The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol ...(HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95 % CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0·97 (95 % CI 0·94, 1·00; dose–response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0·86 (95 % CI 0·69, 1·09; dose–response per 1 mmol/l increment, six studies), with high heterogeneity (I
2= 67 and 47 %, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose–response HR 0·94 (95 % CI 0·89, 0·99), seven studies, I
2= 78 %; highest v. lowest HR 0·82 (95 % CI 0·66, 1·02), nine studies, I
2= 81 %) and HDL-C (dose–response HR 0·81 (95 % CI 0·65, 1·02), five studies, I
2= 30 %; highest v. lowest HR 0·82 (95 % CI 0·69, 0·98), five studies, I
2= 0 %). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.
In addition to tumor characteristics and lifestyle factors, cancer relapses are often related to the risk of death but have not been jointly studied. We investigate the prognostic factors of ...recurrent events and death after a diagnosis of breast cancer and predict individual deaths including a history of recurrences.
The E3N (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale) study is a prospective cohort study that was initiated in 1990 to investigate factors associated with the most common types of cancer. Overall survival and three types of recurrent events were considered: locoregional recurrence, metastasis, and second primary breast cancer. Recurrent events and death were analyzed using a joint frailty model.
The analysis included 4926 women from the E3N cohort diagnosed with a first primary invasive breast cancer between June 1990 and June 2008; during the follow-up, 1334 cases had a recurrence (median time of follow-up is 7.2 years) and 469 women died. Cases with high grade, large tumor size, axillary nodal involvement, and negative estrogen and progesterone receptors had a higher risk of recurrence or death. Furthermore, smoking increased the risk of relapse. For cases with a medium risk profile in terms of tumor characteristics and lifestyle factors, the probability of dying between 5 and 10 years after diagnosis was 6, 20 and 36% for 0, 1 or 2 recurrences within the first 5 years after diagnosis, respectively.
Our study showed the importance of considering baseline lifestyle characteristics and history of relapses to dynamically predict the risk of death in breast cancer cases. Medical experience coupled with an estimate of a patient's survival probability that considers all available information for this patient would enable physicians to make better informed decisions regarding their actions and thus improve clinical output.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mechanistic hypotheses suggest a potential effect of dietary fiber on breast carcinogenesis through the modulation of insulin-like growth factor bioactivity, estrogen metabolism and inflammation. An ...association between dietary fiber intake and breast cancer risk has been suggested in epidemiological studies but remains inconclusive. In particular, data is lacking regarding the different types of dietary fibers.
The objective was to investigate the prospective relationship between dietary fiber intake and breast cancer risk, taking into account different types of dietary fiber (overall, insoluble, soluble and from different food sources: cereals, vegetables, fruits and legumes).
4684 women from the SU.VI.MAX cohort were included in this analysis as they completed at least three 24h-dietary records within the first two years of follow-up. Among them, 167 incident invasive breast cancers were diagnosed during a median follow-up of 12.6 years (between 1994 and 2007). The associations between quartiles of dietary fiber intake and breast cancer risk were characterized using multivariate Cox proportional hazards models.
Total fiber intake was not associated with breast cancer risk (HR(Quartile4vs.Quartile1) = 1.29 (95%CI 0.66-2.50), P-trend = 0.5), nor was fiber intake from cereals (P-trend = 0.1), fruits (P-trend = 0.9) and legumes (P-trend = 0.3). In contrast, vegetable fiber intake was related to a decreased risk of breast cancer (HR(Q4vs.Q1) = 0.50 (0.29-0.88), P-trend = 0.03). Overall vegetable intake (in g/day) was not associated with breast cancer risk (P-trend = 0.2).
This prospective study suggests that vegetable fiber intake may contribute to reduce breast cancer risk, in line with experimental mechanistic data.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify ...circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density.
A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers' Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors.
Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components.
We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.
Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study ...investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association.
Many studies have demonstrated that lifestyle factors, including diet, may influence cancer survival. The number of cancer survivors is increasing worldwide and little is known about long‐term diet ...changes in people who had cancer. We studied 53,981 women from the prospective E3N‐EPIC cohort study with available dietary data in 1993 and 2005, among whom 4,619 had a cancer diagnosis inbetween (including n = 2,699 breast cancers). We evaluated the potential impact of a cancer diagnosis (comparing women with cancer to women with no cancer) on changes in FV consumption using multivariable linear regression models considering cancer site, stage at diagnosis and socioeconomic factors. Compared to women with no cancer, a statistically significant increase in FV consumption (β=+2.65%, 1.22–4.09) was observed in women who had cancer, and this association appeared to be driven by breast cancer exclusively. The increase in FV consumption was larger in women who had an advanced stage of breast cancer (stages II–IV) (β=+7.23%, 3.92–10.5) than in women with stages 0–I (β=+2.03%, −0.20 to 4.26). Women with no partner and no children were those having the highest increase in FV consumption (β=+18.71%, 6.51–30.91). These changes were only observed in specific SE groups. When considering adherence to guidelines, the proportion of women who consumed less than 7.5 portions a day in 1993 and more in 2005 was greater in women with advanced breast cancer. More research is now needed to understand how the inequities we observed impact the long‐term health after cancer.
What's new?
Eat a diet rich in fruits and vegetables, doctors say, to prevent cancer. But will eating more fruits and vegetables after diagnosis improve the chances of survival? Here, the authors looked at dietary data from women in the EPIC cohort study, over a 12‐year period, to see whether a cancer diagnosis would spur women to change their diet. Women diagnosed with advanced breast cancer, they found, significantly increased their fruit and vegetable consumption, compared with women who were not diagnosed. The improvements in diet, however, were seen only in women in certain socioeconomic groups.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer ...development, but data is limited in premenopausal women, especially in Latin America.
We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors.
IL-6 (OR
= 1.33 (1.11-1.60)) and TNF-α (OR
= 1.32 (1.11-1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only.
The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.
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Cumulating evidence in Caucasian women suggests a positive association between height and premenopausal breast cancer risk and a negative association with overall adiposity; however data from Latin ...America are scarce. We investigated the associations between excess adiposity, body shape evolution across life, and risk of premenopausal breast cancer among 406 cases (women aged 20-45) and 406 matched population-based controls from Chile, Colombia, Costa Rica, and Mexico. Negative associations between adult adiposity and breast cancer risk were observed in adjusted models (body mass index (BMI): Odds ratio (OR) per 1 kg/m
= 0.93; 95% confidence interval = 0.89-0.96; waist circumference (WC): OR per 10 cm = 0.81 (0.69-0.96); hip circumference (HC): OR per 10 cm = 0.80 (0.67-0.95)). Height and leg length were not associated with risk. In normal weight women (18.5 ≤ BMI < 25), women with central obesity (WC > 88 cm) had an increased risk compared to women with normal WC (OR = 3.60(1.47-8.79)). Residuals of WC over BMI showed positive associations when adjusted for BMI (OR per 10 cm = 1.38 (0.98-1.94)). Body shape at younger ages and body shape evolution were not associated with risk. No heterogeneity was observed by receptor status. In this population of Latin American premenopausal women, different fat distributions in adulthood were differentially associated with risk of breast cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
There is convincing evidence demonstrating that body size characteristics such as adiposity and height are associated with breast cancer in westernized countries. However, little is known ...about this relationship in North African countries currently undergoing nutritional transition and industrialization. The aim of this study was to explore associations between various body size characteristics, silhouette trajectories and the risk of breast cancer among Moroccan women.
Methods
In this case–control study conducted in the Fez region (2016–2017), detailed measures of body size were collected for 300 cases of breast cancer and 300 matched controls. Unconditional logistic regression was used to assess the association between body size and breast cancer risk adjusting for confounding factors.
Results
Higher waist circumference and hip circumference were positively associated with breast cancer risk in pre- (highest T3 vs. lowest tertile T1: OR = 2.92, 95% confidence intervals CI: 1.33–6.42; OR = 3.00, 95% CI: 1.42–6.33, respectively) and post-menopausal women (T3 vs. T1: OR = 4.46, 95% CI: 1.86–10.66; OR = 4.08, 95% CI: 1.76–9.42, respectively). Body shape at younger ages (6–11 years) was inversely associated with the risk of breast cancer in premenopausal women (large vs. lean silhouette: OR = 0.31, 95% CI: 0.12–0.80). Women with the greatest increase in body shape trajectory had higher risk for both pre- and post-menopausal breast cancer (T3 vs. T1: OR = 2.74, 95% CI: 1.03–7.26; OR = 3.56, 95% CI: 1.34–9.44, respectively).
Conclusion
Our findings suggest that adiposity, body shape at younger ages, and silhouette trajectory may play a role in the development of pre- and post-menopausal breast cancer among Moroccan women. Larger-scale prospective studies are needed to confirm our findings and to explore these associations with breast cancer subtypes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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