Smoking at time of diagnosis and breast cancer-specific survival: new findings and systematic review with meta-analysis.

INTRODUCTION: In women with breast cancer who smoke, it is unclear whether smoking could impair their survival from the disease. METHODS: We examined the relation of smoking at diagnosis to breast cancer-specific and overall survival among 5,892 women with invasive breast cancer treated in one Canadian center (1987 to 2008). Women were classified as never, former or current smokers. Current smokers were further classified according to total, intensity and duration of smoking. Deaths were identified through linkage to population mortality data. Cox proportional-hazards multivariate models were used. A systematic review with meta-analysis combines new findings with published results. RESULTS: Compared with never smokers, current smokers at diagnosis had a slightly, but not statistically significant, higher breast cancer-specific mortality (hazard ratio = 1.15, 95% confidence interval (CI): 0.97 to 1.37). Among current smokers, breast cancer-specific mortality increased with total exposure to, intensity and duration of smoking (all Ptrend <0.05). Compared to never smokers, breast cancer-specific mortality was 32 to 56% higher among heavy smokers (more than 30 pack years of smoking, more than 20 cigarettes per day or more than 30 years of smoking). Smoking at diagnosis was associated with an increased all-cause mortality rate. A meta-analysis of all studies showed a statistically significant, 33% increased mortality from breast cancer in women with breast cancer who are smokers at diagnosis compared to never smokers (hazard ratio = 1.33, 95% CI: 1.12 to 1.58). CONCLUSIONS: Available evidence to date indicates that smoking at diagnosis is associated with a reduction of both overall and breast cancer-specific survival. Studies of the effect of smoking cessation after diagnosis on breast cancer-specific outcomes are needed.

Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population.

Vitamin D has been associated with reduced breast cancer risk. We studied the association of two vitamin D receptor (VDR) gene single nucleotide polymorphisms restriction enzyme detecting SNP of VDR (FokI and BsmI) with breast cancer risk in two independent case-control studies carried out in the same population. The modifying effect of family history of breast cancer on this relationship was also evaluated. The first and second studies included respectively 718 (255 cases/463 controls) and 1596 (622 cases/974 controls) women recruited in Quebec City, Canada. FokI and BsmI genotypes were assessed. Relative risks of breast cancer were estimated by multivariate logistic regression. Compared with homozygotes for the common F allele (FF genotype), FokI ff homozygotes had a higher breast cancer risk (study 1: odds ratio (OR)=1.22, 95% confidence interval (CI)=0.76-1.95; study 2: OR=1.44, 95% CI=1.05-1.99; and combined studies: OR=1.33, 95% CI=1.03-1.73). Significant interactions were observed between FokI and family history of breast cancer in the two studies as well as in the combined analysis (P interaction=0.031, 0.050 and 0.0059 respectively). Among women without family history, odds ratios were 1.00, 1.27 (95% CI=1.02-1.58) and 1.57 (95% CI=1.18-2.10) respectively for FF, Ff and ff carriers (P(trend)=0.0013). BsmI Bb+bb genotypes were associated with a weak non-significant increased risk in the two studies (combined OR=1.22, 95% CI=0.95-1.57) without interaction with family history. Results support the idea that vitamin D, through its signalling pathway, can affect breast cancer risk. They also suggest that variability in observed associations between VDR FokI and breast cancer from different studies may partly be explained by the proportion of study subjects with a family history of breast cancer.

Intact and total insulin-like growth factor-binding protein-3 (IGFBP-3) levels in relation to breast cancer risk factors: a cross-sectional study.

INTRODUCTION: Levels of insulin-like growth factor (IGF)-I and its main binding protein (IGFBP-3) have been associated with breast cancer risk among premenopausal women. However, associations of IGFBP-3 levels with breast cancer risk have been inconsistent, possibly due to the different predominant forms of circulating IGFBP-3 (intact versus fragmented) that were measured in these studies. Here, we examine the association of breast cancer risk factors with intact and total IGFBP-3 levels. METHODS: This cross-sectional study includes 737 premenopausal women recruited at screening mammography. Plasma intact and total IGFBP-3 and IGF-I levels were measured by enzyme-linked immunosorbent assay methods. Percent and absolute breast density were estimated using a computer-assisted method. The associations were evaluated using generalized linear models and Pearson (r) or Spearman (rs) partial correlation coefficients. RESULTS: Means +/- standard deviations of intact and total IGFBP-3 levels (ng/mL) were 1,044 +/- 234 and 4,806 +/- 910, respectively. Intact and total IGFBP-3 levels were correlated with age and smoking. Levels of intact IGFBP-3 were negatively correlated with waist-to-hip ratio (WHR) (r = -0.128; P = 0.0005), parity (rs = -0.078; P = 0.04), and alcohol intake (r = -0.137; P = 0.0002) and positively correlated with energy intake (r = 0.075; P = 0.04). In contrast, total IGFBP-3 levels were positively correlated with WHR (r = 0.115; P = 0.002), parity (rs = 0.089; P = 0.02), body mass index (BMI) (r = 0.115; P = 0.002), physical activity (r = 0.118; P = 0.002), and IGF-I levels (r = 0.588; P < 0.0001) and negatively correlated with percent or absolute breast density (r = -0.095; P = 0.01 and r = -0.075; P = 0.04, respectively). CONCLUSION: Our data show that associations of some breast cancer risk factors with intact levels of IGFBP-3 are different from those with total (intact and fragmented) IGFBP-3 levels. These findings suggest that different molecular forms of IGFBP-3 may bear different relations to premenopausal breast cancer risk.

Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels.

The insulin-like growth factor (IGF) pathway is believed to play a role in carcinogenesis of the mammary gland. Single nucleotide polymorphisms (SNPs) of IGF-I, IGF-binding protein-3 (IGFBP-3), IGF receptor 1, insulin receptor substrate 1, and phosphoinositide-3-kinase, catalytic, beta polypeptide genes, which are members of the IGF pathway, have been associated with risk of common cancers, breast density, and/or IGF levels but results remain inconclusive. Thus, we evaluated the association of 11 targeted IGF pathway SNPs with circulating IGF levels and mammographic breast density. Among 741 white premenopausal women, blood samples were collected at time of screening mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Percent and absolute breast density were estimated using a computer-assisted method. Multivariate linear models were used to examine the associations. Women carrying increasing number of copies of the rare allele of IGF-I rs1520220 and rs6220 SNPs had increased percent breast density (P(trend) = 0.04 and 0.06, respectively). Carriers of increasing number of copies of the rare allele of phosphoinositide-3-kinase, catalytic, beta polypeptide rs361072 SNP had decreased percent (P(trend) = 0.04) and absolute (P(trend) = 0.02) breast density. An association of insulin receptor substrate 1 rs1801278 SNP with absolute density (P(trend) = 0.03) was also observed. All four IGFBP-3 SNPs (including rs2854744) were associated with IGF-I and IGFBP-3 levels. This study shows that several components of the IGF pathway are associated with breast density or IGF levels. Our findings provide additional support for the idea that several components of the IGF pathway may affect breast cancer risk and that this effect on breast cancer development may be mediated, at least in part, through its influence on the morphogenesis of breast tissue.

Influence of insulin-like growth factors on the strength of the relation of vitamin D and calcium intakes to mammographic breast density.

Diets with higher vitamin D and calcium contents were found associated with lower mammographic breast density and breast cancer risk in premenopausal women. Because laboratory studies suggest that the actions of vitamin D, calcium, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 (IGFBP-3) on human breast cancer cells are interrelated, we examined whether IGF-I and IGFBP-3 levels could affect the strength of the association of vitamin D and calcium intakes with breast density. Among 771 premenopausal women, breast density was measured by a computer-assisted method, vitamin D and calcium intakes by a food frequency questionnaire, and levels of plasma IGF-I and IGFBP-3 by ELISA methods. Multivariate linear regression models were used to examine the associations and the interactions. The negative associations of vitamin D or calcium intakes with breast density were stronger among women with IGF-I levels above the median (beta = -2.8, P = 0.002 and beta = -2.5, P = 0.002, respectively) compared with those with IGF-I levels below or equal to the median (beta = -0.8, P = 0.38 and beta = -1.1, P = 0.21; P(interaction) = 0.09 and 0.16, respectively). Similar results were observed within levels of IGFBP-3 (P(interaction) = 0.06 and 0.03, respectively). This is the first study to report that the negative relation of vitamin D and calcium intakes with breast density may be seen primarily among women with high IGF-I or high IGFBP-3 levels. Our findings suggest that the IGF axis should be taken into account when the effects of vitamin D and calcium on breast density (and perhaps breast cancer risk) are examined at least among premenopausal women.

Synchronized seasonal variations of mammographic breast density and plasma 25-hydroxyvitamin d.

BACKGROUND: Dietary vitamin D has been associated with lower mammographic breast density, a strong biomarker for breast cancer risk. Blood 25-hydroxyvitamin D [25(OH)D] is an integrated measure of vitamin D status (from food, supplements, and sun exposure) and varies with season. Our objective was to assess seasonal variations of breast density and compare such variations, if any, with that of 25(OH)D. METHODS: This cross-sectional study includes 741 premenopausal women recruited at screening mammography. Plasma 25(OH)D at recruitment was measured by RIA. Breast density was evaluated using a computer-assisted method. Seasonal variations were modeled using multivariate linear regression and semi-parametric cubic smoothing splines. RESULTS: Season was strongly associated with 25(OH)D (P < 0.0001). The highest smoothed mean 25(OH)D levels were seen at the end of July (81.5 nmol/L) and the lowest in mid-April (52.4 nmol/L). Breast density showed modest seasonal variations (P = 0.028). The lowest smoothed mean breast density was observed in early December (38.5%) and the highest at the beginning of April (44.3%). When a 4-month lag time was presumed, seasonal variations of breast density appeared to be a mirror image of those of 25(OH)D, and the correlation of daily smoothed estimates of mean breast density and 25(OH)D was negative and strong (r = -0.90). CONCLUSION: In premenopausal women, changes in blood vitamin D seem to be inversely related to changes in breast density with a lag time of about 4 months. This finding encourages further investigation of the possibility that vitamin D could reduce breast density and breast cancer risk.

Plasma concentrations of selected organobromine compounds and polychlorinated biphenyls in postmenopausal women of Québec, Canada.

BACKGROUND: Brominated flame retardants, especially polybrominated diphenyl ethers (PBDEs), have been widely used in North America, but little is known about the level of exposure of human populations to these compounds. OBJECTIVES: We set out to assess the internal exposure of postmenopausal Canadian women to selected organobromine compounds and to investigate factors associated with this exposure. METHODS: We measured concentrations of four PBDEs, one polybrominated biphenyl, and for comparative purposes, 41 polychlorinated biphenyl (PCB) congeners in plasma samples from 110 healthy postmenopausal women who were recruited at a mammography clinic in 2003-2004. RESULTS: PBDE-47 was the major PBDE congener, with a mean (geometric) concentration of 8.1 ng/g lipids and extreme values reaching 1,780 ng/g. By comparison, the mean concentration of the major PCB congener (PCB-153) was 41.7 ng/g and the highest value was 177 ng/g. PBDEs 47, 99, and 100 were strongly intercorrelated, but weaker correlations were noted with PBDE-153. As the sum of PBDEs (summation operatorPBDEs) increased, the relative contribution of PBDE-47 to the summation operatorPBDEs increased, whereas that of PBDE-153 decreased. PBDE-153 was the only brominated compound correlated to PCB-153. PBDE levels were not linked to any sociodemographic, anthropometric, reproductive, or lifestyle variables documented in the present study. Age and body mass index gain since the age of 18 years were significant predictors of PCB-153 plasma levels. CONCLUSION: Our results suggest that exposure to PBDE-47 likely occurs through direct contact with the penta-PBDE formulation, whereas exposure to PBDE-153 may originate in part from the food chain.

A Randomized Double-Blind Placebo-Controlled Trial of the Effect of Vitamin D3 Supplementation on Breast Density in Premenopausal Women.

Background: This double-blind, placebo-controlled parallel group trial assessed whether oral supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 over one year reduces percent mammographic breast density in premenopausal women.Methods: The trial was conducted between October 2012 and June 2015, among premenopausal female volunteers from Quebec City (Quebec, Canada). Women were randomized with ratio 1:1:1:1 to one of four study arms (1,000, 2,000, or 3,000 IU/day vitamin D3 or placebo). The primary outcome was mean change in percent mammographic breast density. Participants and research team were blinded to study arm assignment.Results: Participants (n = 405) were randomized to receive 1,000 (n = 101), 2,000 (n = 104), or 3,000 IU/day (n = 101) vitamin D3, or a placebo (n = 99). The primary analysis included 391 participants (96, 99, 100, and 96, respectively). After the one-year intervention, mean ± SE change in percent breast density in the arms 1,000 IU/day (-5.5% ± 0.5%) and 2,000 IU/day (-5.9% ± 0.5%) vitamin D3 was similar to that in the placebo arm (-5.7% ± 0.5%) (P values = 1.0). In the 3,000 IU/day vitamin D3 arm, percent breast density also declined but slightly less (-3.8% ± 0.5%) compared with placebo arm (P = 0.03). Adherence to intervention was excellent (92.8%), and reporting of health problems was comparable among study arms (P ≥ 0.95). All participants had normal serum calcium.Conclusions: In premenopausal women, one-year supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 resulted in a reduction of percent breast density no greater than that seen with the placebo.Impact: At doses of 1,000-3,000 IU/day, vitamin D supplementation will not reduce breast cancer risk through changes in breast density. Cancer Epidemiol Biomarkers Prev; 26(8); 1233-41. ©2017 AACR.

Relation of insulin-like growth factor (IGF) I and IGF-binding protein 3 concentrations with intakes of fruit, vegetables, and antioxidants.

BACKGROUND: Fruit, vegetable, and antioxidant intakes may reduce the risk of several insulin-like growth factor (IGF)-related chronic diseases, such as certain types of cancers and cardiovascular diseases. OBJECTIVE: This study investigated whether intakes of fruit, vegetables, and antioxidants (beta-carotene, lycopene, and vitamin C) are associated with plasma IGF-I and IGF-binding protein 3 (IGFBP-3) concentrations. DESIGN: Plasma IGF-I and IGFBP-3 concentrations were measured in 1542 healthy women by enzyme-linked immunosorbent assay. A self-administered semiquantitative food-frequency questionnaire was used to estimate mean daily dietary intakes of fruit, vegetables, and antioxidants over the year preceding blood sampling. Multivariate analyses were performed by using generalized linear models to evaluate the association of quintiles of daily intakes with concentrations of growth factors. RESULTS: A higher intake of citrus fruit was associated with higher concentrations of IGF-I (215 ng/mL for quintile 5 compared with 205 ng/mL for quintile 1; P for trend = 0.04) and with lower concentrations of IGFBP-3 (4803 ng/mL for quintile 5 compared with 4960 ng/mL for quintile 1; P for trend = 0.04). Higher dietary vitamin C intake was associated with higher concentrations of IGF-I (214 ng/mL for quintile 5 compared with 204 ng/mL for quintile 1; P for trend = 0.02) and lower concentrations of IGFBP-3 (4813 ng/mL for quintile 5 compared with 4953 ng/mL for quintile 1; P for trend = 0.03). Total intake of fruit and vegetables and intakes of other botanical fruit and vegetable subgroups, beta-carotene, and lycopene were not related to either IGF-I or IGFBP-3 concentrations. CONCLUSION: Women with higher intakes of citrus fruit or dietary vitamin C tend to have higher plasma concentrations of IGF-I and lower plasma concentrations of IGFBP-3.

Insulin-like growth factor-I, IGF-binding protein-3, and mammographic breast density.

Some studies have suggested that insulin-like growth factor (IGF) pathway is related to premenopausal breast density, one of the strongest known breast cancer risk factors. This study was designed specifically to test the hypothesis that higher levels of IGF-I and lower levels of IGF-binding protein (IGFBP)-3 are associated with high mammographic breast density among premenopausal but not among postmenopausal women. A total of 783 premenopausal and 791 postmenopausal healthy women were recruited during screening mammography examinations. Blood samples were collected at the time of mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Mammographic breast density was estimated using a computer-assisted method. Spearman's partial correlation coefficients (r(s)) were used to evaluate the associations. Adjusted mean breast density was assessed by joint levels of IGF-I and IGFBP-3 using generalized linear models. Among premenopausal women, high levels of IGF-I and low levels of IGFBP-3 were independently correlated with high breast density (r(s) = 0.083; P = 0.021 and r(s) = -0.124; P = 0.0005, respectively). Correlation of IGF-I with breast density was stronger among women in the lowest tertile of IGFBP-3 than among those in the highest tertile of IGFBP-3 (r(s) = 0.138; P = 0.027 and r(s) = -0.039; P = 0.530, respectively). In contrast, the correlation of IGFBP-3 with breast density was stronger among women in the highest tertile of IGF-I than among those in the lowest tertile of IGF-I (r(s) = -0.150; P = 0.016 and r(s) = -0.008; P = 0.904, respectively). Women in the combined top tertile of IGF-I and bottom tertile of IGFBP-3 had higher mean breast density than those in the combined bottom tertile of IGF-I and top tertile of IGFBP-3 (53.8% versus 40.9%; P = 0.014). No significant association was observed among postmenopausal women. Our findings confirm that IGF-I and IGFBP-3 are associated with breast density among premenopausal women. They provide additional support for the idea that, among premenopausal women, these growth factors may affect breast cancer risk, at least in part, through their influence on breast tissue morphology as reflected on mammogram.

Vitamin D and calcium intakes from food or supplements and mammographic breast density.

BACKGROUND: A better understanding of factors that affect breast density, one of the strongest breast cancer risk indicators, may provide important clues about breast cancer etiology and prevention. This study evaluates the association of vitamin D and calcium, from food and/or supplements, to breast density in premenopausal and postmenopausal women separately. METHODS: A total of 777 premenopausal and 783 post-menopausal women recruited at two radiology clinics in Quebec City, Canada, in 2001 to 2002, completed a food frequency questionnaire to assess vitamin D and calcium. Breast density from screening mammograms was assessed using a computer-assisted method. Associations between vitamin D or calcium and breast density were evaluated using linear regression models. Adjusted means in breast density were assessed according to the combined daily intakes of the two nutrients using generalized linear models. RESULTS: In premenopausal women, total intakes of vitamin D and calcium were inversely related to breast density (beta = -1.4; P = 0.004 for vitamin D; beta = -0.8; P = 0.0004 for calcium). In multivariate linear regression, simultaneous increments in daily total intakes of 400 IU vitamin D and 1,000 mg calcium were associated with an 8.5% (95% confidence interval, 1.8-15.1) lower mean breast density. The negative association between dietary vitamin D intake and breast density tended to be stronger at higher levels of calcium intake and vice versa. Among postmenopausal women, intakes of vitamin D and calcium were not associated with breast density. CONCLUSION: These findings show that higher intakes of vitamin D and calcium from food and supplements are related to lower levels of breast density among premenopausal women. They suggest that increasing intakes of vitamin D and calcium may represent a safe and inexpensive strategy for breast cancer prevention.

Levels of C-peptide and mammographic breast density.

Members of the insulin-like growth factor family have been associated with breast cancer risk and mammographic breast density, one of the strongest known breast cancer risk indicators. The aim of this cross-sectional study was to examine the association of levels of C-peptide (a marker of insulin secretion) with mammographic breast density among 1,499 healthy women recruited during screening mammography examinations. At time of mammography, blood samples and time since last meal were collected. Plasma C-peptide levels were measured by ELISA method, and mammographic breast density by a computer-assisted method. Spearman's partial correlation coefficients, adjusting for age and time since last meal (when necessary), were used to evaluate the associations. High body mass index and waist-to-hip ratio measurements were independently correlated with high levels of C-peptide (r(s) = 0.173 and r(s) = 0.252, respectively; P < 0.0001) or low breast density (r(s) = -0.389 and r(s) = -0.142, respectively; P < 0.0001). High levels of C-peptide were correlated with low breast density (r(s) = -0.210, P < 0.0001). However, the strength of the negative correlation was substantially reduced and was no longer significant after further adjustment for body mass index and waist-to-hip ratio (r(s) = -0.022, P = 0.41). These results suggest that C-peptide levels are not associated with breast density after complete adjustment for adiposity. Thus, the insulin/C-peptide-breast density relation does not seem to mirror the insulin/C-peptide-breast cancer association.

Vitamin D, calcium, and mammographic breast densities.

Vitamin D and calcium are being evaluated as potential breast cancer prevention agents. This study reports on the relation of dietary vitamin D and calcium to mammographic breast densities, one of the strongest breast cancer risk factors. Participants were women ages 40 to 60 years who had had a screening mammogram in Rhode Island and eastern Massachusetts (1989-1990). Diet was assessed by semiquantitative food frequency questionnaire, and the percentage of the breast showing densities was estimated visually by a single observer without information on subjects. Multivariate logistic regression was used to compare dietary intakes of vitamin D and calcium between women classified as having few densities (< or =30% of the breast with density, n = 287) and extensive densities (> or =70% of the breast with density, n = 256). For categories of increasing vitamin D intake (<50, 50-99, 100-199, and > or =200 IU/d), adjusted odds ratios (OR) for extensive densities were 1.00 (reference), 0.51, 0.37, and 0.24, respectively (P for trend = 0.0005). For increasing calcium intake (<500, 500-749, 750-999, and > or =1,000 mg/d), adjusted ORs were 1.00 (reference), 0.63, 0.25, and 0.24, respectively (P for trend = 0.0006). Combination of higher intakes of vitamin D and calcium (> or =100 IU/d and > or =750 mg/d, respectively) were associated with a reduction of breast densities (OR, 0.28; 95% confidence interval, 0.15-0.54) compared with those consuming <100 IU/d and <750 mg/d. Increases in vitamin D and calcium intakes were associated with decreases in breast densities, suggesting that dietary vitamin D and calcium could reduce breast cancer risk possibly through influences on breast tissue morphology.

Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women.

BACKGROUND: Vitamin D status, determined on the basis of 25-hydroxyvitamin D [25(OH)D] concentrations, is associated with the risk of several diseases. Vitamin D binding protein (DBP) is the major carrier of vitamin D and its metabolites, but the role of DBP single nucleotide polymorphisms (SNPs) on 25(OH)D concentrations is unclear. OBJECTIVE: The objective was to evaluate the association of 2 DBP gene SNPs with 25(OH)D concentrations and explore whether such association varies according to the amount of vitamin D that needs to be transported. DESIGN: This cross-sectional study included 741 premenopausal white women, mostly of French descent. Plasma 25(OH)D concentrations were measured by radioimmunoassay. DBP-1 (rs7041) and DBP-2 (rs4588) were genotyped with a Sequenom MassArray platform. Associations and interactions were modeled by using multivariate linear regression. RESULTS: DBP-1 and DBP-2 SNPs were in strong linkage disequilibrium and were both associated with 25(OH)D concentrations. An additional copy of the rare allele of DBP-1 or DBP-2 was associated with lower 25(OH)D concentrations (beta = -3.29, P for trend = 0.0003; beta = -4.22, P for trend < 0.0001, respectively). These DBP polymorphisms explained as much of the variation in circulating 25(OH)D as did total vitamin D intake (r2 = 1.3% for DBP-1, r2 = 2.0% for DBP-2, and r2 < or = 1.2% for vitamin D intake). CONCLUSION: Circulating 25(OH)D concentrations in premenopausal women are strongly related to DBP polymorphisms. Whether DBP rare allele carriers have a different risk of vitamin D-related diseases and whether such carriers can benefit more or less from dietary interventions, vitamin D supplementation, or sun exposure need to be clarified.

Multivitamin-multimineral supplement use and mammographic breast density.

BACKGROUND: The effect of multivitamin-multimineral supplements on the occurrence of chronic diseases, such as breast cancer, is unclear. Breast density is increasingly used as a biomarker of breast cancer risk. OBJECTIVE: The present study evaluated the association of multivitamin-multimineral supplement use with breast density. DESIGN: Premenopausal (n = 777) and postmenopausal (n = 783) women were recruited at the time of screening mammography. Anthropometric measurements were taken at recruitment. Demographic characteristics, behavioral factors, and health conditions were documented by telephone interview. Diet and multivitamin-multimineral and individual vitamin and mineral supplement use were assessed with a self-administered food-frequency questionnaire. Breast density from screening mammograms was measured using a computer-assisted method. Crude and adjusted means in breast density were evaluated according to multivitamin-multimineral supplement use using generalized linear models. RESULTS: Current multivitamin-multimineral supplement use was reported by 21.7% of women (20.7% and 22.6% of premenopausal and postmenopausal women, respectively). Premenopausal women who were currently using multivitamin-multimineral supplements had higher adjusted mean breast density (45.5%) than past (42.9%) or never (40.2%) users (P for heterogeneity = 0.03, P for trend = 0.009). Of the current users, breast density was not related to duration of multivitamin-multimineral supplement use. In postmenopausal women, multivitamin-multimineral supplement use was not associated with breast density (P for heterogeneity = 0.53, P for trend = 0.40). CONCLUSION: Regular use of multivitamin-multimineral supplements may be associated with higher mean breast density among premenopausal women. The relations of multivitamin-multimineral supplement use to breast density and breast cancer risk need to be clarified.

Quantitative exploration of possible reasons for the recent improvement in breast cancer survival.

OBJECTIVE: Breast cancer mortality has been declining in many countries including Canada because of improvements in survival. This study attempts to explain observed trends in breast cancer survival with special attention given to the role of improvements in early detection and treatment. METHODS: This study is based on 4,312 women diagnosed with primary invasive breast carcinoma treated in a Canadian breast center between 1976 and 2000 and followed to the end of 2001. Observed and relative survival rates were calculated. Multivariate relative survival regression models were used to assess trends in breast cancer survival over the study period. RESULTS: The proportion of women with small tumors (< or = 10 mm) was higher in late 1990s, while that of women with regional involvement was lower compared to earlier periods. Adjuvant chemotherapy or endocrine therapy use increased steadily from 6.6% to 84.0% during the study period. Five-year relative survival rates ranged between 82.1% and 83.7% between 1976 and 1990, and increased thereafter to reach 87.6% in 1991-95, and 92.1% in 1996-2000. During the first five years after diagnosis, women diagnosed in 1991-95 and 1996-2000 experienced a reduction in breast cancer mortality of 28% (Relative Risk (RR)= 0.72; 95% CI: 0.59-0.89) and 49% (RR = 0.51; 95% CI: 0.39-0.68) respectively compared to women diagnosed in 1976-90. Improvement in breast cancer survival in 1990's could not be explained by characteristics of women, biology of the tumor, advancements in early detection and type of initial treatments. CONCLUSION: A substantial increase in breast cancer survival was observed in the 1990s but the reasons for this improvement remain elusive. Better knowledge of these reasons could help not only to further reduce the burden related to breast cancer but also the burden related to other major cancer sites.

[Breast density: a biomarker to better understand and prevent breast cancer]. / La densité mammaire: un biomarqueur pour mieux comprendre et prévenir le cancer du sein.

In Quebec, cancer is the principal cause of mortality. This epidemiologic research program includes two components. The first component takes place at the "Institut national de santé publique du Québec" and involves surveillance and evaluation of practices in oncology with the aim of providing the Quebec Ministry of Health with some of the evidence needed to determine its policies in cancer control. The second component takes place at the "Unité de recherche en santé des populations (URESP)" of Laval University and is devoted to studying the etiology and prevention of breast cancer. This paper focuses on this second research component which uses mammographic breast density as an intermediate biomarker to study the causes of breast cancer and strategies to prevent it. Breast cancer risk is much higher among women with very dense breasts than among those with little or no breast density. Recently, we were among the first to show that women with high vitamin D or calcium intakes have less breast density than those with low intakes, especially among premenopausal women. Furthermore, we have confirmed that breast density was increased among premenopausal women with high levels of IGF-I and low levels of IGFBP3 which is consistent with the observed effect of these molecules on breast cancer risk. Studies are now being conducted to assess whether breast density varies according to blood levels of vitamin D and of additional growth factors, as well as to genetic polymorphisms involved in the pathways of vitamin D, calcium and growth factors. The increase in vitamin D and calcium intakes may prove to be a safe and inexpensive approach to breast cancer prevention; this possibility should be carefully examined as quickly as possible.