A Scoping Review to Explore the Potential Benefits of Nutrition Interventions for Latino/a Adult Cancer Survivors in the US.

Despite evidence for the role of healthy diets in preventing cancer, little is known about how nutrition can support positive health outcomes after a cancer diagnosis for Latino/a cancer survivors in the United States (U.S.). The purpose of this scoping review is to understand the potential benefits of nutrition interventions in supporting healthy survivorship among Latino/a cancer survivors in the U.S. A team compiled, evaluated, and summarized the available evidence. Potentially relevant studies were identified from a comprehensive search of peer-reviewed databases and the gray literature. Eligible studies included Latino/a adult cancer survivors with a nutrition education, dietary change, or behavioral intervention; and a nutrition-related health outcome. Data were extracted and summarized using tables. The review included 10 randomized controlled trials, with samples or subsamples of Latino/a cancer survivors. Interventions mostly focused on breast cancer survivors. The results showed some evidence that dietary behaviors, like fruit and vegetable intake, were related to positive outcomes, like a decreased risk of cancer (through changes in DNA methylation), decreased risk breast cancer recurrence (through changes in inflammatory biomarkers), or improved perception of health status. The findings highlight a need for community-engaged and culturally relevant nutrition interventions for Latino/a adults, especially for rural communities; and innovative intervention approaches, including m/ehealth approaches with long-term follow-up.

Influence of Olive Oil and Its Components on Breast Cancer: Molecular Mechanisms.

Breast cancer is the most frequent malignant neoplasia and a leading cause of mortality in women worldwide. The Mediterranean diet has been proposed as a healthy dietary pattern with protective effects in several chronic diseases, including breast cancer. This diet is characterized by the consumption of abundant plant foods and olive oil as the principal source of fat, which is considered one of the main components with potential antioxidant, anti-inflammatory and anticancer effects. Extra-virgin olive oil (EVOO) has several bioactive compounds, mainly including monounsaturated fatty acids, triterpenes and polyphenols, such as phenolic alcohols (e.g., hydroxytyrosol), secoiridoids (e.g., oleuropein and oleocanthal), lignans (e.g., pinoresinol) or flavonoids (e.g., luteolin). While epidemiological evidence is still limited, experimental in vivo and in vitro data have shown a protective effect of this oil and its compounds on mammary carcinogenesis. Such effects account through complex and multiple mechanisms, including changes in epigenetics, transcriptome and protein expression that modulate several signaling pathways. Molecular targets of EVOO compounds have a role in the acquisition of cancer hallmarks. Although further research is needed to elucidate their beneficial effects on human prevention and progression of the disease, evidence points to EVOO in the context of the Mediterranean diet as a heathy choice, while EVOO components may be promising adjuvants in anticancer strategies.

Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer.

In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor Th1/cytotoxic responses and an enrichment of IFNγ and other immune signatures associated with better clinical outcomes in patients with cancer. Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments. SIGNIFICANCE: Cyclic FMD is well tolerated and causes remarkable systemic metabolic changes in patients with different tumor types and treated with concomitant antitumor therapies. In addition, the FMD reshapes systemic and intratumor immunity, finally activating several antitumor immune programs. Phase II/III clinical trials are needed to investigate FMD antitumor activity/efficacy.This article is highlighted in the In This Issue feature, p. 1.

A high extra-virgin olive oil diet induces changes in metabolic pathways of experimental mammary tumors.

Breast cancer is the most common malignancy in women worldwide, and environmental factors, especially diet, have a role in the etiology of this disease. This work aimed to investigate the influence of high fat diets (rich in corn oil or extra virgin olive oil -EVOO-) and the timing of dietary intervention (from weaning or after induction) on tumor metabolism in a seven,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer model in rat. The effects of lipids (oils and fatty acids) have also been investigated in MCF-7 cells. The results have confirmed different effects on tumor progression depending on the type of lipid. Molecular analysis at mRNA, protein and activity level of enzymes of the main metabolic pathways have also shown differences among groups. Thus, the animals fed with the EVOO-enriched diet developed tumors with less degree of clinical and morphological malignancy and showed modified glucose and mitochondrial metabolism when compared to the animals fed with the corn oil-enriched diet. Paradoxically, no clear influence on lipid metabolism by the high fat diets was observed. Considering previous studies on proliferation and apoptosis in the same samples, the results suggest that metabolic changes have a role in the molecular context that results in the modulation of different signaling pathways. Moreover, metabolic characteristics, without the context of other pathways, may not reflect tumor malignancy. The time of dietary intervention plays also a role, suggesting the importance of metabolic plasticity and the relation with mammary gland status when the tumor is induced.

Nutraceuticals in the Mediterranean Diet: Potential Avenues for Breast Cancer Treatment.

The traditional Mediterranean Diet constitutes a food model that refers to the dietary patterns of the population living in countries bordering the Mediterranean Sea in the early 1960s. A huge volume of literature data suggests that the Mediterranean-style diet provides several dietary compounds that have been reported to exert beneficial biological effects against a wide spectrum of chronic illnesses, such as cardiovascular and neurodegenerative diseases and cancer including breast carcinoma. Among bioactive nutrients identified as protective factors for breast cancer, natural polyphenols, retinoids, and polyunsaturated fatty acids (PUFAs) have been reported to possess antioxidant, anti-inflammatory, immunomodulatory and antitumoral properties. The multiple anticancer mechanisms involved include the modulation of molecular events and signaling pathways associated with cell survival, proliferation, differentiation, migration, angiogenesis, antioxidant enzymes and immune responses. This review summarizes the anticancer action of some polyphenols, like resveratrol and epigallocatechin 3-gallate, retinoids and omega-3 PUFAs by highlighting the important hallmarks of cancer in terms of (i) cell cycle growth arrest, (ii) apoptosis, (iii) inflammation and (iv) angiogenesis. The data collected from in vitro and in vivo studies strongly indicate that these natural compounds could be the prospective candidates for the future anticancer therapeutics in breast cancer disease.

Zinc Affects Cholesterol Oxidation Products and Fatty Acids Composition in Rats' Serum.

The purpose of this work was to evaluate the effect of the nanosized or microsized zinc (Zn) particles on fatty acid profile, enzyme activity and the level of cholesterol, squalene and oxysterols in rats with breast cancer. Rats (female, n = 24) were divided into the following groups: control, and two test groups, whose diets were enriched with either Zn microparticles (342 nm) or Zn nanoparticles (99 nm). All rats were treated twice with the carcinogenic agent; 7,12-dimethylbenz[a]anthracene. In rats whose diet was enriched with zinc (especially in the form of nanoparticles), the number and sizes of tumors were lower. Diet supplementation also significantly reduced the cholesterol (p = 0.027) and COPs (cholesterol oxidation products) levels (p = 0.011) in rats serum. Enriching the diet with Zn microparticles decreased the Δ6-desaturase activity (p < 0.001). Zn influences fatty acids' profile in rats' serum as well as inhibiting desaturating enzymes. A reduced amount of pro-inflammatory arachidonic acid derivatives may be the expected effect.

Nutritional Intervention Contributes to the Improvement of Symptoms Related to Quality of Life in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: A Randomized Clinical Trial.

During breast cancer treatment, worsening quality of life (QoL) and the presence of toxicities are common, but healthy eating practices are associated with better clinical results. Thus, this study aims to evaluate the effect of a nutritional intervention on QoL and on gastrointestinal and hematological toxicities resulting from chemotherapy in women with breast cancer. A randomized clinical trial was performed at the beginning of neoadjuvant chemotherapy treatment for women with breast cancer. All participants received nutritional advice on healthy eating practices, but only the intervention group (IG) received an individualized diet plan. The study enrolled 34 women, 19 in the IG and 15 in the control group (CG). During the study, the CG significantly presented a reduction (from 21.6 ± 5.9 kg to 18.8 ± 4.0 kg, p = 0.009) in handgrip strength (HGS), while the IG did not present changes in this variable. Regarding QoL, the IG preserved the role function during treatment and presented better results for nausea/vomiting and loss of appetite compared to the CG. In gastrointestinal and hematological toxicities, the IG had lower frequencies of leukopenia and abdominal pain. The nutritional intervention preserved the role function of QoL and HGS, reduced the occurrence of nausea/vomiting, loss of appetite and the frequency of leukopenia and abdominal pain.

CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling.

BACKGROUND: Circular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC). MATERIALS AND METHODS: qRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10. RESULTS: CircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10. CONCLUSIONS: CircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients.

The anticarcinogen activity of ß-arbutin on MCF-7 cells: Stimulation of apoptosis through estrogen receptor-α signal pathway, inflammation and genotoxicity.

Arbutin is one of the active ingredients employed in cosmetics as a skin whitening agent. In the present study, the possible effects of arbutin on breast cancer were determined with human breast adenocarcinoma (MCF-7) cells. α and ß-arbutin cytotoxicity levels in MCF-7 cells were determined with the MTT method. At low (1-10 mM) doses, α-arbutin appears to be more toxic than ß-arbutin. At higher (5-200 mM) and LD50 doses beta arbutin toxicity appears to be higher than alpha arbutin. Thus, the study was continued with ß -arbutin. The effects of low and high doses of ß-arbutin was determined on oxidative stress, genotoxicity, inflammation, apoptosis, proliferation, endoplasmic reticulum stress and estrogen receptor-α in MCF-7 cells. The results demonstrated that the ß-arbutin doses administered to MCF-7 cells did not affect oxidative and endoplasmic reticulum stress in the experimental groups. However, it was found that administration of LD50 dose ß-arbutin induced inflammation in these cells via proinflammatory cytokine levels (TNF-α, IFN-γ and IL-1ß). It was observed that LD10 and LD50 doses of ß-arbutin increased genotoxicity in MCF-7 cells. The gene expression analysis conducted with RT-PCR device and immunocytochemical analysis revealed that ß-arbutin at LD50 dose induced apoptosis in MCF-7 cells via p53 and Caspase 3. Furthermore, it was determined that all ß-arbutin doses inhibited estrogen receptor-α in MCF-7 cells. Considering that arbutin increased the activation of apoptotic Caspase 3 through p53, which was stimulated by genotoxic and inflammatory effects at LD50 dose in MCF-7 cells. Determination of this mechanism behind these effects of ß-arbutin may contribute to the development of a new perspective in treatment.

Real-world Outcomes of Cyclin-dependent Kinase Inhibitors Continued Beyond First Disease Progression in Hormone Receptor-positive Metastatic Breast Cancer.

BACKGROUND: CDK4/6 inhibitors (CDK4/6i), in combination with aromatase inhibitors, are United States Food and Drug Administration-approved for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). The effectiveness of continuing them beyond first disease progression (PD) is currently unknown. This retrospective study evaluated the impact of the continuation of CDK4/6i beyond first PD in HR+/HER2- MBC using real-world experience. PATIENTS AND METHODS: A single-institution retrospective review of patients with HR+ MBC who received CDK4/6is from 2015 to 2018 and where CDK4/6is were continued beyond first PD. The primary outcome was progression-free survival (PFS) after initial PD on CDK4/6i therapy. RESULTS: Thirty women with HR+/HER2- MBC met eligibility criteria. Patients were identified from a prospective database of patients at the Cleveland Clinic Foundation who were prescribed CDK4/6is. The median age and follow-up duration were 47.5 years and 27 months, respectively. Most patients received palbociclib (PA)/letrozole as initial therapy (67%), followed by PA/fulvestrant (23%), and PA/other aromatase inhibitor (20%), and abemaciclib with either fulvestrant or letrozole (6%). As of January 31, 2019, 25 (83.3%) patients were still alive, and 19 (63%) patients had progressed. The estimated median PFS for continued CDK4/6i use beyond the first PD was 11.8 months (95% confidence interval, 5.34-13.13 months). CONCLUSIONS: Among a small cohort of patients with HR+ MBC in a non-clinical trial setting, continuation of CDK4/6i-endocrine treatment post initial PD was associated with a median PFS of about 12 months. Formal randomized clinical trials evaluating the continuation of CDK4/6is beyond the first PD are currently ongoing and will provide more answers to this important clinical question.

Effects of Ketogenic metabolic therapy on patients with breast cancer: A randomized controlled clinical trial.

BACKGROUND: Ketogenic metabolic therapy (KMT) using ketogenic diets (KD) is emerging as viable alternative or complementary strategy for managing cancer; however, few clinical trials have been reported. The present study aimed to evaluate the effects of a KD in patients with locally advanced and metastatic breast cancer receiving chemotherapy. METHODS: A total of 80 patients undergoing treatment with chemotherapy were randomly assigned to KD or control group for 12 weeks. Concurrent with the admission, midway point, and at 12 weeks, fasting blood samples were collected for evaluation of insulin, IGF-1, CEA, CA15-3, ESR, CRP, IL-10, and TNF-α. Sonography for patients with locally advanced disease and CT or MRI scans for patients with metastatic disease were done on admission and at 12 weeks. At the completion of the chemotherapy, patients with locally advanced disease underwent surgery and stage was recalculated. Also patients with metastases were evaluated for response rate. RESULTS: TNF-α decreased significantly after 12 weeks of treatment (MD: 0.64 [CI 95%: -3.7, 5] P < 0.001), while IL-10 increased (MD: 0.95 [CI 95%: -1,3] P < 0.001) in the intervention compared to the control group. Patients in the KD group had lower adjusted serum insulin compared to the control group (MD:-1.1 [CI 95%: -3,1] p < 0.002). KD lead to a reduction in tumor size in the KD compared to the control (27 vs 6 mm, P = 0.01). Stage decreased significantly in patients with locally advanced disease in the KD group after 12 weeks (P < 0.01). No significant differences in response rate were observed in patients with metastatic disease. CONCLUSIONS: KMT in breast cancer patients might exert beneficial effects through decreasing TNF-α and insulin and increasing IL-10. KD may result in a better response through reductions in tumor size and downstaging in patients with locally advanced disease; however, more studies are needed to elucidate the potential beneficial effects of KD in patients with metastases. TRIAL REGISTRATION: This trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT20171105037259N2. https://www.irct.ir/trial/30755.

Exploring the dietary choices of Chinese women living with breast cancer in Vancouver, Canada.

PURPOSE: To explore how Chinese Canadian patients with breast cancer make dietary choices and to understand their nutritional information needs in order to inform oncology healthcare providers about provision of optimal supportive care for this population. METHODS: Using interpretive description methodology, semi-structured interviews were conducted with first- and second-generation Chinese Canadian women aged 41-73 years living in Vancouver, Canada, who were diagnosed with breast cancer within the last 5 years. A follow-up focus group was held to validate emergent themes. RESULTS: Nineteen women were interviewed; 6 participated in the focus group. Their accounts of dietary experiences following diagnosis focused on three areas: dietary change (including desired and implemented changes that participants believed would benefit their health), facilitators and barriers to dietary change, and information and resource needs. Dietary changes reported included avoiding or consuming greater amounts of certain foods, and taking traditional Chinese medicine (TCM) and natural health products. Barriers to desired dietary change included the interplay between food preferences and family and social life, work-life balance, and cost and availability of specialty foods. Support from family members, however, facilitated participants' consumption of more whole and natural foods after their cancer diagnosis. Participants obtained food and nutrition information from a variety of sources but had difficulty determining the reliability and accuracy of information. They requested timely, credible, culturally-relevant, and easily accessible dietary information. CONCLUSIONS: Oncology healthcare providers would benefit from increased understanding of the dietary practices, including TCM, of Chinese women living with breast cancer. To facilitate communication and improve quality of care, healthcare professionals should provide credible and culturally relevant diet-related information in a variety of forms.

Dietary Changes and Its Impact on Quality of Life among Malay Breast and Gynaecological Cancer Survivors in Malaysia.

OBJECTIVE: Fear of cancer recurrent, side effects of treatment and belief in food taboos encourage cancer survivors to make changes in their dietary practices after diagnosis of cancer. The objective of this study was to determine the impact of dietary changes on quality of life (QoL) among Malay breast and gynaecological cancer survivors. METHODS: Questionnaire of dietary changes was modified from WHEL study and adapted to typical Malay's food intake in Malaysia. A total of 23 items were listed and categorized by types of food and cooking methods.  Four categories of changes "increased", "decreased", "no changes" or "stopped" were used to determine the changes in dietary practices. Score one (+1) is given to positive changes by reference to WCRF/AICR and Malaysia Dietary Guideline healthy eating recommendations. Malay EORTC QLQ-C30 were used to determine the QoL. Sociodemographic, clinical characteristics and anthropometric measurement were also collected. RESULTS: The mean age of the subjects (n=77) was 50.7±7.8 years old with duration of survivorship 4.0±3.1 years. Subjects mean BMI was 27.8±4.9 kg/m2 which indicate subjects were 31.2% overweight and 32.5% obese. The percentage score of positive dietary changes was 34.7±16.4%. Positive dietary changes were increased intake of green leafy vegetable (49.4%), cruciferous vegetable (46.8%) and boiling cooking methods (45.5%). Subjects reduced their intake of red meat (42.9%), sugar (53.2%) and fried cooking method (44.2%). Subjects stopped consuming milk (41.6%), c 2008-5862 heese (33.8%) and sweetened condensed milk (33.8%). With increasing positive dietary changes, there was a significant improvement on emotional function (rs=0.27; p=0.016) and reduced fatigue symptoms (rs=-0.24; p=0.033). CONCLUSION: Positive changes in dietary intake improved emotional function and reduced fatigue symptoms after cancer treatment. By knowing the trend of food changes after cancer treatment, enables the formation of healthy food intervention implemented more effective.

The effect of a ketogenic diet and synergy with rapamycin in a mouse model of breast cancer.

BACKGROUND: The effects of diet in cancer, in general, and breast cancer in particular, are not well understood. Insulin inhibition in ketogenic, high fat diets, modulate downstream signaling molecules and are postulated to have therapeutic benefits. Obesity and diabetes have been associated with higher incidence of breast cancer. Addition of anti-cancer drugs together with diet is also not well studied. METHODS: Two diets, one ketogenic, the other standard mouse chow, were tested in a spontaneous breast cancer model in 34 mice. Subgroups of 3-9 mice were assigned, in which the diet were implemented either with or without added rapamycin, an mTOR inhibitor and potential anti-cancer drug. RESULTS: Blood glucose and insulin concentrations in mice ingesting the ketogenic diet (KD) were significantly lower, whereas beta hydroxybutyrate (BHB) levels were significantly higher, respectively, than in mice on the standard diet (SD). Growth of primary breast tumors and lung metastases were inhibited, and lifespans were longer in the KD mice compared to mice on the SD (p<0.005). Rapamycin improved survival in both mouse diet groups, but when combined with the KD was more effective than when combined with the SD. CONCLUSIONS: The study provides proof of principle that a ketogenic diet a) results in serum insulin reduction and ketosis in a spontaneous breast cancer mouse model; b) can serve as a therapeutic anti-cancer agent; and c) can enhance the effects of rapamycin, an anti-cancer drug, permitting dose reduction for comparable effect. Further, the ketogenic diet in this model produces superior cancer control than standard mouse chow whether with or without added rapamycin.

Short-term effects of a Paleolithic lifestyle intervention in breast cancer patients undergoing radiotherapy: a pilot and feasibility study.

Evolutionary principles are rarely considered in clinical oncology. We here aimed to test the feasibility and effects of a dietary and physical activity intervention based on evolutionary considerations in an oncological setting. A total of 13 breast cancer patients referred to our clinic for curative radiotherapy were recruited for this pilot study. The women were supposed to undertake a "Paleolithic lifestyle" (PL) intervention consisting of a Paleolithic diet and daily outdoor activity of at least 30 min duration while undergoing radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters were assessed before, during, and at the end of radiotherapy. A control group on an unspecified standard diet (SD) was assigned by propensity score matching. A total of eleven patients completed the study. The majority of patients (64%) reported feeling good or very good during the intervention. The intervention group experienced an average decrease of 0.4 kg body weight (p < 0.001) and 0.34 kg (p < 0.001) fat mass per week, but fat-free and skeletal muscle mass were not significantly affected. Vitamin D levels increased slightly from 23.8 (11-37.3) ng/ml to 25.1 (22.6-41.6) ng/ml (p = 0.053). ß-hydroxybutyrate levels were significantly increased and triglycerides and free T3 hormone levels significantly reduced by the PL intervention. This pilot study shows that adoption of a PL intervention during curative radiotherapy of breast cancer patients is feasible and able to reduce fat mass. Daily outdoor activity could eliminate vitamin D deficiency (vitamin D < 20 ng/ml). Future studies are needed to confirm these findings.

Verminoside from Pseudolysimachion rotundum var. subintegrum sensitizes cisplatin-resistant cancer cells and suppresses metastatic growth of human breast cancer.

Breast cancer is one of the most common cancers in women and is associated with a high mortality rate. The majority of deaths resulting from breast cancer are attributable to metastatic growth; in addition, chemoresistance is a major concern in the treatment of patients with breast cancer. However, limited drugs are available for the treatment of metastatic breast cancer. In this study, the chemoadjuvant effects of a methanolic extract from the leaves of Pseudolysimachion rotundum var. subintegrum (NC13) and an active component isolated from the plant, verminoside (Vms), were evaluated. Furthermore, their potent anti-metastatic activities were validated in vitro and in vivo in animal models. The anti-metastatic and chemosensitizing activities of NC13 and Vms on cisplatin treatment were found to be partly mediated by suppression of the epithelial-mesenchymal transition of cancer cells. Collectively, our results implied that NC13 and its bioactive component Vms could be developed as effective chemoadjuvants in combination with conventional therapeutics.

Impact of a ketogenic diet intervention during radiotherapy on body composition: III-final results of the KETOCOMP study for breast cancer patients.

BACKGROUND: Obesity and low muscle mass are associated with worse outcomes of breast cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in breast cancer patients undergoing radiotherapy. METHODS: Patients with non-metastasized breast cancer were allocated to either the KD (N = 32) or the SD (N = 31) during radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters and quality of life were assessed before, during, and at the end of radiotherapy. RESULTS: A total of 29 KD and 30 SD patients completed the study. During radiotherapy, mean and median fasting BHB concentrations in the KD group were 0.72 and 0.49 mmol/l (range 0.06-4.9) which was significantly higher than those in the SD group (p < 2.2 × 10-16). There was a very small and insignificant increase in body weight and fat mass in the SD group, as well as a decrease of fat free mass. In contrast, patients in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses. The KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p < 0.0001). The KD significantly decreased free T3 levels by 0.06 pg/ml/week (p = 6.3 × 10-5). Global quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20). CONCLUSIONS: In breast cancer patients undergoing curative radiotherapy, a KD based on natural foods is feasible. After initial water losses, the KD tends to reduce body weight and fat mass while preserving fat free and skeletal muscle mass. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02516501 , registered on August 06, 2015.

Fasting-mimicking diet and hormone therapy induce breast cancer regression.

Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.

How Dietary Factors Affect DNA Methylation: Lesson from Epidemiological Studies.

Over the past decades, DNA methylation has been proposed as a molecular mechanism underlying the positive or negative effects of diet on human health. Despite the number of studies on this topic is rapidly increasing, the relationship between dietary factors, changes in DNA methylation and health outcomes remains unclear. In this review, we summarize the literature from observational studies (cross-sectional, retrospective, or prospective) which examined the association of dietary factors (nutrients, foods, and dietary patterns) with DNA methylation markers among diseased or healthy people during the lifetime. Next, we discuss the methodological pitfalls by examining strengths and limitations of published studies. Finally, we close with a discussion on future challenges of this field of research, raising the need for large-size prospective studies evaluating the association between diet and DNA methylation in health and diseases for appropriate public health strategies.

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial.

Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18 kg m-2, to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. Trial number: NCT02126449.