<div>Abstract<p>Dietary composition can influence systemic inflammation; higher levels of circulating inflammatory biomarkers are associated with increased risk of breast and other cancers. A total of 438 overweight/obese, healthy, postmenopausal women were randomized to a caloric-restriction diet (goal: 10% weight-loss), aerobic-exercise (225 min/week moderate-to-vigorous activity), combined diet+exercise, or control. Dietary inflammatory index (DII) and energy-adjusted (E-DII) scores were derived from food frequency questionnaires (FFQ) and could be calculated for 365 participants with complete FFQs at baseline and 12 months. Changes from baseline to 12 months in E-DII scores in the intervention arms versus controls were analyzed using generalized estimating equations, adjusted for confounders. We examined associations between changes in previously measured biomarkers and E-DII at 12 months. Participants randomized to diet and diet+exercise arms had greater reductions in E-DII (−104.4% and −84.4%), versus controls (−34.8%, both <i>P</i> < 0.001). Weight change had a more marked effect than E-DII change on biomarkers at 12-months; associations between E-DII and biomarker changes were reduced after adjustment by weight change. Changes in E-DII at 12 months, adjusted for weight change, were negatively associated with changes in ghrelin [<i>r</i> = −0.19; <i>P</i> = 0.05 (diet), <i>r</i> = −0.29; <i>P</i> = 0.02 (diet+exercise)], and positively with VEGF [<i>r</i> = 0.22; <i>P</i> = 0.03 (diet+exercise)], and red blood cell counts [<i>r</i> = 0.30; <i>P</i> = 0.004 (exercise)]. C-reactive protein (CRP) and IL6 levels were not associated with E-DII changes at 12 months. In conclusion, a behavior change of low-calorie, low-fat diet significantly reduces dietary inflammatory potential, modulating biomarkers that are associated with tumorigenesis, such as VEGF, but not CRP or IL6.</p>Prevention Relevance:<p>Diets high in saturated fats and low in fruit and vegetable intake are associated with increased inflammation, which increases cancer risk. This study showed that changes in diet quality had effects on factors associated with cancer; however, the majority of beneficial effects were associated with weight loss rather than diet quality.</p></div>
High triglycerides and low levels of high density lipoprotein (HDL)-cholesterol are observed to promote tumor growth. However, whether breast cancer heterogeneity may explain the contradictory influence of triglycerides and cholesterol observed on breast cancer prognosis remains unclear. A population-based survival study among 464 breast cancer cases identified within the Tromsø study was conducted. Pre-diagnostic triglycerides, total-cholesterol and HDL-cholesterol were measured, and detailed clinical and histopathological data were obtained. Using tissue microarray, all breast cancer cases were reclassified into the following subtypes: Luminal A, Luminal B, HER2-enriched, and triple negative breast cancer (TNBC). Multivariable Cox proportional hazards regression models were used to study the associations between pre-diagnostic lipids and breast cancer recurrence, mortality, and survival. A total of 464 breast cancer patients, with mean age at diagnosis of 57.9 years, were followed for a mean 8.4 years. TNBC patients in the highest tertile of triglycerides (≥ 1.23 mmol/l) had 3 times higher overall mortality compared to TNBC patients in the lowest tertile (≤ 0.82 mmol/l) (HR 2.99, 95% CI 1.17–7.63), and the 5-year overall survival was 19% lower for TNBC patients in the highest vs. lowest tertile of triglycerides (65% vs. 84%). TNBC patients in the highest tertile of the HDL-cholesterol/total-cholesterol ratio (≥0.35), compared to those in the lowest tertile (≤0.27), had a 67% reduced overall mortality risk (HR 0.33, 95% CI 0.12–0.89). No associations were observed between lipids and prognostic outcome among breast cancer patients overall, or among patients with luminal A and luminal B subtypes. Among HER2-enriched patients, pre-diagnostic triglyceride level was inversely associated with overall mortality. Our study suggests that pre-diagnostic triglycerides and the HDL-cholesterol/total-cholesterol ratio may independently provide unique information regarding prognostic outcome among triple negative breast cancer patients. However, a small sample size underlines the need for additional studies.
Abstract Reproductive and menstrual characteristics, as well as high circulating estrogen concentrations, are associated with risk of hormone-related cancers in postmenopausal women. To explore possible etiologic relationships between menstrual/reproductive characteristics and risk of hormone-related cancers, we examined associations between menstrual/reproductive factors and serum concentrations of free estradiol, total estradiol, estrone, sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH). This study was conducted in 173 postmenopausal women using data from the prerandomization visit of an exercise clinical trial. Participants were sedentary, overweight/obese, and not on hormone therapy. Women ≥20 years past menopause had 23% lower total estradiol and 30% lower free estradiol concentrations than women within 4 years of menopause (P for trend = 0.04 and 0.02, respectively). Nulliparous women had 19% higher FSH concentrations than parous women (P = 0.02). Among parous women, parity was positively associated with SHBG and negatively associated with free estradiol concentrations. Women with ≥4 children had 20% lower free estradiol and 38% higher SHBG concentrations compared with women with one birth (P for trend = 0.02 and 0.01, respectively). Total number of months spent breast-feeding was modestly and inversely associated with serum FSH concentrations (P for trend = 0.07). Our results suggest that menstrual/reproductive characteristics may be associated with postmenopausal hormone concentrations; verification of these results in other studies may elucidate how these variables influence risk of hormone-related cancers.
Women who are physically active have a decreased risk for breast cancer, but the types, amounts, and timing of activity needed are unknown.To prospectively examine the association between current and past recreational physical activity and incidence of breast cancer in postmenopausal women.Prospective cohort study in 74 171 women aged 50 to 79 years who were recruited by 40 US clinical centers from 1993 through 1998.Incident invasive and in situ breast cancer.We documented 1780 newly diagnosed cases of breast cancer over a mean follow-up of 4.7 years. Compared with less active women, women who engaged in regular strenuous physical activity at age 35 years had a 14% decreased risk of breast cancer (relative risk [RR], 0.86; 95% confidence interval [CI], 0.78-0.95). Similar but attenuated findings were observed for strenuous physical activity at ages 18 years and 50 years. An increasing total current physical activity score was associated with a reduced risk for breast cancer (P =.03 for trend). Women who engaged in the equivalent of 1.25 to 2.5 hours per week of brisk walking had an 18% decreased risk of breast cancer (RR, 0.82; 95% CI, 0.68-0.97) compared with inactive women. Slightly greater reduction in risk was observed for women who engaged in the equivalent of 10 hours or more per week of brisk walking. The effect of exercise was most pronounced in women in the lowest tertile of body mass index (BMI) (<24.1), but also was observed for women in the middle tertile of BMI (24.1-28.4).These data suggest that increased physical activity is associated with reduced risk for breast cancer in postmenopausal women, longer duration provides most benefit, and that such activity need not be strenuous.
Abstract Mammographic density (MD) is positively associated with breast cancer risk and with breast cancer recurrence. Factors that influence MD include age, circulating endogenous hormone levels, hormone therapy, menopausal status, parity, adiposity, and genetic variation. The association between MD and estrogen levels may be regulated to an extent by the immune system. Cytokines such as IL-6 influence aromatase activity and therefore estrogen synthesis. Experiments on breast cancer cell lines have shown that IL-6, in combination with estrone sulfate enhances cellular proliferation through their action on aromatase. Acute phase proteins C-Reactive Protein (CRP) and Serum Amyloid A (SAA) are nonspecific inflammatory markers that increase with systemic inflammation in response to elevated levels of IL-6. The purpose of this study is to evaluate whether CRP or SAA are associated with MD among postmenopausal women who are breast cancer survivors. Circulating levels of CRP, SAA, and percent MD approximately 30 months after diagnosis were obtained from 479 women participating in the Health, Eating, Activity, and Lifestyle Study (HEAL). HEAL is a prospective cohort study of 1,183 breast cancer survivors identified through Surveillance, Epidemiology, and End Results registries in Los Angeles County, New Mexico, and Western Washington. For this analysis, regression models were used to estimate associations between CRP/SAA and MD after adjustments for age, race, body mass index (BMI), post-menopausal hormone use, tamoxifen use, and study center. Potential effect modification by factors that could influence inflammation or estrogen levels was evaluated by stratification and with formal tests of interaction. After adjusting for covariates, we found a negative association between CRP and MD (β=-0.13, p=0.03) and no association between SAA and MD (β=-0.09, p=0.31). These associations were not modified by race, use of non-steroidal anti-inflammatory drug, smoking, or physical activity. Further, we found that women with CRP levels that were lower than the median (<2.4 CRP mg/L) had higher geometric mean percent MD than women at or above the median; this association was consistent across 5-year age groups. The largest association between CRP and MD was found among women <50 years of age (β=-0.33, p=.01) although there was no statistically significant interaction between CRP and age. Our results suggest CRP is inversely associated with MD after adjusting for BMI and other covariates. These findings should be confirmed in independent disease free population that includes direct measures of cytokine activity such as IL-6. Additional exploration of biological mechanism is needed. Citation Format: Anne Dee, Roberta McKean-Cowdin, Anne McTiernan, Richard N. Baumgartner, Kathy B. Baumgartner, Rachel Ballard-Barbash, Leslie Bernstein. Acute-phase proteins (C-reactive protein and Serum Amyloid A) and post-diagnosis mammographic density in breast cancer survivors. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B87.
Abstract Background C-reactive protein (CRP) and Serum amyloid A protein (SAA) increases with systemic inflammation and are related to worse survival for breast cancer survivors. This study examines the association between percent body fat and SAA and CRP and the potential interaction with NSAID use and weight change. Methods Participants included 134 non-Hispanic white and Hispanic breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Body fat percentage, measured with Dual Energy X-ray Absorptiometer (DEXA), and circulating levels of CRP and SAA were obtained 30 months after breast cancer diagnosis. Results Circulating concentrations of CRP and SAA were associated with increased adiposity as measured by DEXA after adjustment for age at 24-months, race/ethnicity, dietary energy intake, weight change, and NSAID use. Survivors with higher body fat ≥35% had significantly higher concentrations of CRP (2.01 mg/l vs. 0.85 mg/l) and SAA (6.21 mg/l vs. 4.21 mg/l) compared to non-obese (body fat < 35%). Women who had gained more than 5% of their body weight since breast cancer diagnosis had non-statistically significant higher geometric mean levels of CRP and SAA. Mean levels of CRP and SAA were higher among obese women who were non-users of NSAIDs compared to current users; the association with SAA reached statistical significance (Mean SAA = 7.24, 95%CI 6.13-8.56 for non-NSAID; vs. 4.87; 95%CI 3.95-6.0 for NSAID users respectively). Conclusions Breast cancer survivors with higher body fat had higher mean concentrations of CRP and SAA than women with lower body fat. Further assessment of NSAID use and weight control in reducing circulating inflammatory markers among survivors may be worthwhile to investigate in randomized intervention trials as higher inflammatory markers are associated with worse survival.
'%3e%3cpath fill='%23001489' d='M0 0v6h9V0z'/%3e%3cpath fill='%23e03c31' d='M0 0v3h9V0z'/%3e%3cg stroke='%23fff' stroke-width='2'%3e%3cpath id='d' d='m0 0 4.5 3L0 6m4.5-3H9'/%3e%3cuse xlink:href='%23b' stroke='%23ffb81c' clip-path='url(%23c)'/%3e%3c/g%3e%3cuse xlink:href='%23d' fill='none' stroke='%23007749' stroke-width='1.2'/%3e%3c/g%3e%3c/svg%3e)