The influence of metabolic factors and ethnicity on breast cancer risk, treatment and survival: The Oslo ethnic breast cancer study

Background - Breast cancer risk remains higher in high-income compared with low-income countries. However, it is unclear to what degree metabolic factors influence breast cancer development in women 30 years after immigration from low- to a high-incidence country. Methods - Using Cox regression models, we studied the association between pre-diagnostic metabolic factors and breast cancer development, and whether this association varied by ethnicity among 13,802 women participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnic background was assessed and pre-diagnostic metabolic factors (body mass index, waist:hip ratio, serum lipids and blood pressure) were measured. A total of 557 women developed invasive breast cancer, and these women were followed for an additional 7.7 years. Results - Among women with an unfavorable metabolic profile, women from south Asia, compared with western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18–4.49). Compared with the western European women, the ethnic minority women were more likely to present with triple-negative breast cancer (TNBC) (OR 2.11, 95% CI 0.97–4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08–0.82). Among TNBC women, above-median triglycerides:HDL-cholesterol (>0.73) levels, compared with below-median triglycerides:HDL-cholesterol (≤0.73) levels, was associated with 2.9 times higher overall mortality (HR 2.88, 95% CI 1.02–8.11). Conclusions - Our results support the importance of metabolic factors when balancing breast cancer prevention and disease management among all women, and in particular among non-western women migrating from a breast cancer low-incidence to a high-incidence country

Exploring the effects of lifestyle on breast cancer risk, age at diagnosis, and survival: the EBBA-Life study

Purpose - Whether an unfavorable lifestyle not only affects breast cancer risk, but also influences age at onset of breast cancer and survival, is under debate. Methods - In a population-based cohort, the Energy Balance and Breast Cancer Aspects throughout life (EBBA-Life) study, a total of 17,145 women were included. During follow-up, 574 women developed invasive breast cancer. Breast cancer cases were followed for an additional 9.1 years. Detailed medical records were obtained. Cox’s proportional hazard regression models were used to study the association between pre-diagnostic lifestyle factors (weight, physical activity, alcohol use, smoking, and hypertension), breast cancer risk, age at diagnosis, and survival. Results - At study entry, 34.3% of the participating women were overweight and 30.7% were physically inactive. Mean age at breast cancer diagnosis was 58.0 years, and 78.9% of the tumors were estrogen receptor positive. Among menopausal women who did not use hormone therapy and had an unfavorable lifestyle (3–5 unfavorable factors), compared with women who had a favorable lifestyle, we observed a twofold higher risk for postmenopausal breast cancer (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.23–3.69), and they were 3.4 years younger at diagnosis (64.8 versus 68.2 years, P = 0.032). Breast cancer patients with an unfavorable lifestyle, compared with patients with a favorable lifestyle, had almost a two times higher overall mortality risk (HR 1.96, 95% CI 1.01–3.80). Conclusions - Our study supports a healthy lifestyle improving breast cancer prevention, postponing onset of disease, and extending life expectancy among breast cancer patients

State injury profile for Georgia

Estrogen and progesterone are key factors in the development of breast cancer, but it remains unclear whether these hormones are associated with mammographic density phenotypes in premenopausal women. We measured percent mammographic density, nondense area, and absolute mammographic density using computer-assisted breast density readings (Madena) from digitized mammograms taken on a scheduled day of the menstrual cycle (day 7–12) among 202 healthy, premenopausal women (Energy Balance and Breast cancer Aspects Study-I). Daily salivary concentrations of 17β-estradiol and progesterone throughout an entire menstrual cycle and fasting morning serum concentrations of hormones on 3 specific days of the menstrual cycle were assessed. Salivary and serum 17β-estradiol and progesterone were positively associated with percent mammographic density, we observed by 1 SD increase in overall salivary estradiol (β-value equal to 2.07, P=0.044), luteal salivary progesterone (β-value equal to 2.40, P=0.020). Women with above-median percent mammographic density had a 20% higher mean salivary 17β-estradiol level throughout the menstrual cycle. The odds ratio for having above-median percent mammographic density (>28.5%) per 1 SD increase in overall salivary 17β-estradiol was 1.66 (95% confidence interval 1.13–2.45). Women in the top tertile of the overall average daily 17β-estradiol concentrations had an odds ratio of 2.54 (confidence interval 1.05–6.16) of above-median percent mammographic density compared with women in the bottom tertile. Our finding of a relationship between estrogen, progesterone, and percent mammographic density and not with other mammographic density phenotypes in premenopausal women is biologically plausible, but needs to be replicated in larger studies

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women

Background: Mammographic density represents epithelial and stromal proliferation, while Insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, growth hormone (GH) and estrogen, may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear. Material and methods: Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast cancer Aspects (EBBA)-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen and percent mammographic density, were studied in regression models. Results: Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8%. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17β–estradiol, was associated with a higher odds for having higher percent mammographic density (>28.5 %). The odds ratios (ORs) per standard deviation increase of 17β-estradiol, were 1.81 (95% confidence interval [CI] 1.08-3.03) in the high IGF-1 stratum, and 2.08 (95% CI 1.10-3.94) in the high GH stratum. Furthermore, women in this strata of growth factors (above median) who had an overall average 17β–estradiol above median (>16.8 pmol/l), had higher ORs for having higher percent mammographic density (>28.5%): IGF-1 4.13 (95% CI 1.33-12.83), and GH 4.17 (95% CI 1.41-12.28). Conclusion: Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, of potential clinical relevance.Anthropolog

Alcohol consumption, endogenous estrogen and mammographic density among premenopausal women

Introduction: Alcohol consumption may promote aromatization of androgens to estrogens, which may partly explain the observations linking alcohol consumption to higher breast cancer risk. Whether alcohol consumption is associated with endogenous estrogen levels, and mammographic density phenotypes in premenopausal women remains unclear. Methods: Alcohol consumption was collected by self-report and interview, using semi quantitative food frequency questionnaires, and a food diary during seven days of a menstrual cycle among 202 premenopausal women, participating in the Energy Balance and Breast Cancer Aspects (EBBA) study I. Estrogen was assessed in serum and daily in saliva across an entire menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms taken between days 7–12 of the menstrual cycle. Multivariable regression models were used to investigate the associations between alcohol consumption, endogenous estrogen and mammographic density phenotypes. Results: Current alcohol consumption was positively associated with endogenous estrogen, and absolute mammographic density. We observed 18 % higher mean salivary 17β-estradiol levels throughout the menstrual cycle, among women who consumed more than 10 g of alcohol per day compared to women who consumed less than 10 g of alcohol per day (p = 0.034). Long-term and past-year alcohol consumption was positively associated with mammographic density. We observed a positive association between alcohol consumption (past year) and absolute mammographic density; high alcohol consumers (≥7 drinks/week) had a mean absolute mammographic density of 46.17 cm2 (95 % confidence interval (CI) 39.39, 52.95), while low alcohol consumers (32.4 cm2), compared to low (<1 drink/week) alcohol consumers. Conclusion: Alcohol consumption was positively associated with daily endogenous estrogen levels and mammographic density in premenopausal women. These associations could point to an important area of breast cancer prevention. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0620-1) contains supplementary material, which is available to authorized users

Validation of repeated self-reported n-3 PUFA intake using serum phospholipid fatty acids as a biomarker in breast cancer patients during treatment

Background The role of n-3 polyunsaturated fatty acids (PUFAs) in breast cancer is not clear and under debate. To explore this relationship it is important to have proper validated dietary assessment methods for measuring the intake of n-3 PUFAs. The aim of the current study is to validate two different methods used to assess the intake of selected n-3 PUFAs as well as food sources of long-chained n-3 PUFAs. Also, we aim to study how stable the intake of fatty acids is during breast cancer treatment. Methods The study-population was patients with breast cancer (Stages I-II) or ductal carcinoma in situ (DCIS-grade III) undergoing treatment (n = 49) in Norway. Dietary intake was assessed by two self-administered methods, a 256 food item food frequency questionnaire (FFQ) and a 7-day pre-coded food diary (PFD). The FFQ was administered presurgery and twelve months postsurgery, and the PFD was administered shortly after surgery (10 +/− 2 days), six and twelve months postsurgery. Fasting blood samples (presurgery, six and twelve months postsurgery) were analysed for serum phospholipid fatty acids, a biomarker for intake of n-3 PUFAs. Results Mean (SD) age was 54.2 (7.8) years at diagnosis, and the mean (SD) body mass index (BMI) was 24.8 (3.4) kg/m2. Correlation coefficients between dietary intakes of n-3 PUFAs measured with the FFQ and the PFD ranged from 0.35 to 0.66. The correlation coefficients between the PFD and the biomarker (serum phospholipid n-3 PUFAs) as well as between the FFQ and the biomarker demonstrated stronger correlations twelve months after surgery (ρ 0.40–0.56 and 0.36–0.53, respectively) compared to around surgery (ρ 0.08–0.20 and 0.28–0.38, respectively). The same pattern was observed for intake of fatty fish. The intake of n-3 PUFAs did not change during treatment assessed by the FFQ, PFD or biomarker. Conclusion These results indicate that the FFQ and the PFD can be used to assess dietary intake of fish and n-3 PUFAs in breast cancer patients during breast cancer treatment. Still, the PFD shortly after surgery should be used with caution. The diet of patients undergoing breast cancer treatment was quite stable, and the intake of n-3 PUFAs did not change

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

Background: High-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear. Methods: Among 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35–75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics. Results: The breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m2; total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5 %. Most (93 %) of the patients had estrogen receptor (ER) positive tumors (≥1 % ER+), and 82 % had progesterone receptor (PgR) positive tumors (≥10 % PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22–0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51–1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28–4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36–1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1’s contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No association was observed between lipoproteins and ER expression. Conclusion: Our findings hypothesize associations between different lipoprotein subfractions, and PgR expression, and Ki 67 % in breast tumors. These findings may have clinical implications, but require confirmation in larger studies

Lipoprotein subfractions by nuclear magnetic resonance are associated with tumor characteristics in breast cancer

Background: High-Density Lipoprotein (HDL)-cholesterol, has been associated with breast cancer development, but the association is under debate, and whether lipoprotein subfractions is associated with breast tumor characteristics remains unclear. Methods: Among 56 women with newly diagnosed invasive breast cancer stage I/II, aged 35–75 years, pre-surgery overnight fasting serum concentrations of lipids were assessed, and body mass index (BMI) was measured. All breast tumors were immunohistochemically examined in the surgical specimen. Serum metabolomics of lipoprotein subfractions and their contents of cholesterol, free cholesterol, phospholipids, apolipoprotein-A1 and apolipoprotein-A2, were assessed using nuclear magnetic resonance. Principal component analysis, partial least square analysis, and uni- and multivariable linear regression models were used to study whether lipoprotein subfractions were associated with breast cancer tumor characteristics. Results: The breast cancer patients had following means: age at diagnosis: 55.1 years; BMI: 25.1 kg/m2 ; total-Cholesterol: 5.74 mmol/L; HDL-Cholesterol: 1.78 mmol/L; Low-Density Lipoprotein (LDL)-Cholesterol: 3.45 mmol/L; triglycerides: 1.18 mmol/L. The mean tumor size was 16.4 mm, and the mean Ki67 hotspot index was 26.5 %. Most (93 %) of the patients had estrogen receptor (ER) positive tumors (≥1 % ER+), and 82 % had progesterone receptor (PgR) positive tumors (≥10 % PgR+). Several HDL subfraction contents were strongly associated with PgR expression: Apolipoprotein-A1 (β 0.46, CI 0.22–0.69, p < 0.001), HDL cholesterol (β 0.95, CI 0.51–1.39, p < 0.001), HDL free cholesterol (β 2.88, CI 1.28–4.48, p = 0.001), HDL phospholipids (β 0.70, CI 0.36–1.04, p < 0.001). Similar results were observed for the subfractions of HDL1-3. We observed inverse associations between HDL phospholipids and Ki67 (β -0.25, p = 0.008), and in particular between HDL1’s contents of cholesterol, phospholipids, apolipoprotein-A1, apolipoprotein-A2 and Ki67. No association was observed between lipoproteins and ER expression. Conclusion: Our findings hypothesize associations between different lipoprotein subfractions, and PgR expression, and Ki 67 % in breast tumors. These findings may have clinical implications, but require confirmation in larger studie