Soy and breast cancer: focus on angiogenesis.
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ABSTRACT:
SUBMITTER: Varinska L
PROVIDER: S-EPMC4463727 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
Soy and breast cancer: focus on angiogenesis.
Varinska Lenka L Gal Peter P Mojzisova Gabriela G Mirossay Ladislav L Mojzis Jan J
International journal of molecular sciences 20150522 5
Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action includin ...[more]
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Project description:BackgroundAssociations between soy, dairy intakes and breast cancer risk are inconsistent. No studies exist with large numbers of dairy consumers and soy consumers to assess mutual confounding.MethodsThe study cohort contains 52 795 North American women, initially free of cancer, followed for 7.9 years (29.7% were Black). Dietary intakes were estimated from food frequency questionnaires and, for 1011 calibration study subjects, from six structured 24-h dietary recalls. Incident invasive breast cancers were detected mainly by matching with cancer registries. Analyses used multivariable proportional hazards regression.ResultsThe participants (mean age of 57.1 years) experienced 1057 new breast cancer cases during follow-up. No clear associations were found between soy products and breast cancer, independently of dairy. However, higher intakes of dairy calories and dairy milk were associated with hazard ratios (HRs) of 1.22 [95% confidence interval (CI): 1.05-1.40] and 1.50 (95% CI 1.22-1.84), respectively, comparing 90th to 10th percentiles of intakes. Full fat and reduced fat milks produced similar results. No important associations were noted with cheese and yogurt. Substituting median intakes of dairy milk users by those of soy milk consumers was associated with HR of 0.68 (95% CI: 0.55-0.85). Similar-sized associations were found among pre- and post-menopausal cases, with CIs also excluding the null in estrogen receptor (ER+, ER-), and progesterone receptor (PR+) cancers. Less biased calibrated measurement-error adjusted regressions demonstrated yet stronger, but less precise, HRs and CIs that still excluded the null.ConclusionsHigher intakes of dairy milk were associated with greater risk of breast cancer, when adjusted for soy intake. Current guidelines for dairy milk consumption could be viewed with some caution.
| S-EPMC8453418 | biostudies-literature
Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Genome-wide expression analysis was performed on breast cancer tissue from women following treatment with soy (n=28) or placebo (n=23).
| S-ECPF-GEOD-58792 | biostudies-other
Project description:Angiogenesis has become an important target in the treatment of several solid tumors, including breast cancer. As monotherapy, antiangiogenic agents have demonstrated limited activity in metastatic breast cancer (MBC); therefore, they have generally been developed for use in combination with chemotherapies. Thus far, the experience with antiangiogenic agents for MBC has been mixed. The results from one study assessing addition of the monoclonal antibody bevacizumab to paclitaxel led to approval of bevacizumab for MBC. However, the modest improvement of progression-free survival rates in subsequent MBC studies has led to reappraisal of bevacizumab. Phase III studies have not produced evidence supporting use of the multikinase inhibitor sunitinib alone or in combination with MBC chemotherapy. Experience with sorafenib in a phase IIb program indicates potential when used in select combinations, particularly with capecitabine; however, phase III confirmatory data are needed. Although antiangiogenic therapies combined with chemotherapy have increased progression-free survival rates for patients with MBC, increases in overall survival times have not been observed. Some studies have tried to combine antiangiogenic agents such as bevacizumab and sunitinib or sorafenib, but that approach has been limited because of toxicity concerns. Sequential use of antiangiogenic agents with differing mechanisms of action may be an effective approach. Despite setbacks, angiogenesis will likely remain an important target of treatment for selected patients with MBC.
| S-EPMC3425519 | biostudies-other
Project description:BackgroundSoy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence.MethodsWe searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer.ResultsOf 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects.ConclusionSoy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥ 100 mg) isoflavones can be recommended for breast cancer patients.
| S-EPMC3842968 | biostudies-literature
Project description:The relationship between soy intake (SI) and breast cancer (BC) has been widely investigated with limited information on the significance of hormone receptor status of BC on the association. This study assessed the relationship between SI and BC risk in the context of oestrogen receptor (ER) status of BC. We meta-analyzed data from published studies on SI and BC after a methodical search of EMBASE, PubMed and Cochrane Library through December 2019. Summary estimates with 95% confidence intervals (CI) were presented using a random-effects model. Eighteen (5 cohorts and 13 case-control) studies, were included in this meta-analysis and SI was inversely associated with BC risk [OR (95%) for highest vs. lowest soy food intake = 0.88 (0.84-0.92), P < 0.001, I 2 = 76.1%, Egger's p-value = 0.425] among all women. The inverse relationship was stronger among premenopausal women [OR (95%) = 0.79 (0.71-0.87), P < 0.001, I 2 = 77.3%, Egger's p-value = 0.644]. In addition, SI was inversely associated with BC risk among ER-negative (-) BC women [OR (95%) = 0.71 (0.57-0.90), P = 0.013, I 2 = 72.0%, Egger's p-value = 0.355] and among ER-positive (+) BC women [OR (95%) = 0.87 (0.79-0.96), P = 0.008 I 2 = 74.6%, Egger's p-value = 0.061]. SI appears inversely associated with BC risk, with a stronger inverse association among pre-menopausal and ER-negative BC women.
| S-EPMC7334424 | biostudies-literature
Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.
2014-07-01 | GSE58792 | GEO
Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Genome-wide expression analysis was performed on breast cancer tissue from women following treatment with soy (n=28) or placebo (n=23).
2014-07-01 | E-GEOD-58792 | biostudies-arrayexpress
Project description:Soy isoflavone consumption may protect against breast cancer development. We conducted a phase IIB trial of soy isoflavone supplementation to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high-risk breast. One hundred and twenty-six consented women underwent a random fine-needle aspiration (rFNA); those with 4,000 or more epithelial cells were randomized to a double-blind 6-month intervention of mixed soy isoflavones (PTIG-2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index and atypia. Expression of 28 genes related to proliferation, apoptosis, and estrogenic effect was measured using quantitative reverse transcriptase PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were two-sided. Ninety-eight women were evaluable for Ki-67 labeling index. In 49 treated women, the median Ki-67 labeling index was 1.18 at entry and 1.12 post intervention, whereas in 49 placebo subjects, it was 0.97 and 0.92 (P for between-group change: 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 labeling index increased from 1.71 to 2.18 (P = 0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14 of 28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values showed excellent compliance. A 6-month intervention of mixed soy isoflavones in healthy, high-risk adult Western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women.
| S-EPMC3333836 | biostudies-literature
Project description:Background and aimsAssociations between soy intake and risk of cancer have been evaluated in prospective observational studies with inconsistent results. Whether the potential anticancer effects offered by soy were attributed to soy isoflavones and soy protein still needs to be elucidated. This study aimed to comprehensively quantify the association of soy, soy isoflavones and soy protein intake with risk of cancer incidence and cancer mortality by conducting a meta-analysis of all available studies.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched up to 16 September 2021. Prospective cohort studies that examined the effect of soy, soy isoflavones and soy protein on cancer incidence and cancer mortality were identified. Random-effects models were used to pool the multivariable-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs). The potential dose-response relations were explored by using generalized least-squares trend estimation.ResultsEighty one prospective cohort studies were included in the meta-analysis. A higher intake of soy was significantly associated with a 10% reduced risk of cancer incidence (RR, 0.90; 95% CI, 0.83-0.96). Each additional 25 g/d soy intake decreased the risk of cancer incidence by 4%. Intake of soy isoflavones was inversely associated with risk of cancer incidence (RR, 0.94; 95% CI, 0.89-0.99), whereas no significant association was observed for soy protein. The risk of cancer incidence was reduced by 4% with each 10 mg/d increment of soy isoflavones intake. Similar inverse associations were also found for soy in relation to site-specific cancers, particularly lung cancer (RR, 0.67; 95%CI, 0.52-0.86) and prostate cancer (RR, 0.88; 95%CI, 0.78-0.99). However, high intake of soy, soy isoflavones and soy protein were not associated with cancer mortality.ConclusionsHigher intake of soy and soy isoflavones were inversely associated with risk of cancer incidence, which suggested that the beneficial role of soy against cancer might be primarily attributed to soy isoflavones. These findings support recommendations to include soy as part of a healthy dietary pattern for the prevention of cancer.
| S-EPMC8931954 | biostudies-literature
Project description:Angiogenesis is a critical component of breast cancer development, and identification of imaging-based angiogenesis assays has prognostic and treatment implications. We evaluated the association of semi-quantitative kinetic and radiomic breast cancer features on dynamic contrast-enhanced (DCE)-MRI with microvessel density (MVD), a marker for angiogenesis. Invasive breast cancer kinetic features (initial peak percent enhancement [PE], signal enhancement ratio [SER], functional tumor volume [FTV], and washout fraction [WF]), radiomics features (108 total features reflecting tumor morphology, signal intensity, and texture), and MVD (by histologic CD31 immunostaining) were measured in 27 patients (1/2016-7/2017). Lesions with high MVD levels demonstrated higher peak SER than lesions with low MVD (mean: 1.94 vs. 1.61, area under the receiver operating characteristic curve [AUC] = 0.79, p = 0.009) and higher WF (mean: 50.6% vs. 22.5%, AUC = 0.87, p = 0.001). Several radiomics texture features were also promising for predicting increased MVD (maximum AUC = 0.84, p = 0.002). Our study suggests DCE-MRI can non-invasively assess breast cancer angiogenesis, which could stratify biology and optimize treatments.
| S-EPMC8052427 | biostudies-literature