Cancer progression is characterized by loss of extracellular matrix (ECM) integrity, which is a precondition for tumor growth and metastasis. In order to elucidate the precise mechanisms of ECM degradation in cancer we used a genetically modified mouse mimicking two distinct human metabolic features associated with carcinogenesis, the lack of endogenous vitamin C synthesis and the production of human Lp(a). Female Lp(a)+; Gulo(-/-) and control wild-type Balb/c mice without these two metabolic features were orthotopically inoculated with 4T1 breast cancer cells (5x105). The transgenic and control mice were divided into 4 different dietary groups in respect to dietary vitamin C intake: i) low ascorbate intake for 6 weeks; ii) high ascorbate intake for 6 weeks; iii) low ascorbate intake for 3 weeks followed by high ascorbate for 3 weeks; iv) high ascorbate intake for 3 weeks followed by low ascorbate for 3 weeks. After 6 weeks, all wild-type mice developed tumors. In contrast, Lp(a)+; Gulo(-/-) mice developed one third less primary tumors (low ascorbate diet) or no primary tumors at all (high ascorbate diet). Significantly, tumors from Lp(a)+; Gulo(-/-) mice immunostained positively for Lp(a) and their size was inversely proportional to Lp(a) serum levels. The results implicate that Lp(a) may play a role in controlling tumor growth and expansion. The most likely mechanism is the competitive inhibition of plasmin-induced ECM degradation due to the homology of Lp(a) components to plasminogen. The confirmation of this pathomechanism could lead to a universal therapeutic target for the prevention and treatment of cancer.

Importance:Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer.

Objective:To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence.

Design, Setting, and Participants:The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians.

Interventions:Participants were randomly allocated to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat).

Main Outcomes and Measures:Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152).

Results:After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.32 (95% CI, 0.13-0.79) for the Mediterranean diet with extra-virgin olive oil group and 0.59 (95% CI, 0.26-1.35) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90).

Conclusions and Relevance:This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra-virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies.

Trial Registration:ISRCTN.org Identifier: ISRCTN35739639.

PURPOSE TO REVIEW:The recent relevant evidence of the effects of the Mediterranean diet (MedDiet) and lifestyle on health (2015 and first months of 2016).

RECENT FINDINGS:Large observational prospective epidemiological studies with adequate control of confounding and two large randomized trials support the benefits of the Mediterranean dietary pattern to increase life expectancy, reduce the risk of major chronic disease, and improve quality of life and well-being. Recently, 19 new studies from large prospective studies showed - with nearly perfect consistency - strong benefits of the MedDiet to reduce the risk of myocardial infarction, stroke, total mortality, heart failure, and disability. Interestingly, two large and well conducted cohorts reported significant cardiovascular benefits after using repeated measurements of diet during a long follow-up period. In addition, Prevención con Dieta Mediterránea, the largest randomized trial with MedDiet, recently reported benefits of this dietary pattern to prevent cognitive decline and breast cancer.

SUMMARY:In the era of evidence-based medicine, the MedDiet represents the gold standard in preventive medicine, probably because of the harmonic combination of many elements with antioxidant and anti-inflammatory properties, which overwhelm any single nutrient or food item. The whole seems more important than the sum of its parts.

Oxidative stress generated by ascorbate-driven menadione redox cycling kills MCF7 cells by a concerted mechanism including glycolysis inhibition, loss of calcium homeostasis, DNA damage and changes in mitogen activated protein kinases (MAPK) activities. Cell death is mediated by necrosis rather than apoptosis or macroautophagy. Neither 3-methyladenine nor Z-VAD affects cytotoxicity by ascorbate/menadione (Asc/Men). BAPTA-AM, by restoring cellular capacity to reduce MTT, underlines the role of calcium in the necrotic process. Oxidative stress-mediated cell death is shown by the opposite effects of N-acetylcysteine and 3-aminotriazole. Moreover, oxidative stress induces DNA damage (protein poly-ADP-ribosylation and gamma-H2AX phosphorylation) and inhibits glycolysis. Asc/Men deactivates extracellular signal-regulated kinase (ERK) while activating p38, suggesting an additional mechanism to kill MCF7 cells. Since ascorbate is taken up by cancer cells and, due to their antioxidant enzyme deficiency, oxidative stress should affect cancer cells to a greater extent than normal cells. This differential sensitivity may have clinical applications.

Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose vitamin C induces pro-oxidant effects and selectively kills cancer cells. However, the anticancer mechanisms of vitamin C are not fully understood. Here, we analyzed metabolic changes induced by vitamin C in MCF7 human breast adenocarcinoma and HT29 human colon cancer cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The metabolomic profiles of both cell lines were dramatically altered after exposure to cytotoxic concentrations of vitamin C. Levels of upstream metabolites in the glycolysis pathway and tricarboxylic acid (TCA) cycle were increased in both cell lines following treatment with vitamin C, while adenosine triphosphate (ATP) levels and adenylate energy charges were decreased concentration-dependently. Treatment with N-acetyl cysteine (NAC) and reduced glutathione (GSH) significantly inhibited vitamin C-induced cytotoxicity in MCF7 cells. NAC also suppressed vitamin C-dependent metabolic changes, and NAD treatment prevented vitamin C-induced cell death. Collectively, our data suggests that vitamin C inhibited energy metabolism through NAD depletion, thereby inducing cancer cell death.

BACKGROUND:Premenopausal women diagnosed with breast cancer are at risk for psychological and behavioral disturbances after cancer treatment. Targeted interventions are needed to address the needs of this vulnerable group.

METHODS:This randomized trial provided the first evaluation of a brief, mindfulness-based intervention for younger breast cancer survivors designed to reduce stress, depression, and inflammatory activity. Women diagnosed with early stage breast cancer at or before age 50 who had completed cancer treatment were randomly assigned to a 6-week Mindful Awareness Practices (MAPS) intervention group (n = 39) or to a wait-list control group (n = 32). Participants completed questionnaires before and after the intervention to assess stress and depressive symptoms (primary outcomes) as well as physical symptoms, cancer-related distress, and positive outcomes. Blood samples were collected to examine genomic and circulating markers of inflammation. Participants also completed questionnaires at a 3-month follow-up assessment.

RESULTS:In linear mixed models, the MAPS intervention led to significant reductions in perceived stress (P = .004) and marginal reductions in depressive symptoms (P = .094), as well as significant reductions in proinflammatory gene expression (P = .009) and inflammatory signaling (P = .001) at postintervention. Improvements in secondary outcomes included reduced fatigue, sleep disturbance, and vasomotor symptoms and increased peace and meaning and positive affect (P< .05 for all). Intervention effects on psychological and behavioral measures were not maintained at the 3-month follow-up assessment, although reductions in cancer-related distress were observed at that assessment.

CONCLUSIONS:A brief, mindfulness-based intervention demonstrated preliminary short-term efficacy in reducing stress, behavioral symptoms, and proinflammatory signaling in younger breast cancer survivors.

BACKGROUND:Premenopausal women diagnosed with breast cancer are at risk for psychological and behavioral disturbances after cancer treatment. Targeted interventions are needed to address the needs of this vulnerable group.

METHODS:This randomized trial provided the first evaluation of a brief, mindfulness-based intervention for younger breast cancer survivors designed to reduce stress, depression, and inflammatory activity. Women diagnosed with early stage breast cancer at or before age 50 who had completed cancer treatment were randomly assigned to a 6-week Mindful Awareness Practices (MAPS) intervention group (n = 39) or to a wait-list control group (n = 32). Participants completed questionnaires before and after the intervention to assess stress and depressive symptoms (primary outcomes) as well as physical symptoms, cancer-related distress, and positive outcomes. Blood samples were collected to examine genomic and circulating markers of inflammation. Participants also completed questionnaires at a 3-month follow-up assessment.

RESULTS:In linear mixed models, the MAPS intervention led to significant reductions in perceived stress (P = .004) and marginal reductions in depressive symptoms (P = .094), as well as significant reductions in proinflammatory gene expression (P = .009) and inflammatory signaling (P = .001) at postintervention. Improvements in secondary outcomes included reduced fatigue, sleep disturbance, and vasomotor symptoms and increased peace and meaning and positive affect (P< .05 for all). Intervention effects on psychological and behavioral measures were not maintained at the 3-month follow-up assessment, although reductions in cancer-related distress were observed at that assessment.

CONCLUSIONS:A brief, mindfulness-based intervention demonstrated preliminary short-term efficacy in reducing stress, behavioral symptoms, and proinflammatory signaling in younger breast cancer survivors.

Women diagnosed with breast cancer received massage therapy or practiced progressive muscle relaxation (PMR) for 30-min sessions 3 times a week for 5 weeks or received standard treatment. The massage therapy and relaxation groups reported less depressed mood, anxiety, and pain immediately after their first and last sessions. By the end of the study, however, only the massage therapy group reported being less depressed and less angry and having more vigor. Dopamine levels, Natural Killer cells, and lymphocytes also increased from the first to the last day of the study for the massage therapy group. These findings highlight the benefit of these complementary therapies, most particularly massage therapy, for women with breast cancer.

In the present study, the fruiting body extracts of Xylaria sp. strain R006 were obtained from hexane, ethyl acetate and methanol. Among them, the ethyl acetate extract exhibited significant antimicrobial activities against bacterial and fungal pathogens. Based on the effective antimicrobial activity, the crude ethyl acetate extract was fractionized by two-step siliga gel column chromatography. All the fractions were tested for antibacterial activity against drug resistant Staphylococcus aureus strains (1-10) and Pseudomonas aeruginosa strains (1-8). The fraction E showed a maximum inhibition zone of 27.9 mm against drug resistant S. aureus strain 3 and 29.4 mm against drug resistant P. aeruginosa strain 4. Minimal inhibitory concentration of fraction E showed potential result against all the drug resistant strains however, the lowest concentration of 75µg/mL-1 was observed against S. aureus strains 1 and 6 and P. aeruginosa strain 3. Further, 60 µg/mL of fraction E had significant cytotoxic activity of 54.9, 55.1 and 54.9% against MDA-MB-231 (breast carcinoma cells), A-549 (lung carcinoma cells) and MCF-7 (breast carcinoma cells) human cancer cell lines, respectively. The spectral data revealed that the fraction E has chromophoric groups in it and had the C = O stretching, C-C = C asymmetric stretch, N-H stretch and C-O stretch as functional groups. The results indicate that the metabolites of fruiting bodies of Xylaria sp. R006 are the potential natural source for the development of new anticancer agents.

Studies have emphasized an antineoplastic effect of the non-psychoactive, phyto-cannabinoid, Cannabidiol (CBD). However, the molecular mechanism underlying its antitumor activity is not fully elucidated. Herein, we have examined the effect of CBD on two different human breast cancer cell lines: the ER-positive, well differentiated, T-47D and the triple negative, poor differentiated, MDA-MB-231 cells. In both cell lines, CBD inhibited cell survival and induced apoptosis in a dose dependent manner as observed by MTT assay, morphological changes, DNA fragmentation and ELISA apoptosis assay. CBD-induced apoptosis was accompanied by down-regulation of mTOR, cyclin D1 and up-regulation and localization of PPARγ protein expression in the nuclei and cytoplasmic of the tested cells. The results suggest that CBD treatment induces an interplay among PPARγ, mTOR and cyclin D1 in favor of apoptosis induction in both ER-positive and triple negative breast cancer cells, proposing CBD as a useful treatment for different breast cancer subtypes.

BACKGROUND:Tumor hypoxia is relevant for tumor growth, metabolism, resistance to chemotherapy and metastasis. We have previously shown that hyperoxia, using hyperbaric oxygen treatment (HBOT), attenuates tumor growth and shifts the phenotype from mesenchymal to epithelial (MET) in the DMBA-induced mammary tumor model. This study describes the effect of HBOT on tumor growth, angiogenesis, chemotherapy efficacy and metastasis in a triple negative MDA-MB-231 breast cancer model, and evaluates tumor growth using a triple positive BT-474 breast cancer model.

MATERIALS AND METHODS:5 x 105 cancer cells were injected s.c. in the groin area of NOD/SCID female mice. The BT-474 group was supplied with Progesterone and Estradiol pellets 2-days prior to tumor cell injection. Mice were divided into controls (1 bar, pO2 = 0.2 bar) or HBOT (2.5 bar, pO2 = 2.5 bar, 90 min, every third day until termination of the experiments). Treatment effects were determined by assessment of tumor growth, proliferation (Ki67-staining), angiogenesis (CD31-staining), metastasis (immunostaining), EMT markers (western blot), stromal components collagen type I, Itgb1 and FSP1 (immunostaining) and chemotherapeutic efficacy (5FU).

RESULTS:HBOT significantly suppressed tumor growth in both the triple positive and negative tumors, and both MDA-MB-231 and BT-474 showed a decrease in proliferation after HBOT. No differences were found in angiogenesis or 5FU efficacy between HBOT and controls. Nevertheless, HBOT significantly reduced both numbers and total area of the metastastatic lesions, as well as reduced expression of N-cadherin, Axl and collagen type I measured in the MDA-MB-231 model. No change in stromal Itgb1 and FSP1 was found in either tumor model.

CONCLUSION:Despite the fact that behavior and prognosis of the triple positive and negative subtypes of cancer are different, the HBOT had a similar suppressive effect on tumor growth, indicating that they share a common oxygen dependent anti-tumor mechanism. Furthermore, HBOT significantly reduced the number and area of metastatic lesions in the triple negative model as well as a significant reduction in the EMT markers N-cadherin, Axl and density of collagen type I.

Pachymic acid (PA), a lanostane-type triterpenoid derived from Poria cocos, possesses demonstrated anti-inflammatory and anti-cancer activities. Nonetheless, the biological properties and mechanism/s of action of PA remain largely undefined. In this study, the activity of PA against breast cancer cell invasion was evaluated. Invasiveness of human-derived MDA-MB-231 and MCF-7 breast carcinoma cells was suppressed by PA at non-lethal concentrations, which was associated with a decrease in matrix metalloproteinase-9 (MMP-9) secretion as a result of PA-mediated down-regulation of MMP-9 mRNA expression. In order to elucidate the underlying anti-invasive mechanism, the effect of PA on transcription factors activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB) was examined using luciferase-based reporter gene assays. PA was found to bring about a reduction in phorbol 12-myristate 13-acetate (PMA)-induced transcriptional activity of NF-kappaB, but not that of AP-1. In accord with the luciferase activity data, western blot analysis showed that PA inhibited NF-kappaB signaling pathway, but did not alter the phosphorylation states of mitogen-activated protein kinases including ERK, JNK, and p38 kinase. The inhibition of PA on NF-kappaB signaling pathway was further attributed to PA-mediated diminution in PMA-induced degradation of inhibitor of kappaBalpha (IkappaBalpha) through preventing phosphorylation of the upstream signal IkappaB kinase (IKK). A decrease in p65 nuclear translocation was achieved, which led to attenuation of NF-kappaB transactivation. Taken together, it was concluded that by targeting NF-kappaB signaling, PA inhibited breast cancer cell invasion through decreasing MMP-9 expression. PA may thus be potentially exploited for use in tumor metastasis intervention.

OBJECTIVE:Photodynamic therapy (PDT) has been used for superficial neoplasms and its usage has been recently extended to deeper lesions. The purpose of this study was to observe whether or not PDT can cure breast cancer in the solid tumor model, and to define the critical point of laser amount for killing the cancer cells.

METHODS:Twenty four BALB/c mouse models with subcutaneous EMT6 mammary carcinomas were prepared. Mice were divided into eight groups depending on the amount of illumination, and the tumor size was between 8 mm and 10 mm. We began by peritoneal infiltration with a photosensitizer 48 hours prior to applying the laser light, and then we applied a non-thermal laser light. The energy was from 350 J/cm(2) to 30 J/cm(2) to the cancer.

RESULTS:Regardless of the tumor size from 8 mm to 10 mm, all mice apparently showed positive results via PDT. We also did not find any recurrence over 90 J/cm(2). In all models, the color of the breast cancer lesions began to vary to dark on 2 days post PDT and the tumor regression began simultaneously. Also, we confirmed the complete regression of the breast cancer 21 days after PDT.

CONCLUSION:We confirmed that PDT may treat breast cancers that are sized less 10 mm in mouse models. The moderate energy to destruct the breast cancer cells may be 90 J/cm(2). Therefore, we can expcect that PDT may be utilized to treat breast cancer, but we need more experience, skills and processing for clinical trials.

The study was conducted to determine the effect of physical activity on DNA methylation and to predict the consequence of this effect concerning gene expression and breast cancer survival. Blood samples, collected from 12 breast cancer patients who participated in a randomized clinical trial of exercise, were examined for exercise-related changes in DNA methylation using a methylation microarray. Tumor samples of 348 breast cancer patients were analyzed with qRT-PCR and qMSP to determine gene expression and methylation identified in the microarray analysis. Cox regression models were developed to predict survival outcomes in association with gene expression and methylation. After 6 months of moderate-intensity aerobic exercise, changes in DNA methylation (P < 5 × 10(-5)) in peripheral blood leukocytes were detected in 43 genes from a panel of 14 495. Based on the list, we analyzed gene expression in association with overall survival in breast tumors and found three genes whose methylation was reduced after exercise were favorably in association with overall survival, i.e., higher expression associated with better survival. Of the three genes, L3MBTL1 was a putative tumor suppressor gene with known function to repress chromatin for transcription, which is activated mainly in germline stem cells. Further analyses of tumor features among patients indicated that high expression of L3MBTL1 was associated with low grade and hormone receptor-positive tumors, as well as low risk of disease recurrence and breast cancer death. In conclusion, the study suggests that increasing physical activity after a breast cancer diagnosis may affect epigeneticregulation of tumor suppressor genes, which have favorable impacts on survival outcomes of breast cancer patients.

BACKGROUND:Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.

OBJECTIVE:This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.

DESIGN:In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed forα-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.

RESULTS:In quintile 5 compared with quintile 1,α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).

CONCLUSION:Our results indicate that higher concentrations of plasmaβ-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.

In spite of the global consumption of mushrooms, only two epidemiological studies demonstrated an inverse correlation between mushroom intake and the risk of cancer. Therefore, in the present study we evaluated whether extracts from edible mushrooms Agaricus bisporus (portabella), Flammulina velutipes (enoki), Lentinula edodes (shiitake) and Pleurotus ostreatus (oyster) affect the growth of breast and colon cancer cells. Here, we identified as the most potent, P. ostreatus (oyster mushroom) which suppressed proliferation of breast cancer (MCF-7, MDA-MB-231) and colon cancer (HT-29, HCT-116) cells, without affecting proliferation of epithelial mammary MCF-10A and normal colon FHC cells. Flow cytometry revealed that the inhibition of cell proliferation by P. ostreatus was associated with the cell cycle arrest at G0/G1 phase in MCF-7 and HT-29 cells. Moreover, P. ostreatus induced the expression of the tumor suppressor p53 and cyclin-dependent kinase inhibitor p21(CIP1/WAF1), whereas inhibited the phosphorylation of retinoblastoma Rb protein in MCF-7 cells. In addition, P. ostreatus also up-regulated expression of p21 and inhibited Rb phosphorylation in HT-29 cells, suggesting that that P. ostreatus suppresses the proliferation of breast and colon cancer cells via p53-dependent as well as p53-independent pathway. In conclusion, our results indicated that the edible oyster mushroom has potential therapeutic/preventive effects on breast and colon cancer.

Breast cancer (BC) is the foremost cause of cancer-related mortality in women worldwide. Polyporus umbellatus is a polysaccharide preparation of the Chinese traditional herb medicine, which has been explored as an inhibitory compounds in suppressing many cancers. And AKT has been known as an essential signaling pathway to regulate cell proliferation and apoptosis via Mdm2/p53 and Caspase-3 signaling pathways respectively. In our study, western blot, RT-PCR, immunochemical assay, immunofluorescence as well as flow cytometry were performed in vitro or in vivo to determine the effects of Polyporus umbellatus on the progression of human laryngeal cancer. First, the breast cancer cell growth, invasion and migration were inhibited, as well as the tumor volume in nude mice was down-regulated for Polyporus umbellatus use. Additionally, our data also showed that Polyporus umbellatus suppressed breast cancer cells proliferation, which was linked with the down-regulation of AKT activation by Polyporus umbellatus treatment. Mdm was inactivated while p53 was stimulated for Polyporus umbellatus administration, displaying inhibitory role in tumor growth. Furthermore, Polyporus umbellatus could up-regulate breast cancer cells in G0/G1 phase during cell cycle, and at the same time reducing cells in S phase. Also, flow cytometry and western blot assays suggested that apoptosis was induced by the administration of Polyporus umbellatus, which enhanced Caspase-3 expressions by AKT-regulated anti-apoptotic and pro-apoptotic signals. In conclusion, our data indicated that Polyporus umbellatus had a potential role in controlling human breast cancer through inhibiting tumor cell proliferation, inducing apoptosis regulated by AKT, which might provide a therapeutic strategy for breast cancer suppression in the future.

Since evidence relating diet to breast cancer risk is not sufficiently consistent to elaborate preventive proposals, the authors examined the association between dietary patterns and breast cancer risk in a large French cohort study. The analyses included 2,381 postmenopausal invasive breast cancer cases diagnosed during a median 9.7-year follow-up period (1993-2005) among 65,374 women from the E3N-EPIC cohort. Scores for dietary patterns were obtained by factor analysis, and breast cancer hazard ratios were estimated by Cox proportional hazards regression for the highest quartile of dietary pattern score versus the lowest. Two dietary patterns were identified: "alcohol/Western" (essentially meat products, French fries, appetizers, rice/pasta, potatoes, pulses, pizza/pies, canned fish, eggs, alcoholic beverages, cakes, mayonnaise, and butter/cream) and "healthy/Mediterranean" (essentially vegetables, fruits, seafood, olive oil, and sunflower oil). The first pattern was positively associated with breast cancer risk (hazard ratio = 1.20, 95% confidence interval (CI): 1.03, 1.38; P = 0.007 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-positive. The "healthy/Mediterranean" pattern was negatively associated with breast cancer risk (hazard ratio = 0.85, 95% CI: 0.75, 0.95; P = 0.003 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-negative. Adherence to a diet comprising mostly fruits, vegetables, fish, and olive/sunflower oil, along with avoidance of Western-type foods, may contribute to a substantial reduction in postmenopausal breast cancer risk.

Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.