Dietary habits, lifestyles, and overall adherence to 2018 WCRF/AICR cancer prevention recommendations among adult women in the EPIC-Florence cohort: Changes from adulthood to older age and differences across birth cohorts.

OBJECTIVES, SETTING AND PARTICIPANTS: We aimed to examine changes in dietary habits, lifestyles (e.g., smoking, physical activity levels, and alcohol intake), anthropometry, other individual health-relevant characteristics, and overall adherence to 2018 WCRF/AICR cancer prevention recommendations, among women enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Florence cohort. DESIGN AND MEASUREMENTS: We fitted age- and energy intake-adjusted generalized linear models to describe (a) changes occurring over a person's lifetime in the transition from adulthood to older age, and (b) differences between women aged 56-60 years belonging to two birth cohorts spaced apart by around 25 years (born in 1933-1941 vs. 1958-1964). RESULTS: Dietary habits and overall adherence to cancer prevention recommendations improved among women (n = 3,309) followed from adulthood to older age (mean age 47.4 and 71.8 years, respectively), despite increases in the prevalence of adiposity and sedentary lifestyle. Women in the younger birth cohort (n = 163) showed significantly greater overall adherence to cancer prevention recommendations than in the older birth cohort (n = 355), but had more often a positive smoking history and an average larger waist circumference. CONCLUSION: A trend toward better adherence to cancer prevention recommendations emerged when analyzing adult-to-older-age trajectories and differences across birth cohort, yet some critical issues were also identified. Continuous monitoring is essential to detect changing prevention needs and adapt public health policies and practices.

Cigarette smoking and mammographic breast density in post-menopausal women from the EPIC Florence cohort.

Introduction: Cigarette smoking has been recognized as a risk factor for breast cancer (BC) also if the biological mechanism remains poorly understood. High mammographic breast density (MBD) is associated with BC risk and many BC risk factors, such as genetic, anthropometric, reproductive and lifestyle factors and age, are also able to modulate MBD. The aim of the present study was to prospectively explore, in post-menopausal women, the association between smoking habits and MBD, assessed using an automated software, considering duration and intensity of smoking. Methods: The analysis was carried out in 3,774 women enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) Florence cohort in 1993-98, participating in the 2004-06 follow up (FU) and with at least one full-field digital mammography (FFDM) performed after FU. For each woman, detailed information on smoking habits, anthropometry, lifestyle and reproductive history was collected at enrollment and at FU. Smoking information at baseline and at FU was integrated. The fully automated Volpara™ software was used to obtain total breast volume (cm3), absolute breast dense volume (DV, cm3) and volumetric percent density (VPD, %) from the first available FFDM (average 5.3 years from FU). Multivariable linear regression models were applied to evaluate the associations between smoking habits and VPD or DV. Results: An inverse association between smoking exposure and VPD emerged (Diff% -7.96%, p <0.0001 for current smokers and -3.92%, p 0.01 for former smokers, compared with non-smokers). An inverse dose-response relationship with number of cigarettes/day, years of smoking duration and lifetime smoking exposure (pack-years) and a direct association with time since smoking cessation among former smokers emerged. Similar associations, with an attenuated effect, emerged when DV was considered as the outcome variable. Discussion: This longitudinal study confirms the inverse association between active smoking, a known risk factor for BC, and MBD among post-menopausal women. The inclusion of smoking habits in the existing BC risk prediction models could be evaluated in future studies.

Lifetime changes in body fatness and breast density in postmenopausal women: the FEDRA study.

BACKGROUND: High mammographic breast density (MBD) is an established risk factor for breast cancer (BC). Body fatness conveys an increased BC risk in postmenopause but is associated with less dense breasts. Here, we studied the relationship between body fatness and breast composition within the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) longitudinal study. METHODS: Repeated anthropometric data and MBD parameters (obtained through an automated software on BC screening digital mammograms) were available for all participants, as well as information on other BC risk factors. Multivariate linear regression and functional data analysis were used to longitudinally evaluate the association of body fatness, and changes thereof over time, with dense (DV) and non-dense (NDV) breast volumes and volumetric percent density (VPD). RESULTS: A total of 5,262 women were included, with anthropometric data available at 20 and 40 years of age, at EPIC baseline (mean 49.0 years), and an average of 9.4 years thereafter. The mean number of mammograms per woman was 3.3 (SD 1.6). Body fatness (and increases thereof) at any age was positively associated with DV and NDV (the association being consistently stronger for the latter), and inversely associated with VPD. For instance, an increase by 1 kg/year between the age of 40 years and EPIC baseline was significantly associated with 1.97% higher DV, 8.85% higher NDV, and 5.82% lower VPD. CONCLUSION: Body fatness and its increase from young adulthood until midlife are inversely associated with volumetric percent density, but positively associated with dense and non-dense breast volumes in postmenopausal women.

The FEDRA Longitudinal Study: Repeated Volumetric Breast Density Measures and Breast Cancer Risk.

Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We investigated the association between volumetric MBD measures, their changes over time, and BC risk in a cohort of women participating in the FEDRA (Florence-EPIC Digital mammographic density and breast cancer Risk Assessment) study. The study was carried out among 6148 women with repeated MBD measures from full-field digital mammograms and repeated information on lifestyle habits, reproductive history, and anthropometry. The association between MBD measures (modeled as time-dependent covariates), their relative annual changes, and BC risk were evaluated by adjusted Cox models. During an average of 7.8 years of follow-up, 262 BC cases were identified. BC risk was directly associated with standard deviation increments of volumetric percent density (VPD, HR 1.37, 95%CI 1.22-1.54) and dense volume (DV, HR 1.29, 95%CI 1.18-1.41). An inverse association emerged with non-dense volume (NDV, HR 0.82, 95%CI 0.69-0.98). No significant associations emerged between annual changes in VPD, DV, NDV, and BC risk. Higher values of MBD measures, modeled as time-dependent covariates, were positively associated with increased BC risk, while an inverse association was evident for increasing NDV. No effect of annual changes in MBD emerged.

Serum heavy metals and breast cancer risk: A case-control study nested in the Florence cohort of the EPIC (European Prospective Investigation into Cancer and nutrition) study.

BACKGROUND: Chronic exposure to heavy metals is of concern for its potential carcinogenic effect. An association with increased breast cancer (BC) risk was hypothesized, but literature data are conflicting and the question remains unresolved. We aimed to investigate the association between heavy metals and BC risk in a case-control study nested within the Florence section of the EPIC (European Prospective Investigation into Cancer and nutrition) cohort. METHODS: We included 150 BC cases and an equal number of controls individually matched to cases by age and year of enrolment. In order to avoid confounding by smoking, the study was restricted to never smokers. Serum levels of six heavy metals (Cd, Co, Cr, Mn, Pb, and Tl) were quantified in pre-diagnostic samples using inductively coupled plasma mass spectrometry. Odds ratios (ORs) and corresponding 95 % confidence intervals (CI) were calculated via multivariable conditional logistic regression models. RESULTS: Serum levels of cobalt were inversely associated with BC risk (OR for the comparison of 3rd vs. 1st tertiles: 0.33, 95 % CI 0.12-0.91, p-value 0.033). None of the other heavy metals under study was significantly associated with BC risk in multivariable models. For Cd, Cr, and Tl, over half of the study participants had serum levels below the limit of quantitation. CONCLUSIONS: Our results do not support the hypothesis that exposure to heavy metals is associated with an increased BC risk among never smokers from the general population. The inverse association between cobalt serum levels and BC risk requires confirmation in future studies.

Adipocytokine plasma level changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women.

BACKGROUND: Adipocytokines are signaling molecules secreted by adipose tissue contributing to the control of body fat, energy expenditure and secretion of insulin and cytokines. They have been related to the development of obesity, type-2 diabetes, cardiovascular diseases and cancer. Diet and physical activity (PA) may have beneficial effects on their level. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of adipocytokines as a secondary analysis in the DAMA (Diet, physical Activity and Mammography) trial. METHODS: The 234 study participants (healthy postmenopausal women with high breast density, 50-69 years, non-smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Leptin, resistin and adiponectin were measured at baseline and at the end of the intervention. Analyses were performed using Tobit regression. RESULTS: After 24 months, women randomised to PA intervention (arms #2 + #3) showed significant lower level of leptin (37.5% lower) and resistin (65.6% lower) compared to the control group (arms #1 + #4). No significant differences emerged in adiponectin levels. No significant differences in leptin, resistin and adiponectin levels at follow-up emerged in women randomised to the dietary intervention (arms #1 + #3) in comparison with controls (arms #2 + #4). CONCLUSION: This study supports the effectiveness of PA, even at moderate intensity, in improving the leptin and resistin profile in postmenopausal women. TRIAL REGISTRATION NUMBER: ISRCTN28492718, date of trial registration 17/05/2012.

Dietary Patterns, Dietary Interventions, and Mammographic Breast Density: A Systematic Literature Review.

BACKGROUND: Breast cancer (BC) is the most common and deadliest malignancy among women. High mammographic breast density (MBD) is an established modifiable risk marker for BC, and it is of interest, for prevention purposes, to consider lifestyle factors that may modulate both MBD and BC risk. Here, we conducted a systematic review of the most up-to-date evidence on the association between diet as a whole and MBD. METHODS: We considered as eligible for inclusion in our review (PROSPERO registration code CRD42022335289) the studies published until 31 December 2021, that reported on the association between a priori or a posteriori dietary patterns (in observational studies) or dietary interventions (in randomized controlled trials) and MBD. RESULTS: In total, twelve studies were included. MBD tended to be inversely associated with adherence to dietary patterns characterized by high consumption of plant-based foods and low in meat, animal fats, and alcohol, defined both a priori (e.g., Mediterranean diet and WCRF/AICR guidelines) or a posteriori (e.g., "fruit-vegetable-cereal" and "salad-sauce-pasta/grains" patterns). Findings from intervention studies were in fair agreement with those from observational studies. CONCLUSIONS: While further studies are needed, we found suggestive evidence that the adoption of a healthy diet is associated with lower MBD.

The Prognostic Impact of Quitting Smoking at or around Diagnosis on the Survival of Patients with Gastrointestinal Cancers: A Systematic Literature Review.

Cigarette smoking is a strong risk factor for the occurrence of gastrointestinal cancers, and a substantial proportion of newly diagnosed patients is made up of active smokers, yet the impact of smoking cessation at or around diagnosis on the clinical course of these cancers (whose prognosis is often unfavourable) has never been summarized to date. We reviewed studies published until 30 April 2022 that investigated whether smoking cessation at or around diagnosis favourably affects the clinical course of gastrointestinal cancers patients. Six studies were included for colorectal cancer patients, which provided limited yet suggestive evidence that quitters may have longer disease-specific survival compared to continued smokers. Only one study each focused on patients with gastric or HBV-positive liver cancer (both reporting a survival advantage for quitters vs. continued smokers), while we found no eligible studies for patients with cancer at other sites within the digestive system. More research is urgently needed to expand the evidence on the topic, given the potentially major clinical implications for these patients. Moreover, health professionals should provide the necessary smoking cessation support to any smoker who is undergoing diagnostic work-up or treatment for gastrointestinal cancer.

A Priori Dietary Patterns, Physical Activity Level, and Body Composition in Postmenopausal Women: A Cross-Sectional Study.

Midlife weight gain and fat distribution changes increase the risk of age-related pathologies. We aimed to explore, in a series of 388 healthy postmenopausal women living in Tuscany, Central Italy, the relationship between three a priori dietary patterns, the level of physical activity (PA), and four body composition measures: body mass index (BMI), percent fat mass (%FM), percent muscle mass (%MM), and waist circumference (WC). Detailed information on lifestyle, including the amount of recreational and household PA, sitting time, and dietary habits were collected through detailed questionnaires, and adherence scores to Greek Modified Mediterranean Diet, Italian Mediterranean Diet (IMD), and Dietary Approaches to Stop Hypertension diet were calculated. The %FM and %MM were estimated via TANITA MC-780MA analyzer. WC and BMI were measured according to standard international protocols. Cross-sectional adjusted regression models showed that increasing adherence to IMD was inversely associated with BMI, %FM, and WC, and directly associated with %MM. Higher levels of recreational PA were associated with lower %FM, BMI, and WC and with higher %MM values. Higher levels of sitting time were associated with higher %FM, BMI, and WC, and lower %MM. Dietary habits and moderate PA confirm their central role in maintaining good health even in menopausal women.

The DAMA25 Study: Feasibility of a Lifestyle Intervention Programme for Cancer Risk Reduction in Young Italian Women with Breast Cancer Family History.

BACKGROUND: Diet and physical activity (PA) can modulate sporadic and possibly familial breast cancer (BC) risk. The DAMA25 study is a single-arm 12-month intervention aimed to modify dietary and PA habits in healthy young Italian women with a positive BC family history, categorized as having intermediate or high genetic risk according to NICE (National Institute for Health and Cancer Excellence) guidelines. METHODS: Participants, aged 25-49 years, were asked to adopt a diet mainly based on plant-based foods and to increase moderate daily activities combined with 1 h/week of more intense activity. Cooking lessons, collective walks, educational sessions, brochures, booklets and online materials were implemented. Dietary, PA habits and anthropometry were collected at baseline and at the end of the intervention. Changes on dietary, lifestyle habits and anthropometry were evaluated by GLM adjusted for weight reduction counselling aimed to participant with a BMI ≥ 25, age and baseline values of each variable. RESULTS: Out of 237 eligible women 107 (45.2%) agreed to participate and among them 98 (91.6%) completed the intervention. The adherence rate of the intervention was 77.8%. We observed a reduction in red and processed meat (p < 0.0001) and cakes consumption (p < 0.0001). Consumption of whole grain bread (p < 0.001), leafy vegetables (p = 0.01) and olive oil (p = 0.04) increased. We observed an increase in moderate (p < 0.0001) and more intense (p < 0.0001) recreational activities, an average 1.4 kg weight loss (p = 0.005), a reduction of waist circumference (p < 0.001) and fat mass (p = 0.015). CONCLUSIONS: The DAMA25 study shows that it is feasible an intervention to improve in the short-term dietary and PA habits and anthropometry in women with high BC familial risk.

DNA methylation-based biomarkers of aging were slowed down in a two-year diet and physical activity intervention trial: the DAMA study.

Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting increasingly accurate in predicting the individual biological age. The recently developed "next-generation clock" DNAmGrimAge outperforms "first-generation clocks" in predicting longevity and the onset of many age-related pathological conditions and diseases. Additionally, the total number of stochastic epigenetic mutations (SEMs), also known as the epigenetic mutation load (EML), has been proposed as a complementary DNAm-based biomarker of healthy aging. A fundamental biological property of epigenetic, and in particular DNAm modifications, is the potential reversibility of the effect, raising questions about the possible slowdown of epigenetic aging by modifying one's lifestyle. Here, we investigated whether improved dietary habits and increased physical activity have favorable effects on aging biomarkers in healthy postmenopausal women. The study sample consists of 219 women from the "Diet, Physical Activity, and Mammography" (DAMA) study: a 24-month randomized factorial intervention trial with DNAm measured twice, at baseline and the end of the trial. Women who participated in the dietary intervention had a significant slowing of the DNAmGrimAge clock, whereas increasing physical activity led to a significant reduction of SEMs in crucial cancer-related pathways. Our study provides strong evidence of a causal association between lifestyle modification and slowing down of DNAm aging biomarkers. This randomized trial elucidates the causal relationship between lifestyle and healthy aging-related epigenetic mechanisms.

Prediagnostic circulating metabolites in female breast cancer cases with low and high mammographic breast density.

Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We designed a matched case-case study in the EPIC Florence cohort, to evaluate possible associations between the pre-diagnostic metabolomic profile and the risk of BC in high- versus low-MBD women who developed BC during the follow-up. A case-case design with 100 low-MBD (MBD ≤ 25%) and 100 high-MDB BC cases (MBD > 50%) was performed. Matching variables included age, year and type of mammographic examination. 1H NMR metabolomic spectra were available for 87 complete case-case sets. The conditional logistic analyses showed an inverse association between serum levels of alanine, leucine, tyrosine, valine, lactic acid, pyruvic acid, triglycerides lipid main fraction and 11 VLDL lipid subfractions and high-MBD cases. Acetic acid was directly associated with high-MBD cases. In models adjusted for confounding variables, tyrosine remained inversely associated with high-MBD cases while 3 VLDL subfractions of free cholesterol emerged as directly associated with high-MBD cases. A pathway analysis showed that the "phenylalanine, tyrosine and tryptophan pathway" emerged and persisted after applying the FDR procedure. The supervised OPLS-DA analysis revealed a slight but significant separation between high- and low-MBD cases. This case-case study suggested a possible role for pre-diagnostic levels of tyrosine in modulating the risk of BC in high- versus low-MBD women. Moreover, some differences emerged in the pre-diagnostic concentration of other metabolites as well in the metabolomic fingerprints among the two groups of patients.

Time Course and Determinants of Individual Motivation among Women Enrolled in a Diet and Physical Activity Primary Prevention Trial.

We studied the determinants of motivation among post-menopausal women enrolled in a two-year diet and physical activity primary prevention randomized trial. Participants were requested to grade the importance attached to changing their lifestyle, their confidence about being able to implement the change, and their willingness to be involved in studies focusing on lifestyle. We used multi-adjusted regression to investigate the association between individual characteristics, study arm, and individual motivation at study entry and end. Participants (n = 234) were highly motivated both at entry and throughout the study. Women with pre-existing healthier eating habits and lifestyles (e.g., high consumption of fruit and vegetables, low red meat consumption, and physically active) were more motivated at entry and over the course of the study. Women assigned to any intervention arm were more motivated than those in the control arm. These findings may help enhance adherence to recommendations and improve effectiveness of community-based health promotion campaigns.

Alcohol, smoking and rectal cancer risk in a Mediterranean cohort of adults: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Italy cohort.

OBJECTIVE: Colorectal cancer (CRC) is one of the most diagnosed malignant cancers worldwide. Rectal cancers (Rcs) represent one-third of all CRCs. Cigarette smoking and alcohol drinking are two underestimated risk factors for RC. We aimed to evaluate the role of alcohol consumption and cigarette smoking in modulating RC risk and to estimate the attributable fraction in a Mediterranean population. METHODS: In the Italian section of the European Prospective Investigation into Cancer and Nutrition, 45,553 healthy adults (31,252 women) were recruited and provided information about lifestyle and dietary habits. During 14.0 years of median follow-up, 154 incident RC cases were identified. RESULTS: In multivariate models, a increase in RC risk emerged among subjects drinking more than 3 drinks/day, overall (hazard ratio [HR] = 1.74; 95% confidence interval [CI] 1.08-2.80), and in females (HR= 2.80; 95% CI 1.23-6.35), compared with drinkers of less than 1 drink/day. A increase in risk also emerged for current- compared with never-smokers, overall (HR = 1.57; 95% CI 1.06-2.35; P for trend 0.03) and among males (HR = 2.04; 95% CI 1.02-4.07; P for trend 0.045). Overall, 9% (95% CI 4-14%) of RC cases were attributable to drinking more than 3 drinks/day and 12% (95% CI 3-19%) were attributable to current smoke and 20% (95% CI 11-27%) of RC cases were attributable to the independent effects of these two exposures. CONCLUSION: Our study supports a strategy to avoid a relevant proportion of rectal cancer cases through a combined reduction of alcohol consumption and cigarette smoking.

Determinants of Erythrocyte Lead Levels in 454 Adults in Florence, Italy.

Background: Lead exposure, even at low levels, is associated with adverse health effects in humans. We investigated the determinants of individual lead levels in a general population-based sample of adults from Florence, Italy. Methods: Erythrocyte lead levels were measured (using inductively coupled plasma-mass spectrometry) in 454 subjects enrolled in the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study in 1992⁻1998. Multiple linear regression models were used to study the association between demographics, education and working history, lifestyle, dietary habits, anthropometry, residential history, and (among women) menstrual and reproductive history and use of exogenous sex hormones, and erythrocyte lead levels. Results: Median lead levels were 86.1 µg/L (inter-quartile range 65.5⁻111.9 µg/L). Male gender, older age, cigarette smoking and number of pack-years, alcohol intake, and residing in urban areas were positively associated with higher erythrocyte lead levels, while performing professional/managerial or administrative work or being retired was inversely associated with lead levels. Among women, lead levels were higher for those already in menopause, and lower among those who ever used hormone replacement therapy. Conclusions: Avoidable risk factors contribute to the lead body burden among adults, which could therefore be lowered through targeted public health measures.

Can Dietary and Physical Activity Modifications Reduce Breast Density in Postmenopausal Women? The DAMA Study, a Randomized Intervention Trial in Italy.

BACKGROUND: Few randomized trials have been carried out to evaluate the effect of lifestyle modifications on mammographic breast density (MBD). The randomized 2 × 2 factorial Diet, physical Activity and MAmmography trial aimed to evaluate whether MBD can be reduced in postmenopausal women with high baseline MBD by a 24-month dietary and/or physical activity (PA) interventions. METHODS: We randomized healthy postmenopausal women, attending the Florence (Italy) mammographic screening program, ages 50 to 69 years, nonsmokers, with MBD > 50% and no recent hormone therapy, to (i) a dietary intervention focused on plant foods, with a low glycemic load, low in saturated fats and alcohol; (ii) a PA intervention combining daily moderate intensity activities and one weekly supervised session of more strenuous activity; (iii) both interventions; (iv) general recommendations. We evaluated changes in MBD based on Volpara estimates comparing baseline and follow-up digital mammograms by an intention-to-treat-analysis. RESULTS: MBD measures were available for 226 participants. An interaction emerged between treatments and thus we run analyses by arms. A decrease in volumetric percent density emerged for women in the dietary intervention (ratio 0.91; 95% CI, 0.86-0.97; P = 0.002) and in the PA intervention arm (0.93; 95% CI, 0.87-0.98; P = 0.01) in comparison with controls. No clear effect emerged in the double intervention arm. CONCLUSIONS: This intervention trial suggests that a 24-month dietary or PA intervention may reduce MBD in postmenopausal women. IMPACT: A modification of dietary habits or an increase in PA in postmenopausal women may reduce MBD. Further studies are needed to confirm these findings for planning breast cancer preventive strategies.

Adherence to a Mediterranean diet and long-term changes in weight and waist circumference in the EPIC-Italy cohort.

Excessive calorie intake and physical inactivity are considered key determinants of the rapid worldwide increase in obesity prevalence, however the relationship between diet and weight gain is complex. We investigated associations between adherence to a Mediterranean diet and long-term changes in weight and waist circumference in volunteers recruited to the Italian section of the prospective European Prospective Investigation into Cancer and Nutrition (EPIC). We investigated 32,119 cohort members who provided anthropometric measures at recruitment and updated information on recall a mean of 12 years later. Adherence to a Mediterranean diet was assessed using the Italian Mediterranean Index (score range 0-11). Associations between index score and weight and waist changes were assessed by multivariate linear regression models. Risks of developing overweight/obesity and abdominal obesity were investigated by multivariate logistic models. Increasing Italian Mediterranean Index score (indicating better adherence) was associated with lower 5-year weight change in volunteers of normal weight at baseline (ß -0.12, 95% CI -0.16 to -0.08 for 1 tertile increase in score), but not in those overweight/obese at baseline (P interaction between Index score and BMI 0.0001). High adherence was also associated with reduced risk of becoming overweight/obese (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile); smaller 5-year change in waist circumference (ß -0.09, 95% CI -0.14 to -0.03 for 1 tertile increase in score); and lower risk of abdominal obesity (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile). Adherence to a traditional Italian Mediterranean diet may help prevent weight gain and abdominal obesity.

Mammographic breast density and breast cancer risk in a Mediterranean population: a nested case-control study in the EPIC Florence cohort.

PURPOSE: Mammographic breast density (MBD) has been consistently associated with breast cancer (BC) risk, and at the same time it is modulated by established BC risk factors related to reproductive and hormonal history and to lifestyle. We aimed to evaluate the association between the clinical breast imaging reporting and data system (BI-RADS), a qualitative MBD classification used in clinical setting, and BC risk through a case-control nested in the EPIC Florence cohort where baseline information on reproductive history, lifestyle and anthropometry were collected. METHODS: The study includes 136 newly diagnosed BC cases and 635 controls from the 10,083 healthy women enroled in the cohort between 1993 and 1998 and followed for 6 years on average. MBD was assessed on a negative mammogram performed at least one year before diagnosis in cases and on a mammogram performed in the same period for controls matched for age, enrolment date and menopausal status. Multivariate analyses adjusted for education, body mass index, parity, number of children, breastfeeding, BC family history, history of breast biopsies and Hormone Replacement Therapy use were performed. RESULTS: An increase in BC risk across BI-RADS categories emerged with adjusted odds ratios (OR) 1.79 (95% CI 1.06-3.01), OR 2.09 (95% CI 1.17-3.74) and OR 2.67 (95% CI 1.08-6.62) for categories 2, 3 and 4 in comparison with the reference category (p for trend = 0.008). CONCLUSIONS: We confirm in this Mediterranean population the association of increasing MBD, classified according to BI-RADS with BC risk also taking into account other well-known risk factors for this neoplasm.

Low back pain in healthy postmenopausal women and the effect of physical activity: A secondary analysis in a randomized trial.

Epidemiological studies on the prevalence of musculoskeletal pain have consistently shown that this is a relevant health problem, with non-specific low back pain (LBP) being the most commonly reported in adult females. Conflicting data on the association between LBP symptoms and physical activity (PA) have been reported. Here, we investigated the prevalence of LBP and the effect of a 24-month non-specific PA intervention on changes in LBP prevalence in a series of Italian healthy postmenopausal women. We performed a secondary analysis in the frame of the DAMA trial, a factorial randomized intervention trial aimed to evaluate the ability of a 24-month intervention, based on moderate-intensity PA, and/or dietary modification, in reducing mammographic breast density in healthy postmenopausal women. The PA intervention included at least 1 hour/day of moderate PA and a more strenuous weekly activity, collective walks and theoretical group sessions. A self-administered pain questionnaire was administered at baseline and at the end of the intervention. The questionnaire was specifically structured to investigate the occurrence of musculoskeletal pain, the body localization, intensity and duration of the pain. Two hundred and ten women (102 randomized to PA intervention, 108 not receiving the PA intervention) filled out the questionnaires. At baseline LBP was present in 32.9% of the participants. Among women randomized to the PA intervention, LBP prevalence at follow up (21.6%) was lower than at baseline (33.3%) (p = 0.02), while in women who did not receive the PA intervention the LBP prevalence at baseline and follow up were 32.4% and 25.9%, respectively (p = 0.30). Overall, there was no significant between-group effect of PA intervention on LBP. Further studies are needed to understand the role of non-specific PA intervention, aimed to improve overall fitness, on LBP prevalence.