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/m(2); 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 (ß 0.46, CI 0.22-0.69, p < 0.001), HDL cholesterol (ß 0.95, CI 0.51-1.39, p < 0.001), HDL free cholesterol (ß 2.88, CI 1.28-4.48, p = 0.001), HDL phospholipids (ß 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 (ß -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.

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, insulin-like growth factor-binding protein-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. MATERIALS AND METHODS: Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-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 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 17ß-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5%). The odds ratios (ORs) per standard deviation increase in 17ß-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 these strata of growth factors (above median) who had an overall average 17ß-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, and may be of potential clinical relevance.

Duration of lactation, maternal metabolic profile, and body composition in the Norwegian EBBA I-study.

OBJECTIVE: There is conflicting evidence as to whether duration of lactation may decrease the risk of subsequent development of an unfavorable maternal metabolic profile, including overweight and obesity. We hypothesized that duration of lactation is associated with a more favorable metabolic profile and healthier anthropometric measurements. SUBJECTS AND METHODS: Ninety-eight parous women were studied from the Norwegian EBBAI-study (Energy Balance and Breast cancer Aspects-study), a cross-sectional study of healthy premenopausal women 25-35 years old. Historical lactation data were collected, anthropometric measurements were taken, fasting blood samples (for serum glucose, triglycerides, total cholesterol, and high-density lipoprotein cholesterol) were drawn, and women were asked to fill in a precoded food diary. RESULTS: Mean time since last birth was 4.7 years, mean number of children was 1.9, mean total duration of lactation was 19 months, and average length of lactation per child was 10.3 months. Women who on average lactated for less than 10 months per child had higher mean levels of fasting serum glucose (5.2 mmol/L vs. 5.0 mmol/L, p=0.04), serum triglyceride (0.91 mmol/L vs. 0.66 mmol/L, p=0.001), and serum cholesterol (4.78 mmol/L vs. 4.32 mmol/L, p=0.004) and a higher waist-to-hip ratio (0.81 vs. 0.77, p=0.001) than women who lactated for 10 months or more per child. The inverse association between average length of lactation per child and waist-to-hip ratio persisted after adjustment for potential confounders. CONCLUSIONS: These results support the hypothesis that duration of lactation may be associated with a healthier metabolic profile and healthier anthropometric measurements, especially lipid levels and waist-to-hip ratio, even years after weaning.