = 1.07 (95% confidence interval = 1.01 to 1.12), P = 0.013).

Conclusion

There was limited evidence of an association between phytoestrogen biomarkers and breast cancer risk in the present study. There was no indication of decreased likelihood of breast cancer with higher levels of phytoestrogen biomarkers, but the observation that some phytoestrogen biomarkers may be associated with greater risk of breast cancer warrants further study with greater statistical power.     

Alcohol intake,drinking patterns and risk of postmenopausal breast cancer in Denmark: a prospective cohort study

Objective: The available epidemiological evidence indicates that drinking alcohol per se is associated with breast cancer. However, it has not been investigated how the breast cancer risk for a given total alcohol consumption depends on the drinking frequency. Methods: Within the prospective study on Diet, Cancer and Health, we examined the relationship between breast cancer, intake of total alcohol and frequency of drinking among 23,778 postmenopausal women, among whom 425 cases of breast cancer accrued during a median follow-up of 4.8 years. Results: The dose–response relationship between total alcohol intake and breast cancer showed an increase in the rate ratio of 1.10 per 10 g/day (95% CI: 1.04–1.16) with no evidence for differences by type of alcohol beverage. No interaction was found between drinking frequency and total alcohol intake in the risk of breast cancer (p = 0.40). Conclusions: The present study supports previous ones in showing a monotonic increase in the risk of breast cancer among postmenopausal women with increasing average daily intake of alcohol, and this relationship with alcohol intake did not depend on drinking frequency.     

Estrogen-progestin replacement therapy and breast cancer risk: the Women's Health Study (United States)

Objective: While there is substantial evidence that unopposed estrogen use increases the risk of breast cancer, there are limited data from epidemiologic studies on the impact of estrogen–progestin combinations. We therefore examined estrogen–progestin replacement therapy and breast cancer risk in the Women's Health Study. Methods: We investigated postmenopausal hormone (PMH) use among 17,835 apparently healthy postmenopausal women aged 45 years, and followed them prospectively for an average of 5.9 years. Breast cancer occurred in 411 women. Results: The multivariate relative risks of all breast cancer associated with never use of PMH, use of estrogen replacement therapy (ERT), and use of estrogen–progestin replacement therapy (HRT) were 1.00 (referent), 0.96 (95% CI 0.65–1.42), and 1.37 (95% CI 1.05–1.78). The increase in risk among users of HRT was largely limited to those women who had used estrogen–progestin replacement therapy for five years or more, and to those women who were on continuous rather than cyclic progestin combinations. Higher doses of estrogen, but not progestin, were associated with increased breast cancer risk, compared with lower doses. Conclusions: These prospective data suggest that use of estrogen–progestin replacement therapy imparts an increased risk of breast cancer in comparison with never use of PMH.     

Effects of mammographic density and benign breast disease on breast cancer risk (United States)

Background: Having either a history of benign breast disease, particularly atypical hyperplasia or extensive mammographic breast density, is associated with increased breast cancer risk. Previous studies have described an association between benign breast disease histology and breast density. However, whether these features measure the same risk, or are independent risk factors, has not been addressed. Methods: This case–control study, nested within the prospective follow-up of the Breast Cancer Detection Demonstration Project, evaluated both benign histologic and mammographic density information from 347 women who later developed breast cancer and 410 age- and race-matched controls without breast cancer. Multivariate logistic regression analyses provided maximum-likelihood estimates of the odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relative risk of breast cancer associated with each exposure. Results: Adjusting for mammographic density, the OR for atypical hyperplasia was 2.1 (95% CI: 1.3–3.6), and adjusting for benign breast histology, the OR for 75% density was 3.8 (95% CI: 2.0–7.2). Women with nonproliferative benign breast disease and 75% density had an OR of 5.8 (95% CI: 1.8–18.6), and women with <50% density and atypical hyperplasia had an OR of 4.1 (95% CI: 2.1–8.0). Conclusions: In this study, both benign breast disease histology and the percentage of the breast area with mammographic density were associated with breast cancer risk. However, women with both proliferative benign breast disease and 75% density were not at as high a risk of breast cancer due to the combination of effects (p = 0.002) as women with only one of these factors.     

Sources of Phytoestrogen Exposure among Non-Asian Women in California, USA

Objective: We recently described the development of a comprehensive database for assessing phytoestrogen exposure in epidemiologic studies [1]. This paper describes the first application of this database and the primary sources of phytoestrogen consumption in non-Asian women. Methods: Four hundred and forty-seven randomly selected African-American, Latina, and white women, ages 50 79 years, residing in California's San Francisco Bay Area and participating as controls in an ongoing population-based case-control study of breast cancer, were included in the present analysis. Average daily consumption of each of seven phytoestrogenic compounds was determined for each woman by combining the values from the new database with food consumption reported on a food-frequency questionnaire. Results: Phytoestrogens in the non-Asian Bay Area diet appear to come primarily from: (1) traditional soy-based foods (e.g. tofu and soy milk); (2) "hidden" sources of soy (e.g. foods containing added soy protein is concentrate, or soy flour, e.g. many brands of doughnuts and white bread); and (3) a variety of foods which contain only low to moderate amounts of phytoestrogens per 100 grams but which are frequently consumed (e.g. coffee and orange juice). Conclusions: In the absence of a comprehensive assessment of various phytoestrogens in a wide variety of foods, epidemiologic studies could suffer from the effects of uncontrolled confounding by unmeasured sources of phytoestrogen exposure potentially leading to biased estimates of effect and misinterpretation of findings.     

Menstrual risk factors and early-onset breast cancer

Objectives: Epidemiologic studies provide evidence for increased breast cancer risk among women with prolonged exposure to endogenous estrogens and progesterone. Menstrual cycle characteristics, such as early menarche, rapid initiation of regular ovulatory cycles, short cycle length, and more days of flow, all potentially contribute to higher cumulative ovarian hormone exposure. Methods: We assessed the associations between these characteristics and breast cancer risk in a population-based, case–control study of 1505 controls and 1647 newly diagnosed cases, all younger than 45 years of age. Results: Compared to women with menarche at 15 years, we observed some increase in risk for women with younger ages at menarche, although those with very early ages were not at particularly high risk [odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1–1.9 for menarche at age 12 and OR = 1.2, 95% CI = 0.9–1.7 for menarche at age 10]. Women who reported having regular menstrual cycles within 2 years of menarche were at increased breast cancer risk (OR = 1.7, 95% CI = 1.2–2.3), compared to those never having regular cycles. Stratification by current body mass index revealed slightly stronger associations with menstrual characteristics among thinner women ( < 22.0 kg/m²) compared to heavier women ( > 28.8 kg/m²). Conclusions: These findings suggest that future studies should focus on clarifying how the interrelated effects of body size and menstrual factors, such as age at menarche and cycle regularity, contribute to breast cancer etiology.     

Repeated measurements of organochlorine exposure and breast cancer risk (Denmark)

Objective: To prospectively evaluate if repeated measurements of organochlorine exposure provide a more precise measure of breast cancer risk. Methods: In the Copenhagen City Heart Study (CCHS) participants donated blood twice, in 1976–1978 and 1981–1983. Information on breast cancer risk factors was obtained through standardized questionnaires. A cohort nested case–control study of 155 cases and 274 matched breast cancer-free controls who had participated in both CCHS examinations was conducted. The average serum organochlorine concentration over the course of the two examinations was used, testing a possible association between organochlorine exposure and breast cancer risk. Results: A high serum concentration of p,p-DDT over the course of the two examinations was associated with a more than three-fold significantly increased risk of breast cancer, and a dose–response relationship was apparent. Furthermore, the risk of breast cancer increased with increasing serum concentrations of PCB congener 118 and 138 and the total amount of DDT isomers (DDT), but the trends were not significant. Conclusion: This study provides new evidence of the adverse effect of some organochlorines on breast cancer risk. Furthermore, repeated assessment of exposure during a relevant time period may provide a more precise risk estimate than a single measurement.     

Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis

Background:

Many epidemiological studies have investigated the association between folate intake, circulating folate level and risk of breast cancer; however, the findings were inconsistent between the studies.

Methods:

We searched the PubMed and MEDLINE databases updated to January, 2014 and performed the systematic review and meta-analysis of the published epidemiological studies to assess the associations between folate intake level, circulating folate level and the overall risk of breast cancer.

Results:

In all, 16 eligible prospective studies with a total of 744 068 participants and 26 205 breast cancer patients and 26 case–control studies with a total of 16 826 cases and 21 820 controls that have evaluated the association between folate intake and breast cancer risk were identified. Pooled analysis of the prospective studies and case–control studies suggested a potential nonlinearity relationship for dietary folate intake and breast cancer risk. Prospective studies indicated a U-shaped relationship for the dietary folate intake and breast cancer risk. Women with daily dietary folate intake between 153 and 400 μg showed a significant reduced breast cancer risk compared with those <153 μg, but not for those >400 μg. The case–control studies also suggested a significantly negative correlation between the dietary folate intake level and the breast cancer risk. Increased dietary folate intake reduced breast cancer risk for women with higher alcohol intake level, but not for those with lower alcohol intake. No significant association between circulating folate level and breast cancer risk was found when the results of 8 identified studies with 5924 participants were pooled.

Conclusions:

Our studies suggested that folate may have preventive effects against breast cancer risk, especially for those with higher alcohol consumption level; however, the dose and timing are critical and more studies are warranted to further elucidate the questions.     

Passive and active smoking and breast cancer risk in Canada, 1994–97

Background: Studies comparing ever smokers with never smokers have found little increase in breast cancer risk. However, the five published studies examining passive smoking and breast cancer have all suggested associations with both passive and active smoking, particularly premenopausal risk. Methods: We analyzed data collected through the Canadian National Enhanced Cancer Surveillance System, from 805 premenopausal and 1512 postmenopausal women with newly diagnosed (incident), histologically confirmed, primary breast cancer and 2438 population controls. The mailed questionnaire included questions on breast cancer risk factors and a lifetime residential and occupational history of exposure to passive smoking. Results: Among premenopausal women who were never active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer odds ratio (OR) of 2.3 (95% confidence interval [CI] 1.2–4.6). Passive exposure showed a strong dose–response trend (test for trend p=0.0007) with an OR of 2.9 (95% CI 1.3–6.6) for more than 35 years of passive residential and/or occupational exposure. When premenopausal women who had ever actively smoked were compared with women never regularly exposed to passive or active smoke, the adjusted OR for breast cancer was also 2.3 (95% CI 1.2–4.5). Among postmenopausal women who were never-active smokers, regular exposure to passive smoke was associated with an adjusted breast cancer OR of 1.2 (95% CI 0.8–1.8) and an OR of 1.4 (95% CI 0.9–2.3) for the most highly exposed quartile of women. The adjusted OR for postmenopausal breast cancer risk for ever-active smokers compared with women never regularly exposed to passive or active smoke was 1.5 (95% CI 1.0–2.3). Statistically significant dose–response relationships were observed with increasing years of smoking, increasing pack-years and decreasing years since quitting. Women with 35 or more years of smoking had an adjusted OR of 1.7 (95% CI 1.1–2.7). Conclusions: Active and passive smoking may be associated with increased breast cancer risk, particularly premenopausal risk.     

Genetic polymorphisms of <Emphasis Type="Italic">TGF-β</Emphasis>1 &; <Emphasis Type="Italic">TNF-β</Emphasis> and breast cancer risk

Objective. The proliferation of malignant breast epithelial cells is regulated by various stimuli including cytokines and growth factors, thus the variants of those genes may modify the breast cancer risk. To evaluate the potential influences of TGF-1 T²⁹C and TNF- A²⁵²G gene polymorphisms on breast cancer risk, a case–control study was conducted in Korea.Methods. Histologically confirmed breast cancer cases (n = 560) and controls (n=509) with no previous history of cancer were recruited from three teaching hospitals in Seoul, Korea. Genotypes were determined by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression model adjusting for age, body mass index, education, parity, age at first full-term pregnancy, and family history of breast cancer. Results. The TGF-1 ²⁹C-allele containing genotypes posed an increased risk of breast cancer (OR=1.3, 95% CI=1.02–1.79), especially in postmenopausal women (OR=1.6, 95% CI=1.01–2.44). Similarly, the TNF- ²⁵²G-allele containing genotypes posed an increased risk of postmenopausal breast cancer (OR=1.7, 95% CI=1.09–2.55). The risk of postmenopausal breast cancer increased in parallel with the number of the risk genotypes (p for trend <0.01). When data were stratified by the presumed non-genetic risk factors, TGF-1 C-allele containing genotypes were found to increase breast cancer risk almost two-fold in postmenopausal women with greater than median body mass index (>22.8 kg/m²) (OR=1.9, 95% CI=1.04–3.37).Conclusion. The results of this study therefore suggest that polymorphisms of TGF-1 and TNF- genes may modify individual susceptibility to breast cancer in Korean women.     

A cohort study of reproductive factors and family history of breast cancer in southern Sweden

Background. Studies have been contradictory regarding the hypothesis that reproductive risk factors of breast cancer as parity and age at first full-term pregnancy (AFFP) operate differently in women with and without a family history of breast cancer. Methods. The overall tumour incidence and breast cancer incidence related to fertility factors were followed in a population based cohort of 29,508 women aged 25–65 when interviewed between 1990 and 1992 in south Sweden. At the end of the follow up in December 1999, the cohort constituted 226,611 person years. The risk of breast cancer in relation to reproductive factors were studied in women with at least one first degree relative with breast cancer and compared with women without a family history. Findings. A total of 1145 malignant tumours were seen and 1166.6 were expected (SIR = 0.98, 95% CI = 0.93–1.04). Slightly more breast cancer cases were seen 434 than expected 387.69 (SIR = 1.12, 95% CI = 1.02–1.23). A family history of breast cancer among a first degree relative was present in 1615 women. Forty-five breast cancers were seen among these women while 24.27 was expectecd (SIR = 1.85, 95% CI = 1.35–2.48). Nulliparous women with a family history of breast cancer had a higher risk of breast cancer, SIR = 1.76, 95% CI = 0.64–3.82, compared with nulliparous women without a family history, SIR = 1.13, 95% CI 0.99–1.29. Similarly women with parity 1–2 with a family history had a higher SIR = 1.81, 95% CI = 1.16–2.69 compared with women without a family history having 1–2 children, SIR = 1.13, 95% CI = 0.99–1.29. In women with 3 children those with a family history continued to have a high SIR = 1.98, 95% CI = 1.11–3.27 compared with women without a family history SIR = 0.90, 95% CI = 0.73–1.09. An early full-term pregnancy was protective in both groups. A higher risk than nulliparous women were seen after age 25 in the family history group and after age 30 in the sporadic cancer group. Interpretation. Women with a first degree family history of breast cancer do not experience the same protection from a high number of pregnancies as women without a family history. However, an early first full-term pregnancy seems to offer a substantial protection in the family history group if undertaken before age 20. This suggest that reproductive factors tend to operate differently in the two groups of women.     

Microdissection and microcloning of chromosomal alterations in human breast cancer

Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.Presented by Jeffrey M. Trent at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancer and nutrition-norfolk.

Subjects of this study consisted of 333 women (aged 45-75 years) drawn from a large United Kingdom prospective study of diet and cancer, the European Prospective Investigation of Cancer and Nutrition-Norfolk study. Using newly developed gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry methods incorporating triply (13)C-labeled standards, seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in 114 spot urines and 97 available serum samples from women who later developed breast cancer. Results were compared with those from 219 urines and 187 serum samples from healthy controls matched by age and date of recruitment. Dietary levels were low, but even so, mean serum levels of phytoestrogens were up to 600 times greater than postmenopausal estradiol levels. Phytoestrogen concentrations in spot urine (adjusted for urinary creatinine) correlated strongly with that in serum, with Pearson correlation coefficients > 0.8. There were significant relationships (P < 0.02) between both urinary and serum concentrations of isoflavones across increasing tertiles of dietary intakes. Urinary enterodiol and enterolactone and serum enterolactone were significantly correlated with dietary fiber intake (r = 0.13-0.29). Exposure to all isoflavones was associated with increased breast cancer risk, significantly so for equol and daidzein. For a doubling of levels, odds ratios increased by 20-45% [log(2) odds ratio = 1.34 (1.06-1.70; P = 0.013) for urine equol, 1.46 (1.05-2.02; P = 0.024) for serum equol, and 1.22 (1.01-1.48; P = 0.044) for serum daidzein]. These estimates of risk are similar to those established for estrogens and androgens in postmenopausal breast cancer but need confirmation in larger studies.     

Phytoestrogen and cancer prevention

Phytoestrogens are defined to be plant chemicals that modify estrogenic effects in the body by binding to the estrogen receptors in mammals. Isoflavones, coumestane, lignan, and prenylflavones are examples of these, with isoflavones from soy foods and lignans from rye being a major dietary contribution. Mechanisms of cancer prevention by these phytoestrogens are reviewed, and human epidemiological studies, especially for breast and prostate cancers, are summarized and the results discussed.     

Dietary intake of isoflavones and coumestrol and the risk of prostate cancer in the Prostate,Lung, Colorectal and Ovarian Cancer Screening Trial

Experimental studies have revealed that phytoestrogens may modulate the risk of certain sites of cancer due to their structural similarity to 17β‐estradiol. The present study investigates whether intake of these compounds may influence prostate cancer risk in human populations. During a median follow up of 11.5 years, 2,598 cases of prostate cancer (including 287 advanced cases) have been identified among 27,004 men in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Dietary intake of phytoestrogens (excluding lignans) was assessed with a food frequency questionnaire. Cox proportional hazards regression analysis was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for dietary isoflavones and coumestrol in relation to prostate cancer risk. After adjustment for confounders, an increased risk of advanced prostate cancer [HR (95% CI) for quintile (Q) 5 vs. Q1] was found for the dietary intake of total isoflavones [1.91 (1.25–2.92)], genistein [1.51 (1.02–2.22), daidzein [1.80 (1.18–2.75) and glycitein [1.67 (1.15–2.43)] (p‐trend for all associations ≤0.05). For example, HR (95% CI) for comparing the Q2, Q3, Q4 and Q5 with Q1 of daidzein intake was 1.45 (0.93–2.25), 1.65 (1.07–2.54), 1.73 (1.13–2.66) and 1.80 (1.18–2.75), respectively (p‐trend: 0.013). No statistically significant associations were observed between the intake of total isoflavones and individual phytoestrogens and non‐advanced and total prostate cancer after adjustment for confounders. This study revealed that dietary intake of isoflavones was associated with an elevated risk of advanced prostate cancer.     

Alcohol and Breast Cancer Mortality in a Cohort Study

Available epidemiological evidence indicates that alcohol intake is associated with a higher risk of developing breast cancer. Plausible biological pathways include its effect on levels of estrogens, cell membrane integrity and cell-to-cell communication, inhibition of DNA repair, and congener effect. The present study evaluated the impact of alcohol on mortality from breast cancer, an area with relatively few studies in the literature. The subjects were participants in a Canadian prospective cohort study, the National Breast Screening Study (NBSS). Women were enrolled in the cohort from 1980 to 1985 to evaluate the efficacy of mammographic screening. Information on usual diet and alcohol intake at enrolment and other epidemiological variables was collected by means of a mailed, self-administered questionnaire. Mortality from breast cancer during follow- up to 31 December, 1993 was ascertained by record linkage to the Canadian Mortality Data Base maintained by Statistics Canada. During the follow-up period of 1980–1993 (average 10.3 years), 223 deaths from breast cancer were identified for this analysis. The hazard ratios for the risk of death from breast cancer increased with intakes of total alcohol of 10–20g/day (1.039, 1.009–1.071) and >20g/day (1.063, 1.029–1.098). This increase was contributed largely by the intake of wine, a 15% increase in risk at intakes higher than 10g/day of alcohol from wine. Alcohol from spirits was associated with a small decrease in risk of death (hazard ratio at 10g/day, 0.945, 0.915–0.976). The effect of alcohol from beer was not significant in the two categories studied. Although our results were statistically significant, the magnitude of the change in risk was small.     

Phytoestrogen consumption and endometrial cancer risk: a population-based case–control study in New Jersey

Phytoestrogens have been shown to exert anti-estrogenic and estrogenic effects in some tissues, including the breast. However, only a few studies have evaluated their role in endometrial cancer risk. We evaluated this association in a population-based case–control study in New Jersey. A total of 424 cases and 398 controls completed an interview, including a food frequency questionnaire with supplemental questions for phytoestrogen foods. Risk estimates were derived using an unconditional logistic regression, adjusting for major risk factors for endometrial cancer. There was some suggestion of a decreased risk with quercetin intake (OR: 0.65; 95% CI: 0.41–1.01 for the highest compared to the lowest quartile; p for trend: 0.02). We found a limited evidence of an association with any of the lignans evaluated, total lignans, coumestrol, individual isoflavones, total isoflavones, or total phytoestrogens. However, there was some suggestion of an inverse association with total isoflavone intake limited to lean women (BMI <25; OR for the highest tertile: 0.50; 95% CI: 0.25–0.98) and those with a waist-to-hip ratio ≤0.85 (OR: 0.59; 95% CI: 0.33–1.05). There was no evidence of effect modification by HRT use. This study suggests a reduction in endometrial cancer risk with quercetin intake and with isoflavone intake in lean women.     

The Association between Dairy Intake and Breast Cancer in Western and Asian Populations: A Systematic Review and Meta-Analysis

Purpose

To date, studies investigating the association between dairy consumption and breast cancer in women have produced conflicting results. As diet is an important, modifiable factor affecting cancer development, the aim of this study was to examine the association between dairy consumption and breast cancer risk.

Methods

PubMed, Embase, and Cochrane Library databases were searched with a priority for prospective cohort studies. Case-control studies were also considered in case of the absence of a cohort study.

Results

We analyzed 22 prospective cohort studies (1,566,940 participants) and five case-control studies (33,372 participants). High and modest dairy consumption (>600 and 400-600 g/day, respectively) significantly reduced the risk of breast cancer compared with low dairy consumption (<400 g/day; risk ratio [RR], 0.90, 95% confidence interval [CI], 0.83-0.98, and RR, 0.94, 95% CI, 0.91-0.98, respectively). A significant linear relationship between dairy consumption and breast cancer risk was found on dose-response analysis. Subgroup analysis found that yogurt (RR, 0.91; 95% CI, 0.83-0.99) and low-fat dairy (RR, 0.85; 95% CI, 0.75-0.96) reduced the risk of breast cancer, while other dairy product types did not. A reduced risk was observed for people in the United States (RR, 0.91; 95% CI, 0.83-0.99) and in those followed for ≥10 years (RR, 0.90; 95% CI, 0.81-0.99). Additionally, the highest level of dairy consumption among Asians was associated with a reduced risk of breast cancer (odds ratio, 0.74; 95% CI, 0.62-0.88).

Conclusion

Dairy consumption was inversely associated with the risk of developing breast cancer and this effect was dependent on the dose, dairy-type, and time.     

Physical activity and breast cancer risk: the Women's Health Study (United States)

Objective: It is biologically plausible for physical activity to decrease breast cancer risk; however, epidemiologic studies have yielded inconsistent findings. We therefore examined physical activity and breast cancer risk in the Women's Health Study. Methods: We assessed physical activity among 39,322 apparently healthy women, aged 45 years, and prospectively followed them for an average of 48 months. Four hundred eleven women developed breast cancer, with 222 positive for both estrogen and progesterone receptors. Results: Among all women the multivariate relative risks of all breast cancer associated with <840, 840–2519, 2520–6299, and 6300 kJ/week expended on recreational activities and stair climbing were 1.00 (referent), 1.04 (95% confidence interval, 0.77–1.40), 0.86 (0.64–1.17), and 0.80 (0.58–1.12), respectively; p-trend = 0.11. However, among postmenopausal women there was a significant inverse trend for all breast cancer; the corresponding relative risks were 1.0 (referent), 0.97 (0.68–1.4), 0.78 (0.54–1.1), and 0.67 (0.44–1.0), respectively; p-trend = 0.03. Physical activity was unrelated to breast cancers positive for both estrogen and progesterone receptors either among all or postmenopausal women (p-trend = 0.50 and 0.26, respectively). When we assessed only vigorous recreational activity, requiring 6 METs or multiples of resting metabolic rate, we observed no significant associations with all or steroid hormone receptor positive breast cancer, either among all or postmenospausal women. Conclusions: These data suggest that physical activity during middle age and older is not uniformly associated with decreased breast cancer risk. Among postmenopausal women only, higher levels of physical activity may decrease the risk of breast cancer. This study, however, had limited statistical power to detect small effects.