Nut intake has been associated with reduced mortality and risk of cardiovascular diseases, but there is only limited evidence on cancer. We investigated the relationship between nut intake and risk of postmenopausal breast cancer, and estrogen/progesterone receptor (ER/PR) subtypes.In The Netherlands Cohort Study, 62,573 women aged 55–69 years provided information on dietary and lifestyle habits in 1986. After 20.3 years of follow-up, 2,321 incident breast cancer cases and 1,665 subcohort members were eligible for multivariate case-cohort analyses.p trend = 0.025). There were no significant inverse associations with ER + or total breast cancer. While there was no variation between PR subtypes, the ER–PR- subtype was also significantly inversely associated with nut intake, with HR 0.53 (95% CI 0.29–0.99), p trend = 0.037. Intake of peanuts and tree nuts separately was also inversely related to ER − breast cancer subtypes, while no associations were found with peanut butter intake.Total nut intake was significantly inversely related to ER negative (ER −) breast cancer risk, with HR 0.55 (95% CI 0.33–0.93) for those consuming at least 10 g nuts/day versus non-consumers  contains supplementary material, which is available to authorized users. Nut intake has been associated with reduced risk of non-communicable diseases such as cardiovascular diseases (CVD) and diabetes . Apart fFor breast cancer, two cohort studies have investigated the association between nut intake and breast cancer risk , 7; bothIt is important to distinguish between pre- and postmenopausal breast cancer, as well as estrogen/progesterone receptor (ER/PR) subtypes, because of differences in etiology.We investigated the association between intakes of total nuts, tree nuts, peanuts, and peanut butter, and postmenopausal breast cancer risk, overall and stratified by hormone receptor status, in The Netherlands Cohort Study (NLCS). We recently found an inverse association between Mediterranean Diet (MD)-adherence and ER − breast cancer in the NLCS , in whicn = 2589 women), randomly sampled from the cohort immediately after baseline. These subcohort members were actively followed up biennially for vital status information. The follow-up of the subcohort was 100% complete at 20.3 years of follow-up.The NLCS started in September 1986 and the female part included 62,573 women aged 55–69 years . At baseFollow-up for cancer incidence in the entire cohort was established by annual record linkage with The Netherlands Cancer Registry and PALGA, the nationwide Dutch Pathology Registry . CompletThe 11-page baseline questionnaire measured dietary intake, detailed smoking habits, anthropometry, physical activity, and other risk factors related to cancer . HabituaFor the intakes of nuts and peanut butter, the mean (SD) values were calculated in the subcohort. The distribution of the subcohort members by nut intake level and various characteristics was examined by cross-tabulations and summary statistics.The relationship between intake of nuts and breast cancer risk was evaluated using Cox proportional hazards models. It was verified that the proportional hazards assumption was not violated using Schoenfeld residuals  and − ln2), non-occupational physical activity , highest level of education , family history of breast cancer in mother or sisters , history of benign breast disease , age at menarche , parity , age at first birth , age at menopause , oral contraceptive use , postmenopausal hormone replacement therapy , energy intake , alcohol intake . Because we recently found an association between Mediterranean diet adherence and breast cancer risk . For the ER − subtype, inverse associations were seen in most subgroups, and there was no significant interaction with these covariables. Possible interactions with age at baseline , smoking status , and family history of breast cancer  were also investigated, but were all non-significant.In Fig. In this large prospective study, we found a statistically significant inverse association between nut intake and risk of estrogen receptor-negative postmenopausal breast cancer. There were no significant inverse associations with ER + or total breast cancer risk. When comparing those consuming 10 + g nuts/day to non-consumers, the HR for ER − breast cancer was 0.55, while it was 0.91 for total breast cancer and 1.07 for ER + breast cancer. While there was no variation between PR subtypes, the ER–PR − subtype was also significantly inversely associated with nut intake. There was no statistical evidence of non-linear dose–response relationships, but this non-linearity test was borderline significant for ER − breast cancer, where the exposure–response curves show a clear leveling off with intake levels above 10 g/day. Intake of peanuts and tree nuts separately was also inversely related to ER − breast cancer subtypes, while no associations were found with peanut butter intake. There was significant interaction between total nut intake and BMI for total breast cancer and ER + breast cancer risk.The PREDIMED randomized controlled trial in Spain investigated whether following a Mediterranean diet supplemented with nuts compared to a control diet in which it was advised to decrease dietary fat reduced the risk of breast cancer . After aIn two cohort studies, the relationship between nut consumption and risk of breast cancer was studied. Sonestedt et al.  in SwedeBesides these cohort studies, six case–control studies on this topic were identified. A case–control study in Argentina found non-significantly increased breast cancer risks with higher nut  consumption when comparing cases to both hospital and neighborhood controls . An ItalTwo cohort studies were performed on nut intake and risk of benign breast disease, both in the US. Su et al.  found a Thus, the literature is mixed with null results in two cohort studies and inverse and positive associations in case–control studies (which may be linked to storage conditions of nuts in developing countries), but very few studies have investigated hormone receptor subtypes.We also found no association with total breast cancer, but did find an inverse association with ER − subtypes. This needs to be confirmed in other large cohort studies and trials, with analyses per receptor subtype. We did not have data on nut intake in adolescence or early adulthood, which might be etiologically relevant; future studies might also focus on that.In the NLCS, we earlier reported inverse associations with MD adherence in the ER − subtypes . In the Although nuts have a high fat content, they contain mainly monounsaturated (MUFA) or polyunsaturated fatty acids (PUFA), and are very low in saturated fat . When coThe prospective design and high completeness of follow-up of the NLCS make information bias and selection bias unlikely. A potential weakness is the moderate proportion of breast cancer cases for whom ER/PR status was known. Breast cancer cases with known and unknown receptor status did not differ importantly according to baseline and tumor characteristics, making selection bias of the cases unlikely (data not shown). Although many possible confounders were taken into account, the possibility of confounding by unmeasured factors remains. The validation study of the food frequency questionnaire has shown that it performs relatively well , but meaIn conclusion, our cohort study showed a statistically significant inverse association between total nut intake and risk of ER − breast cancer. There were no significant inverse associations with ER + or total breast cancer risk. While there was no variation between PR subtypes, the ER–PR − subtype was also significantly inversely associated with nut intake. For ER − breast cancer, the exposure–response curves using restricted cubic splines showed a clear leveling off with intake levels above 10 g/day, but the non-linearity test was not significant. Intake of peanuts and tree nuts separately was also inversely related to ER − breast cancer subtypes, while no associations were found with peanut butter intake.Below is the link to the electronic supplementary material.Flow diagram of the number of subcohort members and cancer cases on which analyses are based, Netherlands Cohort Study. (DOCX 48 KB)


Studies have shown that morbidity and mortality rates due to cancer among recent immigrants are lower than those among the native-born population. The objectives of this study were to describe the incidence of colorectal and breast cancer among immigrants from major regions of the world compared to Canadian-born residents of the province of Ontario and to examine the role of length of stay and neighborhood income.Retrospective cohort study including all individuals 18 years and over residing in Ontario from 2004 to 2014. Age-standardized incidence rates (ASIR) were calculated for immigrants from each world region versus Canadian-born residents and stratified by neighborhood income quintile and length of stay. Binomial regression analysis was used to determine the association of neighbourhood income, length of stay, and location of birth with colorectal and breast cancer incidence.Canadian immigrants born in South Asia had the lowest colorectal and breast cancer incidence  compared to long-term residents during the study period . In multivariate analyses, neighboorhood income did not consistently play a significant role in colorectal cancer incidence; however higher neighbourhood income was a risk factor for breast cancer among immigrant women . Increased length of stay was associated with higher risk of cancer. After adjusting for age, neighborhood income, and length of stay, those born in Europe and Central Asia had the highest risk of colorectal cancer compared to those born in East Asia and Pacific and those born in the Middle East had the greatest additional risk of breast cancer.After correcting for age, breast and colorectal cancer incidence rates among immigrants differ according to their region of birth and recent immigrants to Ontario have lower colorectal and breast cancer incidence rates than their native-born peers. However, those advantages diminish over time. These findings call for Ontario to generate tools and interventions to maintain the health of the immigrant population, particularly for those groups with a higher incidence of cancer. Immigrants represent a large, increasing and vital segment of the Canadian population. Most Canadian studies have shown that morbidity and mortality rates of chronic disease among recent immigrants are lower than those among the general Canadian population suggesting that immigrants enjoy the “healthy immigrant effect” whereby they are in better physical condition on arrival than host country inhabitants as a result of selective migration –4.Ontario, the largest province in Canada, has a large and diverse immigrant population and approximately one-third of the population in Ontario is foreign-born . OntarioColorectal cancer is the third most common cancer diagnosed in men and women with 26,800 cases per year in Ontario. Breast cancer is the most common cancer among women with 26,300 cases a year in Ontario . Also, cThe following datasets were linked using unique encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES). The Registered Persons Database was used to identify people aged 18 years and over in the province of Ontario eligible for health care. The Registered Persons Database contains basic demographic information for those who have ever received an Ontario health card number for the province’s universal health care system . All citizens and permanent residents are eligible for health care. The second database was the Immigration Refugee and Citizenship Canada (IRCC) Database . The CanUsing the postal-code conversion file , ecologiThe age-standardized annual incidence rates (ASIR) were calculated using the 2010 Canadian population as standard, for long-term residents, for immigrants, and then by world region of origin for immigrants. To assess the effect of neighboorhood income and length of stay in Canada, ASIR were stratified by time since immigration 0–5 years, 6–10 years and 11+ years) and by neighborhood income quintile (1 through 5).Predictors of breast and colorectal cancer incidence among all residents in Ontario, 2004–2014 were assessed by two binomial regression models, one among the entire cohort and one among only immigrants. Among the entire cohort, predictors entered into the model included age, place of birth and neighborhood income quintile. The second model calculated among only immigrants assessed the effect of age, neighborhood income quintile, length of stay and region of birth. The analyses produced adjusted rate ratios (RR) with corresponding confidence intervals (CI). Statistical significance was determined at the 0.05 level. All analyses were conducted using SAS statistical software, version 9.4. This study was approved by the institutional review board at Sunnybrook Health Sciences Centre, Toronto, Canada.Demographic characteristics of the study population are shown in Table Age-standardized incidence rates varied by region, with long-term residents consistently having the highest rates and South Asian immigrants consistently having the lowest rates of colorectal and breast cancer Fig. . Among iASIR were also examined based on length of stay and neighborhood income quintile. We found that the ASIR were not associated with neighborhood income quintile for females and males with colorectal cancer Fig. . Standarp < 0.01) trend was found for income for colorectal cancer where risk was higher among those in lower income neighborhoods. The effect of neighborhood income on the risk of breast cancer for women was in the opposite direction with each neighborhood income quintile conferring additional risk of breast cancer , and this relationship was significant as a trend as well (p < 0.0001). After adjusting for age and neighborhood income, those born in Europe and Central Asia had the greatest additional risk of colorectal cancer compared to long-term residents. Regarding breast cancer, those born in the Middle East and North Africa had the greatest additional risk of colorectal cancer compared to long-term residents. Those born in South Asia had the lowest rates of breast and colorectal cancer compared to long-term residents . After adjusting for age, neighborhood income, and length of stay, those born in Europe and Central Asia had the greatest additional risk of colorectal cancer compared to the reference group for this analysis of those born in East Asia and the Pacific. Those born in South Asia had the lowest risk for colorectal cancer among males and females and of breast cancer compared to those born in East Asia and the Pacific  and those from South Asia having the lowest rates . Those from the Middle East and North Africa were at highest risk among immigrant women to develop breast cancer (incidence = 1.49) and those from South Asia were the lowest (incidence- = 1.00). Third, we saw that neighborhood income did not play a role in colorectal cancer incidence but that higher neighborhood income was a risk factor for breast cancer incidence among immigrant women .Upon examining place of birth, we saw large differences (49–264% difference) in age standardized rates between places of birth. In comparison to long-term residents the largest differences were for those born in South Asia who had the lowest rates for colorectal and breast cancer. These differences are most likely attributed to differences in their home countries where South Asia has among the lowest incidence rates compared to other regions for breast and colorectal cancer . Age-staNeighborhood income did not play a significant role in colorectal cancer incidence. Those in the highest neighborhood income quintile had slightly lower rates of colorectal cancer in the regression model including all Ontario residents; however, no effect was seen when examining rates among only immigrants. In contrast, we saw that higher neighborhood income was a risk factor for breast cancer incidence, both unadjusted and in regression models. Similarly, Canadian and American data have shown that women in neighborhoods with higher neighborhood incomes have a higher risk of developing breast cancer , 15.An important dimension of the healthy immigrant effect is that the immigrant advantage we found appeared to disappear after spending over 10 years in Canada for both colorectal and breast cancer incidence. In addition, in the regression model limited to immigrants we saw that risk of cancer increases (5–7%) for each additional five years in Canada for both colorectal and breast cancer. Similarly, researchers have previously found that among Ontarian immigrants, despite the original advantage with immigration, there is a steady decline in survival, and cancer-specific survival, over time . AnalysiOthers maintain that worsening of health status is due to barriers to health services including lack of familiarity with the Canadian health system and language or cultural differences  that mayThis large cohort study has examined cancer incidence among immigrants in Canada which has not been examined since the 1990s . Due to Our analysis showed breast and colorectal cancer incidence rates among immigrants to Ontario, Canada are lower than residents and these rates differ according to region of birth, however, those advantages diminish after arrival. Results from this hypothesis-generating research initiative hold significant immigration and health policy implications, and add further intricacy to the study of the social determinants of health. The results call for Ontario to generate tools and interventions to maintain the health of immigrant population.


No scientific consensus has been reached on whether active tobacco smoking causes breast cancer. We examine the association between active smoking and breast cancer risk in Denmark, which has some of the highest smoking and breast cancer rates in women worldwide.We used the data from a nationwide Danish Nurse Cohort on 21,867 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on smoking status, onset, duration, and intensity, as well as breast cancer risk factors. We obtained data on incidence of breast cancer from Danish Cancer Registry until 2013, and used Cox regression models to analyze the association between smoking and breast cancer.Of 21,831 women (mean age 53.2 years) 1162 developed breast cancer during 15.7 years of follow-up. 33.7% of nurses were current and 30.0% former smokers at cohort baseline. Compared to never smokers, we found increased risk of breast cancer of 18% in ever  and 27% in current  smokers. We detected a dose-response relationship with smoking intensity with the highest breast cancer risk in women smoking >15 g/day  or >20 pack-years . Parous women who smoked heavily (>10 pack-years) before first childbirth had the highest risk of breast cancer . Association between smoking and breast cancer was not modified by menopausal status, obesity, alcohol or hormone therapy use, and seemed to be limited to the estrogen receptor positive breast cancer subtype.Active smoking increases risk of breast cancer, with smoking before first birth being the most relevant exposure window. Tobacco smoke is the leading cause of cancer worldwide and contains over 4000 known carcinogenic substances.  No scienRecent large prospective cohort studies –13 with In Denmark, with some of the highest smoking prevalence and breast cancer incidence in the world, the impact of smoking on breast cancer has been debated due to conflicting results from the early Danish studies. , 17 MoreThe Danish Nurse Cohort  was inspData on active tobacco smoking were obtained from the baseline questionnaire in 1993 or 1999, and included questions on smoking status (never/former/current), smoking duration (years), age at smoking onset (years), average number of cigarettes, cheerots, and cigars smoked per day, and on smoking a pipe (yes/no) in ever smokers. Based on this information we calculated smoking intensity in g/day by equating a cigarette to 1 g, a cheroot to 3 g, and a cigar to 4.5 g of tobacco, and pack-years of smoking by multiplying the number of packs per day (1 pack = 20 g) and the number of years smoked. We defined onset of smoking before and after 1st birth in parous women and age of 21 years (mean age of smoking initiation in the cohort) in nulliparous women. Pack-years of smoking before 1st childbirth, between 1st childbirth and menopause, and after menopause was calculated from information on age of smoking onset, age at 1st birth, and age at menopause in parous postmenopausal women. No information was collected on passive smoking in the Danish Nurse Cohort.We linked the records of 28,731 nurses using unique identification number to the Danish Cancer Register  to extra2; 18.5–25 kg/m2; 25–30 kg/m2; ≥30 kg/m2), alcohol use ; heavy (>15 drinks/week)), leisure time physical activity , night shift work , age at menarche (years), parity , number of children, age at first birth (years), menopausal status , HT use , and OC use . The follow-up started on the cohort baseline date (1st April 1993 or 1st April 1999) and ended at the date of breast cancer (event) or other cancer diagnoses (except non-melanoma skin cancer), death, emigration, or December 31, 2012 (censoring), whichever came first. We evaluated the effect of active smoking status, duration, intensity, and onset in separate models. We performed tests for trend by using the ordered category, including the reference as a continuous variable in the Cox model. We checked for the proportional hazards assumption for all smoking variables and confounders based on scaled Schoenfeld residuals. [We used Cox proportional hazards regression with age as the underlying time, to investigate the association between smoking and breast cancer in a crude model , and in a fully adjusted model, adjusted for age at the time of recruitment, birth cohort , Body Mass Index (BMI)  vital status and 1924 with cancer diagnosis before cohort baseline, and 4972 with missing information on one or more covariates. Of the 21,831 nurses in the main analyses 1162 developed breast cancer during the mean follow-up of 15.7 years or 342,538 person-years, with an incidence rate of 339 per 100,000 person-years.The mean age at baseline was 53.2 years, 56.7% of the women were postmenopausal, 14.5% nulliparous, and the mean age at 1st childbirth for parous women was 25.9 years (Table The majority of nurses (63.7%) were ever smokers at cohort baseline,  whilst 36.3% never smokers. 38.3% of women who developed breast cancer were current smokers at baseline, as compared to 33.4% of women who were free of breast cancer Table . Mean duWhilst smoking rates and smoking intensity were lower in younger, as compared to older birth cohorts, the age at smoking initiation decreased, from 22.6 years in women born before 1935, to 17.8 in women born 1950–55  smokers, strongest in current , and weaker in previous  smokers  than with ER-  breast cancer, compared to never smoking  in the Danish Diet, Cancer and Health cohort, which formed the Danish part of the EPIC study.  A possibWe found the highest risk of breast cancer related to smoking heavily before the 1st childbirth, in agreement with existing evidence. –8, 10–12As alcohol is an established risk factor for breast cancer, and as alcohol and smoking often come together, the possible confounding by alcohol of the effect of smoking on the risk of breast cancer has been debated in literature. Alcohol has also been previously shown to be an independent risk factor for breast cancer in the Danish Nurse Cohort.  However,We contribute with novel data on smoking and subtypes of breast cancer, as only a few studies have previously included this information. , 11, 13 Strengths of this study include data from a large prospective nationwide cohort with comprehensive follow-up of both vital status and incident breast cancer cases from linkage with nationwide registers. Exposure information from the cohort was expected to be valid as already known associations between breast cancer and, for instance, alcohol use  and HT –28 have The main limitation was the exposure misclassification as the smoking exposure was based on questionnaires at the time of recruitment, without follow-up, and the lack of information on passive tobacco smoke. However, prevalence of active and passive smoking in Denmark in this period was high, and based on data from a related Danish Diet, Cancer and Health cohort recruited in the same period, we estimated earlier that only 5% of women in this period were not exposed to passive smoke at home or work.  In any cDanish nurses have been found to live a generally healthier lifestyle than a representative sample of Danish women, as they smoked less and had higher physical activity levels, although they consumed more alcohol.  FurthermIn this cohort of Danish nurses, we found the risk of breast cancer to be almost 30% increased in current smokers as compared with never smokers. The risk increases both with smoking duration and smoking intensity. The highest risk was seen in women with more than 10 pack-years of smoking before the birth of their first child. We found no protective effect of smoking in post-menopausal age. The study contributed to the accumulating evidence for smoking - in particular in early life – as causally associated with an increased risk of breast cancer.


The risk of breast cancer is significantly increased among obese women as the deleterious adipokines can be over secreted and beneficial adipokines can be hyposecreted. We aim to evaluate the association between obesity-associated adipokines and breast cancer. We searched PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature (CBM) databases for studies reporting association of obesity related adipokines with breast cancer published before Sept. 15, 2015. Initially, 26783 publications were identified, and later, 119 articles were selected for further meta-analysis. Out of these 119 studies, twenty-six studies had reported adipokine levels among obese and non-obese healthy subjects and ninety-three studies had reported adipokine levels among patients with breast cancer. The subjects with BMI >25 kg/m2 had significantly lower adiponectin levels and higher leptin and tumor necrosis factor-α (TNF-α) levels than those with BMI <25 kg/m2. Decreased concentrations of adiponectin, and increased concentrations of leptin, IL-6, IL-8, TNF-α, resistin and visfatin were significantly associated with risk of breast cancer. Adipokine levels were strongly associated with breast cancer among Asian women as compared to non-Asian women. Our results might explain the relationship of obesity, adipokine levels and risk of breast cancer, especially in Asian women. Breast cancer is the most common cancer across the world. Approximately, 508,000 females died due to breast cancer in 2011 world over . During Adipokines, small peptide hormonal growth factors, are mainly secreted by adipocytes of white adipose tissue. Breast tissue mainly comprises of adipocytes almost 90%), and epithelial cells (rest 10% of the breast volume) 0%, and e. The dysetc.) to obesity, and to provide a reference for breast cancer biomarkers. We conducted a meta-analysis to investigate the association between adipokines, obesity and risk of breast cancer.Although over twenty adipokines are known; only twelve , lipocalin 2, IL-8, apelin and visfatin) have been implicated in breast cancer . With thin-vitro estimation, and additional eight studies were excluded because of unavailability of full text. Finally, 119 were selected for meta-analysis, twenty-six studies had compared levels of adipokines among obese and non-obese healthy subjects and ninety-three studies had evaluated among patients with breast cancer. Initially, the database search identified a total of 26783 studies. After evaluating the titles and abstracts, 26509 studies were excluded. Subsequently, 274 potentially relevant full text articles were reviewed further. Among these, 155 were excluded for the following reasons: seventy-nine studies had no or insufficient data, nine had same or overlapping data, thirteen studies had detected adipokine levels in breast tissue, thirty-eight articles were reviews, commentaries or letters, five studies included male participants, three articles had conducted The general characteristics of participants from all the included studies are presented in 2 than those with BMI < 25 kg/m2 , pooled SMD -1.19   and 1.97 , respectively  Figure . The suby Figure  and 1D. 2 Figure  and 1F. 30 kg/m2 . Subgrou30 kg/m2 .P < 0.00001) , 2.15 , 3.41 , 1.70 , 1.11 , and 1.06 , respectively  Figure . Mean coy Figure . Howevery Figure  and 2I. y Figure .P < 0.00001), but this association was not significant among non-Asians   and 1.48 , respectively , but resistin levels did not differ significantly between non-Asian cases and controls  Figure . Both Asy Figure . Similary Figure  and 3D. s Figure .P < 0.00001), 1.20 , 2.13 , 1.75 , and 1.48 , respectively , leptin  and IL-6   Figure  differed) Figure .P < 0.00001), 0.56 , 2.06  and 1.95 , respectively (P < 0.00001), 4.05  and 1.41 , respectively . Adiponectin levels were significantly lower among patients with TNM III and IV stage cancer as compared to patients of TNM I and II stage cancer . On the other hand, the mean concentration of leptin, IL-6, TNF-α and HGF were significantly higher in TNM III/IV stage patients than those of TNM I/II stage . Leptin and TNF-α levels were also significantly higher in lymph node metastasis (LNM) positive cases than in LNM negative cases, with a pooled SMD of 0.80  and 0.63  respectively. Leptin levels were significantly higher among postmenopausal cases than premenopausal cases  (I2 = 0%) (Heterogeneity tests indicated a significant heterogeneity among studies with I2 = 0%) . We alsoI2 = 0%) , suggestI2 = 0%) , suggestThis meta-analysis summarized evidence for levels of adipokines among obese and non-obese healthy subjects and the relationship between circulating adipokines and risk of breast cancer. Our findings indicate that obese subjects had lower adiponectin levels and higher leptin and TNF-α levels than non-obese subjects. We also found that decreased circulating adiponectin levels and increased leptin, IL-6, IL-8, TNF-α, resistin and visfatin levels are significantly associated with risk of breast cancer. The levels of adipokines among Asian women were more closely associated with risk of breast cancer than non-Asians. Serum concentrations of adipokines were associated with risk of breast cancer, whereas plasma concentrations of TNF-α and resistin did not differ significantly between cases and controls. Estimation by ELISA showed a significant difference between the levels of adipokines in the cases and controls, however, this difference was non-significant upon detection by Multiplex assay. The levels of adiponectin, leptin, IL-6 and TNF-α were significantly associated with higher TNM classification, and leptin levels were associated with ER and LNM positive stages and TNF-α levels were associated with LNM status.In addition to the patients with breast cancer, levels of adipokines were also evaluated among obese subjects. In comparison to non-obese subjects, circulating leptin and TNF-α levels were higher, and adiponectin levels were lower among obese persons Figure . This paIn-vitro studies indicate that leptin influences different intracellular signaling pathways including mitogen-activated protein kinase (MAPK), Janus kinase 2–signal transducer and activator of transcription 3 (JAK2–STAT3) and phosphatidylinositol 3-kinase–protein kinase B (PI3K–AKT) [In this meta-analysis we found that patients with breast cancer had significantly lower adiponectin levels than controls. It is known that adiponectin not only possesses anti-atherosclerotic, anti-inflammatory, and insulin-sensitizing properties, but it also has protective effect against cancer , 18. BarI3K–AKT) . In thisI3K–AKT) , our resTNF-α was originally identified as a polypeptide cytokine secreted by macrophages that infiltrate the adipose tissue. Plasma TNF-α concentration is positively correlated with BMI . ClinicaInterleukins are a group of cytokines produced by leukocytes. In comparison to matched normal breast tissue, breast tumors produce significantly increased levels of IL-6, and these levels also increase proportionately with higher tumor grade . PrimaryResistin, is also known as adipose tissue-specific secretory factor. It is a 12 kDa cysteine rich polypeptide found in inflammatory zone 3, and belongs to a small family of secreted protein . It is tIn vitro studies have shown that visfatin promotes cell proliferation in breast cancer via stimulation of cell cycle progression and increased expression of genes which play important roles in angiogenesis and metastasis [Visfatin plays a significant role in the nicotinamide adenine dinucelotide (NAD) dependent enzymatic activity which affects various biological responses essential for cell survival . Obese wtastasis . ConsistThis study compared for the first time, the concentrations of circulating adipokines between breast cancer patients and controls among different races. As shown in Figure In this study we found that serum levels of all adipokines were significantly associated with incidence breast cancer, whereas no association could be established with plasma levels. However, there is no explanation for this difference at this stage. These results indicate that measurement of serum adipokine levels may be a more reliable predictor of breast cancer. Circulating adipokine levels are most often measured by ELISA, or RIA or Multiplex assay and the first is the most sensitive out of these three. Our results indicate that upon estimation by ELISA, the adipokines show an association with risk of occurrence of breast cancer.In our meta-analysis, we investigated the correlation between adipokine levels and some traditional prognostic factors of breast cancer such as menopausal status, nodal status, molecular subtypes and TNM stages. Our subgroup analysis suggested that adiponectin, leptin and resistin were associated with incidence of breast cancer in both pre- and postmenopausal women . In addi. those enrolling less than one hundred cases or controls. We used the pooled means and standard deviations of adipokine measures. Statistical tests also suggest publication bias. Fourth, the studies’s methodology used is a limitation, especially the study’s design. Our meta-analysis is mainly based on observational studies, and the inherent limitations of such studies may influence our findings. Case-control studies are mainly subject to selection bias. Besides, the prospective cohorts were over-represented in the Non-Asian group. Lastly, we only included English and Chinese language studies.It is important to mention here that this is the first meta-analysis investigating the association between various adipokines and risk of breast cancer. However, many limitations of our study need to be considered. First, significant heterogeneity existed among studies, thus results should be interpreted cautiously. Subgroup analysis indicated that detection methods and menopausal status were a potential source of heterogeneity. Age, race and the number of cases and controls in the included studies were the other possible sources of heterogeneity. Second, potential confounders might be present in observational studies, and are the intrinsic limitations of observational study design. Although some included studies had used a matching method to select the control group, the actual adipokine levels might have differed from the detection value because of the defects of detection. Third, this meta-analysis includes some studies with small sample sizes i.eA comprehensive literature search was carried out using PubMed, EMBASE and Chinese Biomedical Literature (CBM) databases using the following search criteria, “adipokines”, “leptin”, “adiponectin”, “resistin”, “interleukin 6” or “IL-6”, “Tumor Necrosis Factor alpha” or “TNF-α”, “Hepatocyte Growth Factor” or “HGF”, “Plasminogen Activator Inhibitor 1” or “PAI-1”, “visfatin”, “interleukin 8” or “IL-8”, “SFRP-5”, “lipocalin 2”, “apelin” and “breast cancer”, “obesity” or “obese” published before Sept. 15, 2015. In addition, the reference lists of these publications were manually searched for relevant articles.The eligibility of the identified articles was reviewed independently by two authors (Y.G. and L.C.). The criteria for selection of the eligible articles were as follows: (1) cross-sectional study, or case-control study (retrospective or nested case-control), or cohort study (retrospective or prospective cohort study); (2) studies investigating the adipokine levels between obese and nonobese healthy subjects; (3) studies investigating the association between adipokine level, menopausal status, detection method, study sample, or race with risk of breast cancer.et al., were included [Studies investigating tissue adipokines among male patients were excluded. In the case of multiple publications reporting the same or overlapping data, only the most recent study, or the study using the largest population, as recommended by Wu included . Studiesincluded . The autTwo authors (Y.G. and L.C.) independently evaluated the quality of the selected literature using the Newcastle-Ottawa Scale (NOS) criteria . A “scori.e. type and detection method of adipokines measurement, and study sample type), and adipokine levels (means and SDs for each group). Next, for the studies providing only the medians and ranges, we calculated the means and SDs [et al. [http://digitizer.sourceforge.net). This can read exact values by digitizing data points from an image file after manually setting the coordinate axis. Disagreements were resolved by discussion with the third reviewer (X.L.).First, we extracted the publication information , characteristics of participants , and outcome information , study results were obtained using random effects model analysis. Heterogeneity was identified by visual inspection of the forest plots, by using a standard 2-test and a significance level of +0.1, in view of the low power of such tests. Conversely, the pooled SMD were estimated using the fixed effects model analysis. Subgroup analyses were conducted to explore potential sources of heterogeneity including the detection method, sample types, and, menopausal status of patients in the included studies. Publication bias was evaluated using funnel plot analysis. The statistical analysis was performed using Review Manager 5.3 software  and a P value of less than 0.05 was considered to be significant.The summary statistic of this meta-analysis was calculated by use of the standardized mean difference ( SMD ) and the corresponding 95% CIs. Heterogeneity between articles was assessed by chi-square statistics and expressed as an “In conclusion, obese subjects had lower levels of adiponectin and higher levels of leptin and TNF-αthan non-obese subjects. Also, breast cancer patients had lower concentrations of adiponectin and higher concentrations of leptin, IL-6, IL-8, TNF-α, resistin and visfatin than controls. The patterns of altered levels of adipokine among obese subjects may be considered as specific predictors for risk of breast cancer. The results also show that changes in adipokine levels are significantly associated with increased risk of breast cancer, especially among Asians. Our results suggest the existence of an association of obesity, adipokines and risk of breast cancer in Asian women.


A novel line of research suggests that eating at nighttime may have several metabolic consequences that are highly relevant to breast cancer. We investigated the association between nighttime eating habits after 10 p.m. and breast cancer in Hong Kong women.A hospital-based case-control study was conducted during 2012–2015. A total of 922 patients with incident breast cancer (cases) and 913 hospital controls were recruited and interviewed using a standard questionnaire including information on eating behavior during both daytime and nighttime. We collected the timing, duration, types and frequencies of food intake of eating at nighttime. Odds ratios (ORs) for the risk of breast cancer in relation to nighttime eating-related variables were calculated by unconditional multivariable logistic regression.P = 0.02), and the associations were stronger in women who had the longest duration of nighttime eating (≥20 years)  and who ate late (midnight to 2 a.m.) . Interestingly, nighttime eating was only associated with breast cancer among women who consumed staple foods  but not those who ate vegetables or fruits as nighttime meals. The significant association between nighttime eating and breast cancer was observed among women with body mass index (BMI) <25  but not among women with BMI ≥25.Eating at night after 10 pm was significantly associated with breast cancer with an adjusted OR of 1.50  1.06–2.12, Results from this study suggest a possible association between nighttime eating behavior and breast cancer. These findings need to be confirmed by independent large studies.The online version of this article (doi:10.1186/s13058-017-0821-x) contains supplementary material, which is available to authorized users. Breast cancer is the most common cancer among women worldwide including women in Hong Kong , 2. AlthNight-eating behavior has become more common in recent years . EvidencNighttime eating characterized by a circadian delay in daily food intake has been associated with alterations in neuroendocrine functions, including food regulatory proteins such as leptin, ghrelin and insulin, and circadian melatonin and cortisol hormones –9. Food Data on the link between night-eating behavior and breast cancer risk are sparse, other than a few experimental studies. Results from the USA study, the National Health and Nutrition Examination Survey (NHANES) showed that an increase in nighttime fasting duration was associated with improved glycemic regulation, which may relate to a reduced risk of breast cancer . The goaDetails of the study population have been previously described , 16. BriThe inclusion criteria for control participants were: (1) Chinese women aged 20–84 years old; (2) no history of cancer; (3) admission to the same hospital during the same time period as the case participants; (4) frequency-matched by age  to case participants; and (5) residents of Hong Kong for at least 5 years. Controls were excluded if they had physician-diagnosed cancer at any site. For our controls we selected patients who had a broad spectrum of diagnoses  that were unrelated to breast cancer, to reduce or cap any possible bias , 18. TheQiGong or others), frequency and duration of each physical activity were recorded. In addition, information on commute including transportation methods and total time spent were also recorded in our questionnaire. Shift work was recorded and defined as “ever worked rotating shifts or night shift (from midnight to 5 a.m.) more than once a month for more than 1 year”. We also collected detailed data on nightshift work including type of shiftwork, frequency, duration, cumulative night shifts, and rotating schedules. Sleeping habits, including sleeping duration and quality in the last 5 years, were also collected in the questionnaire.Face-to-face interviews were conducted with both case participants and controls, by trained interviewers using a standardized questionnaire. In addition to diet, other major variables included sociodemographic characteristics, smoking and alcohol drinking, reproductive factors, family cancer history, physical activity, sleeping habits and occupational history including shift work. Anthropometric risk factors were also recorded; height and weight were self-reported, whereas waist, hip circumference and subcutaneous fat thickness were measured by our interviewers using standard measurement tools. Details of recreational physical activities, including type  of National Cancer Institute (NCI) with a slight modification . If the As nighttime food intake was not included in the NCI questionnaire, we developed specific questions to collect data on nighttime eating behavior. In order to avoid “double count”, we collected details of the type of food, timing of eating and duration of nighttime eating, instead of food frequency, which was already collected in the FFQ. Information was collected on nighttime eating and working history. For those who reported to have worked in one or more full-time jobs, a complete work history was recorded including night work/shift work status and nighttime eating behavior. Nighttime eating was defined as habitual food intake after 10 p.m. at least one time per week for more than one year. Among women who reported a history of nighttime eating, only 15% ate at nighttime less than once a week. Similar results were observed in the sensitivity analysis removing these women and therefore we used nighttime eating once or more per week as the cutoff point. Type of food, timing of eating  and duration (years) were recorded for those who reported having habitual nighttime eating. Meanwhile, for those who have never had a full-time job, nighttime eating habits within the most recent 5-year period and details of the frequency of nighttime eating and the food consumed were recorded. Detailed exposure assessment questions about nighttime eating can be found in Additional file Nighttime food intake was classified into two categories, staple foods and snacks, by meal size and type of food. Staple foods referred to a regular meal, which often contained one type of food that was rich in carbohydrate , in addition to variable vegetable or meat content; snacks referred to a portion of food smaller than a regular meal, often containing one or more items such as nuts, dairy products, bakery food, desserts or chips. Those who reported eating multiple food items including both staple foods and snacks were categorized as staple-food eaters. Within each category, food items were further classified into several different categories: noodles , rice (steamed rice and congee), baked goods , vegetables (as the main ingredient), and meat (as a primary ingredient).t test and chi-square test were performed to test the differences between case participants and controls in sociodemographic factors for continuous and categorical data, respectively. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CIs) for the association between variables related to nighttime eating and breast cancer risk, with adjustment for potential confounding factors. To select potential confounders to be included in the multivariable model, we first conducted univariate analysis with adjustment for age (age at diagnosis in case participants and age at interview in controls) and a single risk factor only.The independent P values <0.05 were further included in the final multivariable logistic regression models. The factors assessed included sociodemographic characteristics, reproductive factors, family history of cancer, history of benign breast disease and other medical conditions, smoking and alcohol consumption, anthropometric factors, physical activity, lifetime work history and shift work status, sleep pattern and exposure to light at night.All known or suspected breast cancer risk factors ascertained, including detailed shift work, were analyzed in the univariate analysis, and those with P < 0.05 in the univariate analysis; and (3) model (1) plus total dietary intake variables that were significantly associated with breast cancer. To evaluate the potential effect modification, we formally tested the interactions between nighttime eating and menopausal status, estrogen receptor (ER) status and body mass index (BMI) by including interaction terms in the regression models involving all subjects. We also conducted stratified analyses of these variables.Three multivariable regression models were presented separately, adjusted for: (1) age only; (2) age and all breast cancer risk factors with We performed a number of sensitivity analyses including analysis (1) excluding controls with digestive system disease (which may be associated with dietary intake or nighttime eating) to probe the potential bias caused by medical diseases in hospital-based controls; (2) analyzing a specific group of patients who underwent breast biopsy and were initially considered as patients with breast cancer but were eventually confirmed to be non-cancer case participants; and (3) removing women who reported particular frequencies of nighttime eating to find an appropriate cutoff point for nighttime eating behavior.The basic characteristics of case participants with breast cancer and the distribution of selected breast cancer risk factors are presented in Table P = 0.02) and dairy products . The intake of other food items did not differ significantly in case participants and controls . The association was stronger among women who consumed staple foods , particularly noodles  or rice . Breast cancer in case participants may be associated with consumption of meat at night time , but this was not statistically significant. There was no evidence of a relationship between breast cancer and the consumption of vegetables  or fruits  at nighttime.Associations between nighttime eating habits and breast cancer are summarized in Table P = 0.02). The association with nighttime eating did not seem to vary significantly by the timing of food consumption, although eating between midnight and 2 a.m. had the strongest effect in the multivariable model .We further conducted a more detailed analysis of the 894 case participants and 882 control participants who had completed records on duration and timing of nighttime eating habits Table . Long duResults of analyses stratified by menopausal status and ER status are presented in Additional files P < 0.001) but not among women with BMI ≥25 . A similar pattern was observed in subgroup analyses by meal and food type (Table P for interaction = 0.01 particularly for consumption of staple food (P for interaction = 0.03). Similar results were obtained when a different cutoff (BMI = 23) was used (data not shown).Table pe Table . The intSimilar results were obtained from the sensitivity analysis excluding controls with digestive disease (data not shown). Furthermore, to evaluate the influence of recall or interview bias, we compared the proportion of patients who reported nighttime eating among a group of 131 patients, who were initially suspected of having breast cancer but eventually were confirmed to have benign breast disease, to all controls and observed similar frequencies of nighttime eating .In this breast cancer case-control study among Chinese women in Hong Kong, we showed that nighttime eating might be significantly associated with risk of breast cancer, in particular among women with BMI <25, who have had nighttime eating habits for more than 20 years and who consume energy-dense foods rich in carbohydrate after 10 p.m. (such as rice or noodles), implicating nighttime eating as a potential new risk factor for breast cancer.Nighttime eating has long been reported to have a negative impact on health and body composition, with consequences that include weight gain and obesity, which are well-known risk factors for postmenopausal breast cancer . Animal The mechanisms underlying the association between nighttime eating and risk of breast cancer remains unknown and may be mediated through weight gain and obesity , 21–24, Consistent with a recent large meta-analysis  and two This study provides new insights into nighttime eating habits as potential risk factors for breast cancer. However, we are aware that our study is limited by the hospital case-control design and the small number of subjects, and therefore our findings need to be interpreted with caution. Large prospective studies are needed to confirm these results. Nevertheless, we conducted detailed analyses of nighttime eating variables such as timing, duration, frequency, and type of food consumption, with careful adjustment for known breast cancer risk factors, total dietary habits and night shift work.We also conducted several sensitivity analyses to assess whether the associations were influenced by recall bias or the potential issue related to self-reported dietary habits among hospital controls. In order to minimize recall bias, we recruited only case participants with incident cancer and tried to introduce this study to participants as a general “women’s health” study rather than a cancer study. Analysis of test-re-test reliability was also conducted to check the reproducibility of interview results. Telephone interviews were conducted by the same interviewer at least one month after the first interview with 158 case participants (17.1%) and 153 controls (16.8%). There was good agreement for identification of nighttime eating exposure  between the first and second interviews. In addition, in sensitivity analysis comparing 131 patients, who were initially suspected of having breast cancer but eventually were confirmed to have benign breast disease, to all controls also suggested that recall or interviewer bias may not have seriously influenced our results. Further, dietary habits in hospital controls may differ from those of the general population due to health conditions, consciousness or diseases, particularly among those with diseases of the digestive system. However, previous methodology studies showed that even if a particular segment of the controls has altered diet practices, bias is constrained . In suppDue to the retrospective study design, data on quantities of food intake or total calorie intake were not collected due to difficulty in accurately recalling the amounts of food consumed a long time ago. To address this limitation, we accounted for the overall consumption of different types of food items and BMI in our analyses. Further, we found that the association between nighttime eating and breast cancer was more significant among slim women, suggesting that the association was not driven by excessive calories.The FFQ is a tool to estimate food and nutrient consumption and has been widely used in investigating the associations between diet and chronic disease . HoweverIn conclusion, our findings suggest that nighttime eating was more common among breast cancer case participants compared with control participants. More epidemiological studies, especially with a prospective design and a large number of subjects, are needed to confirm this association and to explore the underlying mechanisms.


Breast cancer treatment, including radical surgery, is also pursued as late as the 7th - 8th decade of women’s lives. Standard physical rehabilitation procedures offered to those women are predominantly focused on attenuating specific functional deficits of the upper limb and trunk. Seldom do they entail any regimens specifically aimed at recovering overall functionality, and reducing exposure to falls-risk.The study aimed to assess potential interrelationships between the self-reported falls, individual functional capabilities and appreciably reducing exposure to falls-risk in a group of post-menopausal, post-surgical breast cancer survivors.The study recruited 102 women , post-surgical breast cancer survivors. The subjects were stratified by age into three groups: Group 1 (65–69 years); Group 2 (70–74 years), and Group 3 (75–79 years). Individual functional capabilities were assessed with Eight-foot up & go test (8UG), chair stand test (CST), and 2-minute step test (2ST). Tinetti POMA test was applied to assess gait and balance disorders. Self-reported falls in the past year were ascertained through a questionnaire.Assessment of individual aerobic endurance (2ST) also demonstrated a clear deficit in the mean scores category in all respective age sub-groups, as compared against the reference values. The deficits ranged from 4.86 to 15.90 steps less than the normative values; the oldest subjects demonstrating the largest deficit. The aerobic endurance tests results significantly impacted the ultimate assessment of an individual falls-risk in the oldest group. The analysis of the number of falls sustained within the recent year indicated that 43.67% of the subjects fell victim of such incidents.An individual exposure to falls-risk was found to be appreciably more dependent upon individual aerobic endurance rather than overall strength of the lower part of the body in the breast cancer survivors over 75. A sustained rise in the incidence of breast cancer has sparked off some concerns that during comprehensive therapeutic management, including radical surgical intervention, there is an appreciable reduction in physical activity and functional capabilities in the older women.Effective breast cancer treatment and attendant surgical interventions are sometimes pursued as late as the 7th - 8th decade of their lives. Most of them boast an appreciable success rate, consequently facilitating complete recovery and thus allowing senior women to get on with their lives despite having gone through such a traumatic experience.Physical rehabilitation procedures offered to these senior post-surgical breast cancer survivors are generally focused on attenuating the limb edema on the operated side, improving overall range of motion and muscle strength within the limb, and alleviating any residual dysfunctions around the trunk area . Very seFurthermore,. approx. 50% of working age women under treatment for breast cancer are not involved in any form of intense physical activity (defined as > 6MET-h per week), whereas for 25% of them this activity accounts for less than 3 MET-h, which is equivalent to walking at the speed of 4.8 km/h [It should also be noted that a steadily increasing proportion of women diagnosed with breast cancer is expected to be at an advanced age ,5. We caAdvanced age compounded by the side effects originating from a complex therapeutic management of cancer makes the initiation and uptake of remedial measures to maintain function more difficult, but of crucial importance in secondary preventive care, with a view to maintaining individual self-reliance and quality of life.Female gender is deemed a legitimate risk factor for balance disorders and accidental falls also by Francis and Rubenstein ,7. WomenThere is precious little to be found in the literature on falls, falls-risk, functional capability, or balance in the older women undergoing breast cancer treatment. As falls pose a huge threat to individual self-reliance, quality of life and psychological wellbeing, it is essential to ascertain whether falls are common in women undergoing breast cancer treatment, and which specific functional capabilities may actually need improvement through intervention to reduce their exposure to falls-risk ,10.The present study aims to provide some brand-new insights into the functional capabilities  of senior breast cancer survivors and their exposure to falls-risk, while in view of its application character may also offer some hands-on guidance to the rehabilitation teams working with this group of patients, with a view to giving due consideration to the specific rehab procedures aimed specifically at enhancing overall functional capabilities , while designing and structuring any individually tailored rehab regimens.The study group was comprised of women over 65 years of age, having undergone a surgical intervention for breast cancer in the Cancer Centre. The subjects had sustained a radical mastectomy on one side of the chest, without the benefit of a reconstructive surgery. Written invitations to take part in the survey had been sent out to all the women. Out of 466 post-surgery women 48 died , 8 women did not consent to participating in the study , and 237 failed to respond to the invitations.The study recruited 102  women aged 65–79  undergoing breast cancer treatment at the Cancer Centre. The subjects were divided up into the three age groups: Group 1 ; Group 2 , and Group 3 .The gait and balance disorders were assessed with the Tinetti POMA test . The datGait speed was ascertained on a 6-metre distance, in line with the formula: gait speed = distance covered: time taken to cover the set distance.Their balance agility and gait were assessed using the Eight-foot up & go (8UG) test , a 2-minute step test (2ST) (assessment of aerobic endurance), and a chair stand test (CST) (assessment of the strength of the lower part of the body), i.e. three of the component tests in the Senior Fitness Test battery .All study protocol procedures were duly approved by the Bioethics Review Committee, District Chamber of Physicians (No 19/KBL/OIL/2011).All examination results were analyzed using Med. Calc 12.1.0. and p≤0.05 were considered statistically significant. The following methods were applied in the statistical analyses: The Kolmogorov-Smirnov compatibility test for the assessment of normal distribution of the tested variables. Basic statistics  to provide a general characteristics of the study subjects. The Kruskal-Wallis one-way analysis of variance by the ranks test for the comparison of variations of parameters in the studied group of subjects under the influence of independent variables of abnormal distribution, along with a post hoc Conover test for multiple comparisons of the mean values of the assessed parameters. The Mann-Whitney test for the comparison of the mean values of the assessed parameters, as well as the differences between the respective parameters within the group of subjects under study. The assessment of the mean trends and of the diffusion, with a view to comparing the values of the assessed parameters with the reference values. The correlation analysis for assessing the significance of the correlation between the respective parametric variables. In order to assess the incidence of falls within the recent year, as well as the final scores of the Tinetti POMA test , the actual number of such occurrences within the study population was calculated.Assessment of individual agility and dynamic balance when walking, as facilitated by the “Eight-foot up & go” test scores, demonstrated that the study subjects exceeded the set reference values for all respective age categories .Assessment of the strength of the lower part of the body (“Chair stand test” scores) demonstrated a clear deficit in the mean scores category in all respective age sub-groups of women, as compared against the reference values. The deficits ranged from 0.32 to 1.24 chair rises less than the normative values would suggest, and the oldest appeared to have the largest deficit.The assessment of individual aerobic endurance (“2-minute step test” scores) also demonstrated a clear deficit in the mean scores category in all respective age sub-groups of women, as compared against the reference values. The deficits ranged from 4.86 to 15.90 steps less than the normative values would suggest, and the oldest appeared to have the largest deficit.post hoc test scores revealed a statistically significant difference between the respective sub-group subjects  (p<0.05)  .There was a statistically significant age effect on the gait speed in all respective age sub-groups of women (p<0.05) .Based on the review of the final Tinetti POMA test results, conducted in all respective age sub-groups, the study population was subsequently divided into the lower and higher risk groups in terms of respective propensity for accidental falls. Nearly 10% of the over 70 study subjects were classified as remaining at high falls-risk .The analysis of the number of falls sustained within the recent year indicated that 43.67% of the subjects fell victim of such an experience.There was a statistically significant relationship between gait speed and a risk of fall (p<0.05). In all respective age sub-groups a higher gait speed was found to significantly diminish that risk .In two out of three groups under study, the test scores (Tinetti POMA test) pertaining to the strength of the lower part of the body significantly impacted an individual risk of fall .The results yielded by the aerobic endurance tests significantly impacted the ultimate assessment of an individual falls-risk in the oldest group only .Statistically significant differences were noted in the gait speed between the women who had been categorized  as at high risk (0–18) and low risk (19–28), respectively. The lower falls-risk sub-group (Median 0.61 m/s), and the higher risk sub-group (Median 0.29 m/s) were significantly different (p<0.001).Significant differences in the strength of the lower part of the body between the women who had been allocated to the lower falls-risk sub-group and the ones from the higher risk sub-group were observed (p<0.05).Individual functional capability is widely acknowledged to be of vital importance for older people in terms of coping effectively with the daily tasks and everyday challenges posed by a diversity of environmental factors . Older people are routinely faced with numerous obstacles that act as the specific barriers for participation in everyday activities, including the lack of, or incorrect information provided by the health care professionals. Adequate and appropriate encouragement offered to a patient upon discharge from hospital is pivotal for the effective uptake of a physical rehabilitation program .In the older women, following breast cancer treatment, there is a deficit of endurance and lower body strength (compared to published normative data for the same age groups) and a higher falls-risk in those with poor balance. As seen in healthy older women, there is a decline in functional capabilities with increasing age, unlikely to be resultant from treatment ,14.Numerous authors emphasize that breast cancer treatment results in a diversity of side effects, which may hinder physical activity and reduce the uptake of exercise interventions ,16,17. ILimited physical capability is particularly apparent in decreased maximum oxygen consumption rate (VO2max), and in other symptoms referenced in the functional examinations, or questionnaires comparing physical activity of the subjects before and after the implementation of the actual treatment management ,19.Among the other reported causes of diminished physical performance are pain, edema, restricted body movement and muscular weakness which lead to diminished overall physical activity and a lifestyle virtually devoid of significant physical effort .Diminished physical performance manifested itself as an appreciably faster sub-maximal heart rate, as well as by twice the rate of oxygen consumption at the same energy equivalent. Fatigue appears faster, consequently causing the body’s center of gravity to sway sideways more, reaction time increases, muscle strength in the lower extremities diminishes, and all those factors combined stand for an increased falls-risk.Interestingly, no differences in the level of physical performance were dependent on the breast cancer treatment method  suggesting that restricted physical activity and movement were the main contributing factors .In view of the above, it seems both prudent and justifiable to introduce a range of tests aimed at assessing individual functional capabilities in the women treated for breast cancer, initially prior to a radical surgical intervention, and then within certain intervals following its completion (e.g. every few months), simultaneously putting the subjects on an individually tailored rehabilitation exercise regimen expected to be of overall advantage to them.In the present study we also assessed an individual’s propensity for falls using the Tinetti POMA test and a self-report comprised within a falls questionnaire. The results revealed that 10% (9.7%) of women under breast cancer treatment happened to be in the high risk of fall group. Indeed, 43.67% of the subjects reported a single, or recurrent falls sustained within the recent year. The number of falls increased with age. In the women following breast cancer treatment, a fall constitutes a significant health hazard, not only due to the risk of fracture, but also to a diversity of potential complications that might originate in the upper limb on its operated side, e.g. edema.In the breast cancer survivors (BCSs) the risk of bone fracture is significantly higher (despite no bone metastases) than in the non-BCSs within the same age group. Radiotherapy effectively changes the bone density and consequently its micro-architecture . The redWinters-Stone et al. also assessed the women (n = 59) undergoing breast cancer treatment, with a view to establishing their propensity for falls. The subjects were queried about the number of accidental falls actually sustained within the recent year. The findings implied that the recently treated postmenopausal BCSs sustained a higher number of falls, as compared to the population averages for the community-dwelling elderly adults. The authors reported that 58% of the BCSs had sustained a fall within the year preceding the actual enrolment into the study, whereas nearly half of them (47%) fell victim of such an experience within 6 months of its commencement .The findings further implied that the balance-related problems may have been related to the specific changes in the vestibular system, associated with the chemotherapy treatment .The findings of the above referenced study correlate with the results obtained by Chen et al., where the BCSs were exposed to a 15% higher falls-risk than the non-BCSs .Significant changes in posture stability were also observed by Wampler et al. in the study embracing 22 women undergoing taxane chemotherapy, as compared to the non-BSCs control group. The authors noted that the BSCs treated with the taxane-based chemotherapy had worse visual acuity at the low, although not at the high contrast, as compared to the controls .The studies of Winters-Stone, as well as those by Wampler, imply that breast cancer treatment may adversely affect the vestibular impulse to the balance control, which consequently may precipitate accidental falls in the subjects ,25.Similar symptoms are reported by the patients undergoing chemotherapy treatment. Based on the study of the BCSs still undergoing chemotherapy, and those who had this treatment already completed, Huang et al. concluded that those subjects experienced greater balance problems, as compared to the reference values .The findings of the present study highlight the statistically significant correlations between gait speed , strength of the lower part of the body (Groups 1 and 2), individual aerobic endurance (Group 3), and the results of the Tinetti POMA test which indicate appreciably better individual functional capability results in the higher scores in the Tinetti POMA test. The women subjects allocated to the lower risk group scored better in the gait speed, and the strength of the lower part of the body, as compared to those allocated to the high risk group.There was a small percentage of women in the 'high falls-risk' category, as established with the aid of the Tinetti/POMA test, yet a much higher number/proportion of women who actually reported sustaining falls. Lower scores in the 2-minute step test might well be related to balance disorder encountered in post-mastectomy women.Cancer disease and its therapeutic management leads to an appreciably diminished individual physical capacity, reduced functional capabilities, and a propensity to fall in these patients . These effects are additive to the effects of age on functional capacities .ThereforKey falls-risk factors, as commonly acknowledged throughout the literature on the subject, indicate that it is in fact the muscle weakness that is being deemed a clearly predictive variable for accidental falls in the seniors over 75. More than a quarter of the study subjects had undergone radio- and chemotherapy. Consequently, if radiotherapy should weaken cancellous (spongy) bone structure, thus negatively affecting overall physical activity, then reduced visual acuity caused by chemotherapy may well cause all physical activity to be shunned by a patient. This tendency is particularly manifest when physical activity of women subjects succumbs to linear regression with advancing age, i.e. as of the actual date of an adverse diagnosis, as attested to by a 2-fold decrease in the baseline values within a decade.In the women breast cancer survivors over 75, however, exposure to falls-risk has been found to be far more dependent upon individual aerobic endurance than overall strength of the lower part of the body. Consequently, the principal focus in designing specific rehab regimens for this group of patients should rest firmly on boosting individual aerobic endurance, with the muscle strength being an issue of secondary therapeutic importance.Walking speed changed with the patients’ age and incrementally diminished by as much as ca. 30% every 10 years. As such observations actually highlighted this as a complex rehabilitation issue, all attending physiotherapists should feel well motivated to have their therapeutic regimens, as offered to this particular age group, tailored accordingly, in due consideration of the present study findings.


Genetic risk assessment for breast cancer and ovarian cancer (BCOC) is expected to make major inroads into mainstream clinical practice. It is important to evaluate the potential impact on women ahead of its implementation in order to maximise health benefits, as predictive genetic testing without adequate support could lead to adverse psychological and behavioural responses to risk disclosure.To examine anticipated health behaviour changes and perceived control to disclosure of genetic risk for BCOC and establish demographic and person-specific correlates of adverse anticipated responses in a population-based sample of women.Cross-sectional quantitative survey study carried out by the UK Office for National Statistics in January and March 2014.Face-to-face computer-assisted interviews conducted by trained researchers in participants’ homes.837 women randomly chosen from households across the UK identified from the Royal Mail’s Postcode Address File.Anticipated health behaviour change and perceived control to disclosure of BCOC risk.In response to a genetic test result, most women (72%) indicated ‘I would try harder to have a healthy lifestyle’, and over half (55%) felt ‘it would give me more control over my life’. These associations were independent of demographic factors or perceived risk of BCOC in Bonferroni-corrected multivariate analyses. However, a minority of women (14%) felt ‘it isn’t worth making lifestyle changes’ and that ‘I would feel less free to make choices in my life’ (16%) in response to BCOC risk disclosure. The former belief was more likely to be held by women who were educated below university degree level (P<0.001) after adjusting for other demographic and person-specific correlates.These findings indicate that women in the UK largely anticipate that they would engage in positive health behaviour changes in response to BCOC risk disclosure. Stratified random sampling, the ‘gold-standard’ for survey recruitment, was used in this study.The study reports on anticipated responses to genetic breast cancer and ovarian cancer (BCOC) risk information from a large general population sample of women living in the UK.The survey questions were broad and may have been interpreted differently by different participants.A general hypothetical scenario about receiving genetic BCOC risk information was used instead of asking participants to consider a hypothetical scenario of receiving a high-risk or low-risk genetic test result.BRCA1 and BRCA2, which confer a very high lifetime risk of BCOC ,BRCA1 and BRCA2 confer a lifetime risk for cancer of 50% or greater, the lifetime risk for moderately penetrant genes ranges from 20% to 50%, and low penetrance genes are thought to have a limited effect.Advances in genetic technologies have led to the identification of gene mutations associated with an increased risk of developing breast cancer and ovarian cancer (BCOC). In addition to germline mutations in BRCA1 and BRCA2 is conducted in clinical practice only, in individuals with a strong family history or after a cancer diagnosis. However, it has been argued that this approach is likely to miss a substantial proportion of women at high risk (~30%), particularly if the family is small, the mutation was transmitted through the paternal line or the individual has a number of lower-risk variants whose effects are additive.http://www.mcgprogramme.com/).BRCA1 and BRCA2 testing may be offered to women diagnosed with triple negative breast cancer, and information on genetic status is likely to influence clinical care and management of the patient and the family.www.23andme.com; www.getcolor.com). The notion that individuals have a ‘right to know’ their genetic information has also gained traction in recent years.To date, genetic testing of However, concerns persist about patient safety related to poor psychological adjustment following genetic risk disclosure. Studies investigating reactions to disclosure of BRCA status commonly do not find evidence for persistent negative psychological outcomes beyond 1 year after result disclosure.Currently, one-to-one genetic counselling is strongly embedded within clinical genetic testing services, offering education and support throughout the process. If genetic testing were introduced on a population level, the current model of delivering genetic counselling would no longer be feasible. It has been argued that returning genetic risk test results for highly debilitating conditions such as BCOC without appropriate professional guidance would leave room for misinterpretation and uncertainty, increasing the risk of adverse psychological outcomes.Although a wealth of studies have investigated anticipated psychological reactions to disclosure of BCOC genetic risk in higher-risk groups,An early population-based survey investigated attitudes towards genetic testing for breast cancer among 836 women living in Washington State.The aim of the present study was to examine the anticipated health behaviour changes and perceived control in response to disclosure of genetic risk for BCOC and to explore demographic and person-specific correlates  of anticipated response among a population sample of women in the UK. Identifying subgroups who are more likely to anticipate a negative response to learning about their genetic risk of developing these cancers, before genetic testing is integrated into mainstream healthcare , gives scope for timely intervention to avoid further increasing disparities in healthcare.http://ethics.grad.ucl.ac.uk/exemptions.php).This quantitative study complied with the principles set out in the Declaration of Helsinki. As a population-based anonymous survey, it was exempt from ethical approval, in accordance with the guidelines set out by the University College London ethics committee for non-National Health Service research  in their monthly survey which is conducted on behalf of a range of organisations . Each month, 2010 households are identified from the Royal Mail’s Postcode Address File using stratified random probability sampling. Selected addresses are contacted up to eight times at different times and days of the week to maximise response rates. One person aged over 16 years from each household is randomly chosen to complete a computer-assisted face-to-face interview with trained researchers. Surveys commonly include a variety of different topics, making participation bias unlikely, although participants can opt out at any point. Questions on the ‘genetics and screening’ module were included in data collection waves in January and March 2014.The ‘genes and cancer’ module was introduced with a short statement: ‘Genes contain the ‘instruction manual’ of life, called DNA. Genes are passed from parents to their children. Nowadays, it is possible to predict whether someone is likely to develop certain diseases by looking at their genes. This is called genetic testing’. No further information was given, as we were interested in women’s attitudes towards BCOC genetic testing based on their current understanding of it. Participants were asked several questions in relation to genetic testing for BCOC risk and attitudes on breast cancer screening  or to pursue health behaviours aimed at mitigating risk , to more negatively framed outcomes such as curtailing freedom of choice  or the perceived futility of attempting behaviour change . All items were scored on a 5-point Likert scale ranging from ‘strongly disagree’ to ‘strongly agree’ and were adapted from previous research.Perceived risk of BCOC was each assessed with one question ‘Compared with other women of your age, what do you think are your chances of getting breast [ovarian] cancer’ with response options of: ‘much lower than others’, ‘lower than others’, ‘the same as others’, ‘higher than others’ and ‘much higher than others’. Given that individual risk categories pertaining to much lower/much higher perceived risk were small, perceived risk was grouped into three categories: ‘much lower/lower than others, ‘same as others’ and ‘higher/much higher than others’.https://tinyurl.com/ya6gn2g6). Age was coded as ≤50 years vs >50 years to investigate any generational differences in anticipated reactions and attitudes. We chose 50 years as the cut-off point since public interest in the UK for genetic testing has been reported as being greatest for people aged 46–60 years,Age, ethnicity, educational attainment and marital status were derived using standard survey items . Descriptive statistics were explored using frequency tables. We explored demographic  and person-specific predictors  for each outcome variable using χhttp://www.ons.gov.uk/ons/index.html). The total female sample was n=1095.Data for the current study were collected in two waves: January and March 2014. In the January wave, 8% (n=166) of the 2010 selected households were not eligible because they were businesses or empty properties. Of 1844 eligible households, 9% (n=171) could not be contacted, and 33% (n=608) declined to take part in the ONS survey. In the March wave, 1853 households were eligible (92%). Of those, 13% (n=237) could not be contacted, and 31% (n=578) chose not to take part. Therefore, the overall response rate was 57%, comparable to previous ONS surveys .After excluding participants with incomplete data for any of the outcome variables (n=120) or who were aged younger than 18 years or older than 74 years (n=138), the final sample for analysis consisted of 837 women. Although 36.4% (n=305) of the sample reported a family history of any cancer, most women felt that they were not particularly at risk of breast or ovarian cancer; only 9.9% (n=83) thought that they were at ‘higher’ or ‘much higher’ than average risk of breast cancer, and even fewer  thought that they were at ‘higher’ or ‘much higher’ risk of ovarian cancer. A full breakdown of responses can be found in the online Overall, women were supportive of the idea of genetic testing for breast and ovarian cancer. Only 2.0% (n=18) thought that it was ‘never’ a good time to have a genetic test. However, about a third of the sample  were ‘unsure’. Opinions were divided on when the best time would be to get tested, with 8.3% (n=77) thinking that it would be ‘just after birth’, just over a quarter  thought ‘during school’, 10.6% (n=98) reported ‘just before marriage’, 16.9% (n=156) said ‘before they plan to have a child’ and 3.4% (n=31) thought the best time would be ‘when they are unwell’. There were no demographic or personal correlates with ‘ever’ versus ‘never’ supporting genetic testing for breast and ovarian cancer (data not shown).Overall, women anticipated to respond proactively to awareness of their genetic risk. Most  said that they ‘would try harder to have a healthy lifestyle’, and over half  anticipated that it would give them ‘more control over my life’. However, a minority reported that it would ‘not be worth making lifestyle changes’  in response to genetic risk disclosure and that they would feel ‘less free to make choices in my life’ .2 (1)=4.57, P=0.032), were married (χ2 (1)=4.53, P=0.033) or had a family history of cancer (χ2 (1)=5.51, P=0.019) were significantly more likely to report that awareness of genetic risk would give them more control over their life =7.17, P=0.007), and this association remained in multivariate analyses . Women from ethnic minority backgrounds (χ2 (1)=4.18, P=0.041), those who perceived themselves at a (much) lower or (much) higher risk of breast cancer (χ2 (4)=11.08, P=0.026) or ovarian cancer (χ2 (4)=22.38, P<0.001) were more likely to report that awareness of genetic risk would make them ‘feel less free to make choices in their life’, but none of these findings were maintained after adjusting for demographic and person-specific factors and for multiple testing However, the finding that women with fewer years of formal education are less likely to believe that lifestyle changes could be effective for cancer prevention also echoes studies that investigated attitudes towards cancer screening. These studies have found that women with lower socioeconomic status, which is linked to educational attainment and information literacy,Although previous studies in both higher-riskWe found no association between participants’ anticipated response to genetic risk disclosure and perceived risk of either breast or ovarian cancer. However, since few women considered themselves to be at ‘higher’ or ‘much higher’ than average risk of BCOC, sample sizes may have been too small to detect associations. Alternatively, these findings may suggest that UK women may have a more realistic understanding of their personal risk of BCOC compared with reports in previous studies from other countries.The strengths of this study are the approach to sampling  and the statistical adjustment for multiple testing, which gives confidence in the robustness of the findings. However, the study also had important limitations. We only assessed anticipated responses to disclosure of genetic risk of BCOC in general, not whether these differed in response to a hypothetical ‘higher’ or ‘lower’ genetic risk. Although all questions have been used in previous research with different samples, with comparable findings, anticipated lifestyle changes and their perceived effectiveness could vary depending on the levels of risk conferred. Further research could explore whether attitudes to genetic risk disclosure of BCOC differ when considering different levels of risk. Second, because of survey constraints, we focused our investigation on a limited set of broad questions which could have been interpreted differently by participants. Questions therefore remain about exactly how respondents anticipated changing their behaviour. Future research could investigate this topic with more in-depth questions.Naturally, responses to ‘real’ disclosure of genetic risk information may be less positive than our results suggest; while most participants in this study anticipated making an effort to ‘have a healthy lifestyle’, research has shown that there is generally a ‘gap’ between intentions and actual behaviour.Overall, findings from this study indicate that women in the UK are generally positive about the prospect of population-based genetic testing for risk of BCOC. However, those with fewer years in education may be less positive. Given that there are already existing disparities in uptake of available means of early detection for breast cancer, careful planning is needed to avoid increasing these further. There are concerns in professional circles that predictive genetic testing without adequate support could lead to adverse psychological and behavioural responses to risk disclosure. Although the risk of psychological harm may in part be mitigated by self-selection into genetic testing,