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Resistance Exercise Training Increases Muscle Mass and Strength in Prostate Cancer Patients on Androgen Deprivation Therapy.
Houben, LHP, Overkamp, M, VAN Kraaij, P, Trommelen, J, VAN Roermund, JGH, DE Vries, P, DE Laet, K, VAN DER Meer, S, Mikkelsen, UR, Verdijk, LB, et al
Medicine and science in sports and exercise. 2023;55(4):614-624
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Androgen deprivation therapy (ADT) forms the cornerstone in the treatment of localised high-risk, locally advanced, and metastatic prostate cancer (PCa). The hypothesis of this study was that protein supplementation augments the benefits of prolonged resistance exercise training to attenuate the decline in muscle mass, reduce fat mass accrual, and increase strength and physical performance in PCa patients on ADT. This study is a multicentre partly randomised controlled trial, comparing two intervention groups with a separately recruited control group. One hundred and twenty-six patients were included, and ninety-six patients finished the study. Results show that 20 week of resistance exercise training was feasible, safe, and well tolerated, and effectively counteracted the negative effect of ADT treatment on body composition, muscle mass, leg strength, and aerobic capacity in men with advanced PCa. Protein supplementation did not further augment the benefits of resistance exercise training. Authors conclude that protein supplementation is not required to further augment gains in muscle mass and strength after resistance exercise training in PCa patients who habitually consume ample protein.
Abstract
PURPOSE This study aimed to assess the effects of 20 wk resistance exercise training with or without protein supplementation on body composition, muscle mass, muscle strength, physical performance, and aerobic capacity in prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS Sixty prostate cancer patients receiving ADT were randomly assigned to perform 20 wk of resistance exercise training with supplementation of 31 g whey protein (EX + PRO, n = 30) or placebo (EX + PLA, n = 30), consumed immediately after exercise and every night before sleep. A separate control group (CON, n = 36) only received usual care. At baseline and after 20 wk, body composition (dual-energy x-ray absorptiometry), muscle mass (computed tomography scan), muscle strength (1-repetition maximum strength tests), physical performance (Timed Up and Go Test, 30-Second Chair Stand Test, and Stair Climb Test), aerobic capacity (cardiopulmonary exercise test), and habitual dietary intake (food diary) were assessed. Data were analyzed using a two-factor repeated-measures ANOVA. RESULTS Over time, muscle mass and strength increased in EX + PRO and EX + PLA and decreased in CON. Total fat mass and fat percentage increased in EX + PRO and CON, but not in EX + PLA. Physical performance did not significantly change over time in either group. Aerobic capacity was maintained in EX + PLA, but it decreased in EX + PRO and CON. Habitual protein intake (without supplements) averaged >1.0 g·kg body weight -1 ·d -1 , with no differences over time or between groups. CONCLUSIONS In prostate cancer patients, resistance exercise training counteracts the adverse effects of ADT on body composition, muscle mass, muscle strength, and aerobic capacity, with no additional benefits of protein supplementation.
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Impact of a ketogenic diet intervention during radiotherapy on body composition: V. Final results of the KETOCOMP study for head and neck cancer patients.
Klement, RJ, Sweeney, RA
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 2022;198(11):981-993
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Head and neck cancer (HNC) describes cancers originating from the lip, oral and nasal cavity, paranasal sinuses, pharynx, larynx, and trachea. Patients with HNC frequently present with feeding difficulties and malnutrition, which are often further aggravated by tobacco and alcohol abuse and a general unhealthy lifestyle. This study aimed to investigate the impact of a ketogenic diet (KD) versus an unspecified standard diet (SD) on body composition and survival in HNC patients undergoing radio(chemo)therapy. This study is a controlled clinical trial. Results show that an individualized KD supplemented with essential amino acids consumed during curative radio(chemo)therapy of HNC patients was able to slow down the negative consequences of therapy on body composition to some extent. Authors conclude that further research of KDs in frail cancer patient populations is required which may help to motivate their implementation as complementary therapies for select patients.
Abstract
PURPOSE Patients with head and neck cancer (HNC) are at risk of malnutrition, especially during radiochemotherapy. We aimed to study the impact of a ketogenic diet (KD) versus an unspecified standard diet (SD) on body composition and survival in HNC patients undergoing radio(chemo)therapy. METHODS As part of a controlled clinical trial, non-metastasized HNC patients were enrolled into either a KD (N = 11) or an SD (N = 21) group between May 2015 and May 2021. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Overall and progression-free survival was assessed during regular follow-up. RESULTS A total of 7 KD and 21 SD patients completed the study and were eligible for comparative analysis. Chemotherapy was significantly associated with declines in all body composition parameters, while the KD had opposing, yet nonsignificant effects. In patients receiving chemotherapy, average weekly reductions of body mass (BM) and skeletal muscle mass (SMM) were 0.9 kg and 0.31 kg in the KD group versus 1.2 kg and 0.57 kg in the SD group, respectively. Patients in the KD group receiving no chemotherapy achieved an average increase of 0.04 kg BM and 0.12 kg SMM per week. After a median follow-up of 42 months (range 6.7-78 months) there were no significant differences in progression-free or overall survival between the groups. CONCLUSION The KD may partially counteract the detrimental effects of radiochemotherapy on body composition in HNC patients. This should encourage further research into KDs in frail cancer patient populations and motivate their implementation as complementary therapy for selected patients.
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Mediterranean Style Dietary Pattern with High Intensity Interval Training in Men with Prostate Cancer Treated with Androgen Deprivation Therapy: A Pilot Randomised Control Trial.
Baguley, BJ, Adlard, K, Jenkins, D, Wright, ORL, Skinner, TL
International journal of environmental research and public health. 2022;19(9)
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The use of androgen deprivation therapy (ADT) has coincided with improvements in disease control and improved overall survivorship in many men treated for prostate cancer. Exercise and nutrition interventions during and/or after ADT are strongly recommended to mitigate or improve body composition and reduce cardiometabolic side effects. The aim of this study was to examine the combined effects of a Mediterranean diet (MED-diet) and high intensity interval training (HIIT) on cardiorespiratory fitness, body composition and quality of life, compared to usual care, in men with prostate cancer treated with ADT. This study is a two-arm randomised controlled trial. Participants (n = 23) were randomly allocated to either an intervention or usual care group in a 1:1 ratio. Results show that for men with prostate cancer undergoing ADT, a MED-diet with HIIT compared to usual care at 20 weeks (i) significantly improved cardiorespiratory fitness relative; (ii) reduced body weight; (iii) maintained lean body mass despite achieving weight loss; (iv) significantly improved vitality and mental health composite, and clinical improvements were seen in prostate-cancer specific quality of life and cancer-related fatigue. Authors conclude that future larger-scale trials examining the MED-diet with HIIT on cardiorespiratory fitness, body composition and quality of life would help to extend the findings of their study.
Abstract
Background: Androgen deprivation therapy (ADT) in prostate cancer has been shown to deteriorate body composition (reduced lean mass and increased body and fat mass) and increase the risk of cardiovascular morbidity. The Mediterranean style dietary pattern (MED-diet) and high intensity interval training (HIIT) may synergistically alleviate these side effects and improve quality of life in men treated with ADT. Methods: Twenty-three men (65.9 ± 7.8 years; body mass index: 29.6 ± 2.7 kg/m2; ADT duration: 33.8 ± 35.6 months) receiving ADT for ≥3 months were randomly assigned (1:1) to 20 weeks of usual care or the MED-diet (10 nutrition consults) with HIIT (4 × 4 min 85−95% heart rate peak, 3× week, starting at 12 weeks). Results: The MED-diet with HIIT significantly improved cardiorespiratory fitness (+4.9 mL·kg−1·min, p < 0.001), and body mass (−3.3 kg, p < 0.001) compared to the usual care group at 20 weeks. Clinically meaningful (≥3 points) improvements were seen in quality of life and cancer-related fatigue after 20 weeks. Conclusions: The MED-diet with HIIT increased cardiorespiratory fitness and reduced body weight in men with prostate cancer treated with ADT. Larger trials determining whether the MED-diet with HIIT translates to cardiovascular benefits are warranted.
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A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.
Basak, SK, Bera, A, Yoon, AJ, Morselli, M, Jeong, C, Tosevska, A, Dong, TS, Eklund, M, Russ, E, Nasser, H, et al
Cancer. 2020;126(8):1668-1682
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APG-157 is a botanical drug containing multiple polyphenols that delivers the active components to oromucosal tissues near the tumour target. APG-157 slowly disintegrates in the oral cavity over 15 to 20 minutes to release the drug substance. The drug substance is a precise, rational combination of multiple molecules derived from Curcuma longa wherein curcumin is the principal component. The main aim of this study was to determine the pharmacokinetics and safety of the orally delivered pastille (APG-157) when used by normal subjects and patients with cancer. This study is a randomised, double-blind, placebo-controlled trial. A total of 32 subjects were enrolled, and 25 completed the study (13 normal individuals and 12 patients with oral cancer). Results demonstrated that transoral APG-157 treatment leads to systemic absorption of curcumin and its analogs. There was a statistically significant concentration reduction in inflammatory cytokines and Bacteroides species noted in the salivary cells. Pre-treatment and post-treatment tumour samples from patients with cancer demonstrated T-cell recruitment to the tumour microenvironment. Authors conclude that APG-157 is absorbed well, reduces inflammation, and attracts T-cells to the tumour thus, it can be potentially used in combination with immunotherapy drugs. Furthermore, a long-term evaluation of immune checkpoint blockade with and without APG-157 could provide a clear understanding of the usefulness of APG-157 as either an adjuvant or neoadjuvant therapeutic agent for patients with advanced or recurrent head and neck cancer.
Abstract
BACKGROUND Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target. METHODS A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity. RESULTS Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment. CONCLUSIONS The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy. LAY SUMMARY Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
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Effects of Fasting on 18F-DCFPyL Uptake in Prostate Cancer Lesions and Tissues with Known High Physiologic Uptake.
Wondergem, M, van der Zant, FM, Vlottes, PW, Knol, RJJ
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;59(7):1081-1084
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Prostate-specific membrane antigen (PSMA) (PSMA is a type II membrane protein)–targeted PET imaging is being increasingly applied in prostate cancer. The aim of this study was to determine the impact of fasting on 18F-DCFPyL (is a fluorine-18 labelled ligand binding specifically to PSMA) uptake in organs with known high physiologic uptake and in lesions characteristic of prostate cancer metastases. The study is a cohort study in which 50 and 48 patients were analysed in the fasting and non-fasting cohorts, respectively. Results showed that lesions characteristic of prostate cancer showed similar uptake in both the fasting and the non-fasting cohorts (number of lesions characteristic of prostate cancer totalled to 152 and 131 respectively). Authors conclude that fasting for up to 6 h before 18F-DCFPyL PET/CT does not significantly affect uptake in suspected malignant lesions but significantly lowers uptake in tissues with high physiologic uptake, such as the salivary glands, liver, and spleen.
Abstract
In the literature, a 4- to 6-h fast is recommended before a patient undergoes PET/CT with 2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL); however, a scientific underpinning for this recommendation is lacking. Therefore, we performed a study to determine the impact of fasting on 18F-DCFPyL uptake. Methods: The study included 50 patients who fasted at least 6 h before 18F-DCFPyL administration and 50 patients who did not. Activity (SUVmax) was measured in lesions characteristic of prostate cancer and in normal tissues known to express high physiologic uptake. Results: Uptake in suspected lesions did not differ between the cohorts. 18F-DCFPyL uptake in the submandibular gland, liver, and spleen was significantly higher in the fasting than the nonfasting cohort. Conclusion: Our data show that fasting does not significantly affect 18F-DCFPyL uptake in suspected malignant lesions but does result in significantly lower 18F-DCFPyL uptake in tissues with high physiologic uptake. The absolute differences in uptake were relatively small; therefore, the effects of fasting on the diagnostic performance can be considered negligible.
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Exercise Preserves Physical Function in Prostate Cancer Patients with Bone Metastases.
Galvão, DA, Taaffe, DR, Spry, N, Cormie, P, Joseph, D, Chambers, SK, Chee, R, Peddle-McIntyre, CJ, Hart, NH, Baumann, FT, et al
Medicine and science in sports and exercise. 2018;50(3):393-399
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Existing research indicates cancer patients with bone metastases should not participate in exercise due to potential risks to the skeletal system. However, current oncology guidelines suggest that all cancer patients should avoid inactivity, including those with bone metastases. The purpose of this study is to determine the safety and efficacy of exercise among 57 prostate cancer patients with bone metastases. Participants were randomised to either participate in exercise or receive usual care for three months. Exercise consisted of supervised aerobic activity, resistance training and stretching three days a week. Overall health status and physical function was measured by self-reported questionnaire. This study found self-reported physical functioning and lower muscle strength was improved significantly in the exercise group. There were no difference in bone pain between groups, and no adverse events occurred. Based on these results, the authors conclude exercise is safe and can help improve physical functioning among prostate cancer patients with bone metastasis.
Abstract
PURPOSE The presence of bone metastases has excluded participation of cancer patients in exercise interventions and is a relative contraindication to supervised exercise in the community setting because of concerns of fragility fracture. We examined the efficacy and safety of a modular multimodal exercise program in prostate cancer patients with bone metastases. METHODS Between 2012 and 2015, 57 prostate cancer patients (70.0 ± 8.4 yr; body mass index, 28.7 ± 4.0 kg·m) with bone metastases (pelvis, 75.4%; femur, 40.4%; rib/thoracic spine, 66.7%; lumbar spine, 43.9%; humerus, 24.6%; other sites, 70.2%) were randomized to multimodal supervised aerobic, resistance, and flexibility exercises undertaken thrice weekly (EX; n = 28) or usual care (CON; n = 29) for 3 months. Physical function subscale of the Medical Outcomes Study Short-Form 36 was the primary end point as an indicator of patient-rated physical functioning. Secondary end points included objective measures of physical function, lower body muscle strength, body composition, and fatigue. Safety was assessed by recording the incidence and severity of any adverse events, skeletal complications, and bone pain throughout the intervention. RESULTS There was a significant difference between groups for self-reported physical functioning (3.2 points; 95% confidence interval, 0.4-6.0 points; P = 0.028) and lower body muscle strength (6.6 kg; 95% confidence interval, 0.6-12.7; P = 0.033) at 3 months favoring EX. However, there was no difference between groups for lean mass (P = 0.584), fat mass (P = 0.598), or fatigue (P = 0.964). There were no exercise-related adverse events or skeletal fractures and no differences in bone pain between EX and CON (P = 0.507). CONCLUSIONS Multimodal modular exercise in prostate cancer patients with bone metastases led to self-reported improvements in physical function and objectively measured lower body muscle strength with no skeletal complications or increased bone pain. TRIAL REGISTRATION ACTRN12611001158954.
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Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.
Cooke, GE, Wetter, NC, Banducci, SE, Mackenzie, MJ, Zuniga, KE, Awick, EA, Roberts, SA, Sutton, BP, McAuley, E, Kramer, AF
PloS one. 2016;11(2):e0149552
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As survival rates of breast cancer increase, the long-term cognitive effects of disease and required treatment are emerging. The underlying pathways of cancer-related cognitive impairment involve accelerated aging of the brain, low levels of physical activity and decreased cognitive function, however these links have not been adequately explored. The aim of this study was to investigate the link between physical activity, white matter lesion volume and cognition in 30 breast cancer survivors and 28 age-matched controls. The results of this study showed that brain structure significantly predicted cognitive function. This study provided evidence suggesting that moderate physical activity may help reduce the treatment related risks associated with breast cancer.
Abstract
Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.
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Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Demark-Wahnefried, W, Nix, JW, Hunter, GR, Rais-Bahrami, S, Desmond, RA, Chacko, B, Morrow, CD, Azrad, M, Frugé, AD, Tsuruta, Y, et al
BMC cancer. 2016;16:61
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There is a strong body of evidence associating obesity and increased risk for more aggressive and progressive cancer. This paper aims to assess the feasibility of a presurgical diet and exercise weight loss intervention in men with newly-diagnosed prostate cancer who elected for prostatectomy. It also aims to explore the intervention’s effects on tumour proliferation rates and other biomarkers. The 3-weeks randomised controlled study included 40 overweight or obese men newly-diagnosed with prostate cancer. Participants in experimental arm were assigned to a healthy energy-restricted diet versus wait-list control arm. All feasibility endpoints were achieved with accrual completed within 2 years, retention of 85%, adherence of 95% and no adverse events. Biologic outcomes were not included in this paper, as biological testing was still ongoing. Authors concluded that this study’s methods and data on feasibility could provide useful framework for the design of future trials. They also highlighted the importance of presurgical trials as a feasible and safe means to assess the impacts of diet and exercise on tumour tissue.
Abstract
BACKGROUND Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION NCT01886677.
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Adolescent diet and subsequent serum hormones, breast density, and bone mineral density in young women: results of the Dietary Intervention Study in Children follow-up study.
Dorgan, JF, Liu, L, Klifa, C, Hylton, N, Shepherd, JA, Stanczyk, FZ, Snetselaar, LG, Van Horn, L, Stevens, VJ, Robson, A, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2010;19(6):1545-56
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Population and animal studies suggest that fat in the diet may have an influence on the development of breast cancer, but the results of studies in humans are inconsistent. This randomised controlled trial aimed to determine the effects of a lower-fat diet during childhood and adolescence on markers associated with breast cancer risk in adults. Female participants were initially recruited at age 8-10 years old, as part of a study to test the effects of lower-fat diets on cholesterol levels in children. The study diet limited total fat intake to 28% of calories (<8% saturated fat, <9% polyunsaturated fat, remainder monounsaturated), cholesterol was limited to 150mg/day and consumption of fibre was encouraged. The children followed the diet for 7 years, when the trial was terminated. This follow-up study was conducted 9 years later, when the participants were aged 25 to 29 years old. After adjusting for current diet, the lower-fat diet group had significantly higher oestradiol levels and bone mineral density. Progesterone concentrations and breast density did not differ between the two groups. The authors concluded that consumption of a lower-fat diet during adolescence does not appear to affect factors associated with breast cancer risk. Current diet may be more important than adolescent diet in determining hormone levels in premenopausal women.
Abstract
BACKGROUND Adolescent diet is hypothesized to influence breast cancer risk. We evaluated the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults. METHODS A follow-up study was conducted on 230 girls who participated in the Dietary Intervention Study in Children (DISC), in which healthy, prepubertal, 8 to 10 year olds were randomly assigned to usual care or to a behavioral intervention that promoted a reduced fat diet. Participants were 25 to 29 years old at follow-up visits. All tests of statistical significance are two-sided. RESULTS In analyses that did not take account of diet at the time of the follow-up visit, the only statistically significant treatment group difference was higher bone mineral content in intervention group participants compared with usual care group participants; their mean bone mineral contents were 2,444 and 2,377 g, respectively. After adjustment for current diet, the intervention group also had statistically significantly higher bone mineral density and luteal phase serum estradiol concentrations. Serum progesterone concentrations and breast density did not differ by treatment group in unadjusted or adjusted analyses. CONCLUSIONS Results do not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density, or bone mineral density. It remains unclear, however, if the results are specific to the DISC intervention or are more broadly applicable. IMPACT Modest reductions in fat intake during adolescence are unlikely to lower later breast cancer risk via long-term effects on the biomarkers measured.