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BACKGROUND AND OBJECTIVES: The 9-valent human papillomavirus (9vHPV) vaccine Phase III immunogenicity study in 9- to 15-year-old boys and girls was extended to assess immunogenicity and effectiveness through 10 years after the last vaccine dose (NCT00943722). METHODS: Boys (n = 301) and girls (n = 971) who received three 9vHPV vaccine doses in the base study (day 1, months 2 and 6) enrolled in the extension. Serum was collected through month 126 for antibody assessments by competitive Luminex immunoassay and immunoglobulin G-Luminex immunoassay. For effectiveness analysis starting at age 16 years, genital swabs were collected (to assess HPV DNA by polymerase chain reaction) and external genital examinations conducted every 6 months. Primary analyses were conducted in per-protocol populations. RESULTS: Geometric mean antibody titers peaked around month 7, decreased sharply between months 7 and 12, then gradually through month 126. Seropositivity rates remained ≥81% by competitive Luminex immunoassay and ≥95% by immunoglobin G-Luminex immunoassay at month 126 for each 9vHPV vaccine type. After up to 11.0 (median 10.0) years of follow-up postdose 3, there were no cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or condyloma in males or females. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in males and females were low (54.6 and 52.4 per 10000 person-years, respectively) and within ranges expected in vaccinated cohorts, based on previous human papillomavirus vaccine efficacy trials. CONCLUSIONS: The 9vHPV vaccine demonstrated sustained immunogenicity and effectiveness through â¼10 years post 3 doses of 9vHPV vaccination of boys and girls aged 9 to 15 years.
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OBJECTIVES: The accumulation of tumor-associated macrophages (TAMs) is correlated with poor clinical outcome, but the mechanisms governing their differentiation from circulating monocytes remain unclear in humans. METHODS: Using multicolor flow cytometry, we evaluated TAMs phenotype in 93 breast cancer (BC) patients. Furthermore, monocytes from healthy donors were cultured in the presence of supernatants from dilacerated primary tumors to investigate their differentiation into macrophages (MΦ) in vitro. Additionally, we used transcriptomic analysis to evaluate BC patients' blood monocytes profiles. RESULTS: We observed that high intra-tumor CD163-expressing TAM density is predictive of reduced survival in BC patients. In vitro, M-CSF, TGF-ß and VEGF from primary tumor supernatants skewed the differentiation of healthy donor blood monocytes towards CD163highCD86lowIL-10high M2-like MΦ that strongly suppressed CD4+ T-cell expansion via PD-L1 and IL-10. In addition, blood monocytes from about 40% of BC patients displayed an altered response to in vitro stimulation, being refractory to type-1 MΦ (M1-MΦ) differentiation and secreting higher amounts of immunosuppressive, metastatic-related and angiogenic cytokines. Aside from showing that monocyte transcriptome is significantly altered by the presence of BC, we also demonstrated an overall metabolic de-activation in refractory monocytes of BC patients. In contrast, monocytes from sensitive BC patients undergoing normal M1-MΦ differentiation showed up-regulation of IFN-response genes and had no signs of metabolic alteration. CONCLUSION: Altogether, our results suggest that systemic factors skew BC patient blood monocytes towards a pro-metastatic profile, resulting in the accumulation of further polarised CD163high TAMs resembling type-2 MΦ (M2-MΦ) in the local BC microenvironment. These data indicate that monitoring circulating monocytes in BC patients may provide an indication of early systemic alterations induced by cancer and, thus, be instrumental in the development of improved personalised immunotherapeutic interventions.
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Dendritic cells (DCs) are the most efficient antigen-presenting cells and link the innate immune sensing of the environment to the initiation of adaptive immune responses, which may be directed to either acceptance or elimination of the recognized antigen. In cancer patients, though DCs would be expected to present tumor antigens to T lymphocytes and induce tumor-eliminating responses, this is frequently not the case. The complex tumor microenvironment subverts the immune response, blocks some effector mechanisms, and drives others to support tumor growth. Chronic inflammation in a tumor microenvironment is believed to contribute to the induction of such regulatory/tolerogenic response. Among the various mediators of the modulatory switch in chronic inflammation is the "antidanger signal" chaperone, heat shock protein 27 (Hsp27), that has been described, interestingly, to be associated with cell migration and drug resistance of breast cancer cells. Thus, here, we investigated the expression of Hsp27 during the differentiation of monocyte-derived DCs (Mo-DCs) from healthy donors and breast cancer patients and evaluated their surface phenotype, cytokine secretion pattern, and lymphostimulatory activity. Surface phenotype and lymphocyte proliferation were evaluated by flow cytometry, interferon- (IFN-) γ, and interleukin- (IL-) 10 secretion, by ELISA and Hsp27 expression, by quantitative polymerase chain reaction (qPCR). Mo-DCs from cancer patients presented decreased expression of DC maturation markers, decreased ability to induce allogeneic lymphocyte proliferation, and increased IL-10 secretion. In coculture with breast cancer cell lines, healthy donors' Mo-DCs showed phenotype changes similar to those found in patients' cells. Interestingly, patients' monocytes expressed less GM-CSF and IL-4 receptors than healthy donors' monocytes and Hsp27 expression was significantly higher in patients' Mo-DCs (and in tumor samples). Both phenomena could contribute to the phenotypic bias of breast cancer patients' Mo-DCs and might prove potential targets for the development of new immunotherapeutic approaches for breast cancer.
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Neoplasias da Mama/metabolismo , Células Dendríticas/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Monócitos/metabolismo , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Reação em Cadeia da PolimeraseRESUMO
Cervical cancer, caused by high oncogenic risk Human Papillomavirus (HPV) infection, continues to be a public health problem, mainly in developing countries. Using peptide phage display as a tool to identify potential molecular targets in HPV associated tumors, we identified α-mannosidase, among other enriched sequences. This enzyme is expressed in both tumor and inflammatory compartment of the tumor microenvironment. Several studies in experimental models have shown that its inhibition by swainsonine (SW) led to inhibition of tumor growth and metastasis directly and indirectly, through activation of macrophages and NK cells, promoting anti-tumor activity. Therefore, the aim of this work was to test if swainsonine treatment could modulate anti-tumor immune responses and therefore interfere in HPV associated tumor growth. Validation of our biopanning results showed that cervical tumors, both tumor cells and leukocytes, expressed α-mannosidase. Ex vivo experiments with tumor associated macrophages showed that SW could partially modulate macrophage phenotype, decreasing CCL2 secretion and impairing IL-10 and IL-6 upregulation, which prompted us to proceed to in vivo tests. However, in vivo, SW treatment increased tumor growth. Investigation of the mechanisms leading to this result showed that SW treatment significantly induced the accumulation of myeloid derived suppressor cells in the spleen of tumor bearing mice, which inhibited T cell activation. Our results suggested that SW contributes to cervical cancer progression by favoring proliferation and accumulation of myeloid cells in the spleen, thus exacerbating these tumors systemic effects on the immune system, therefore facilitating tumor growth.
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Proliferação de Células/efeitos dos fármacos , Swainsonina/farmacologia , Neoplasias do Colo do Útero/patologia , alfa-Manosidase/metabolismo , Animais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Quimiocina CCL2/metabolismo , Progressão da Doença , Feminino , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Leucócitos/citologia , Leucócitos/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/citologia , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/metabolismo , Swainsonina/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/virologia , alfa-Manosidase/antagonistas & inibidoresRESUMO
We describe the first case of myasthenia gravis as a possible paraneoplastic manifestation of ovarian cancer preceding its diagnosis.
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DCs orchestrate immune responses contributing to the pattern of response developed. In cancer, DCs may play a dysfunctional role in the induction of CD4(+)CD25(+)Foxp3(+) Tregs, contributing to immune evasion. We show here that Mo-DCs from breast cancer patients show an altered phenotype and induce preferentially Tregs, a phenomenon that occurred regardless of DC maturation stimulus (sCD40L, cytokine cocktail, TNF-α, and LPS). The Mo-DCs of patients induced low proliferation of allogeneic CD3(+)CD25(neg)Foxp3(neg) cells, which after becoming CD25(+), suppressed mitogen-stimulated T cells. Contrastingly, Mo-DCs from healthy donors induced a stronger proliferative response, a low frequency of CD4(+)CD25(+)Foxp3(+) with no suppressive activity. Furthermore, healthy Mo-DCs induced higher levels of IFN-γ, whereas the Mo-DCs of patients induced higher levels of bioactive TGF-ß1 and IL-10 in cocultures with allogeneic T cells. Interestingly, TGF-ß1 blocking with mAb in cocultures was not enough to completely revert the Mo-DCs of patients' bias toward Treg induction. Altogether, these findings should be considered in immunotherapeutic approaches for cancer based on Mo-DCs.
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Neoplasias da Mama/imunologia , Células Dendríticas/imunologia , Ativação Linfocitária/imunologia , Linfócitos T Reguladores/imunologia , Evasão Tumoral/imunologia , Técnicas de Cocultura , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Monócitos/imunologiaRESUMO
BACKGROUND: Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo. METHODS: A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians. RESULTS: Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors. CONCLUSIONS: We found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.
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Hormônios Esteroides Gonadais/sangue , Pós-Menopausa/fisiologia , Adulto , Idoso , Sulfato de Amônio/química , Povo Asiático , Brasil , Fracionamento Químico , Estudos Transversais , Feminino , Humanos , Japão , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
Previous studies showing the presence of antibodies against tumor-associated antigens in healthy individuals suggest that antibody-dependent cell cytotoxicity (ADCC) might play a role in the development of breast cancer. We hypothesized that functional polymorphisms in fragment c gamma receptor (FcgR) genes were associated with breast cancer risk. We conducted hospital-based case-control studies of patients aged 20-74 years with invasive breast cancer, and matched controls from medical checkup examinees in Nagano, Japan and from cancer-free patients in São Paulo, Brazil. A total of 869 pairs (403 Japanese, 80 Japanese Brazilians and 386 non-Japanese Brazilians) were genotyped for two single nucleotide polymorphisms (SNPs): a histidine (H)/arginine (R) polymorphism at position 131 of FcgRIIa (FcgRIIa H131R) and a valine (V)/phenylalanine (F) polymorphism at position 158 of FcgRIIIa (FcgRIIIa F158V). We found no statistically significant association between either of the two SNPs and breast cancer risk regardless of population. In analyses of the three populations combined, adjusted odds ratio (OR) was 0.93 [95% confidence interval (CI) 0.66-1.32] for women with the R/R versus H/H genotype of the FcgRIIa H131R polymorphism and 1.04 (95% CI 0.69-1.57) for the V/V versus F/F genotype of the FcgRIIIa F158V polymorphism. On combination of the two SNPs, compared to women with both the R/R genotype of the FcgRIIa H131R polymorphism and F/F genotype of the FcgRIIIa F158V polymorphism, the adjusted OR for women with both the H/H and V/V genotype was 0.68 (95% CI 0.37-1.27). In conclusion, our findings suggest that ADCC might not play a major role in the etiology of breast cancer.
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Povo Asiático , Neoplasias da Mama/epidemiologia , Receptores de IgG/genética , População Branca , Adulto , Idoso , Brasil/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Japão/etnologia , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores de Risco , Análise de Sequência de DNA , Adulto JovemRESUMO
We tested the hypothesis that polymorphisms in cytochrome P450c17alpha (CYP17), aromatase (CYP19), 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD1) and sex hormone-binding globulin (SHBG) genes may modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based, case-control studies in Nagano, Japan and Sao Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians, and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. Four single nucleotide polymorphisms (SNPs) in CYP17 (rs743572), CYP19 (rs10046), 17beta-HSD1 (rs605059), and SHBG (rs6259) genes were genotyped. We found no association between the 4 SNPs and breast cancer risk. In combination analyses of isoflavone intake and SNPs, an inverse association between intake and risk was limited to women with at least one A allele of the rs605059 polymorphism for all 3 populations, albeit without statistical significance. For the rs6259 polymorphism, the inverse association was limited to postmenopausal Japanese with the GG genotype (odds ratio [OR] for highest vs. lowest tertile = 0.50, 95% confidence interval [CI] = 0.29-0.87; P for trend < 0.01), and to non-Japanese Brazilians with at least one A allele (OR for consumers vs. nonconsumer = 0.21, 95% CI = 0.06-0.77). We found no remarkable difference for the rs743572 and rs10046 polymorphisms. Our findings suggest that polymorphisms in the 17beta-HSD1 and SHBG genes may modify the association between isoflavone intake and breast cancer risk.
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Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Estradiol Desidrogenases/genética , Isoflavonas/administração & dosagem , Polimorfismo de Nucleotídeo Único , Globulina de Ligação a Hormônio Sexual/genética , Esteroide Hidroxilases/genética , Aconitato Hidratase/genética , Adulto , Idoso , Aromatase/genética , Brasil/epidemiologia , Estudos de Casos e Controles , Dieta , Feminino , Frequência do Gene , Estudos de Associação Genética , Hormônios Esteroides Gonadais/metabolismo , Humanos , Japão/epidemiologia , Japão/etnologia , Pessoa de Meia-Idade , Medição de Risco , Esteroide 17-alfa-Hidroxilase/genética , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Several studies have determined that dietary intake of B vitamins may be associated with breast cancer risk as a result of interactions between 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) in the one-carbon metabolism pathway. However, the association between B vitamin intake and breast cancer risk in Brazilian women in particular has not yet been investigated. METHODS: A case-control study was conducted in São Paulo, Brazil, with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate, vitamin B6, and vitamin B12 were derived from a validated Food Frequency Questionnaire (FFQ). Genotyping was completed for MTHFR A1298C and C677T, and MTR A2756G polymorphisms. A logistical regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Neither dietary intake of folate, vitamin B6, or vitamin B12 nor MTHFR polymorphisms were independently associated with breast cancer risk. Analysis stratified by menopausal status showed a significant association between placement in the highest tertile of folate intake and risk of breast cancer in premenopausal women (OR = 2.17, 95% CI: 1.23-3.83; P trend = 0.010). The MTR 2756GG genotype was associated with a higher risk of breast cancer than the 2756AA genotype (OR = 1.99, 95% CI = 1.01-3.92; P trend = 0.801), and statistically significant interactions with regard to risk were observed between the MTHFR A1298C polymorphism and folate (P = 0.024) or vitamin B6 (P = 0.043), and between the MTHFR C677T polymorphism and folate (P = 0.043) or vitamin B12 (P = 0.022). CONCLUSION: MTHFR polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12 had no overall association with breast cancer risk. However, increased risk was observed in total women with the MTR 2756GG genotype and in premenopausal women with high folate intake. These findings, as well as significant interactions between MTHFR polymorphisms and B vitamins, warrant further investigation.
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Neoplasias da Mama/genética , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Vitamina B 12/administração & dosagem , Vitamina B 6/administração & dosagem , Adulto , Idoso , Brasil/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/fisiopatologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
Epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk. Because isoflavones bind estrogen receptors, we hypothesized that polymorphisms in the estrogen receptor genes might modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based case-control studies of patients aged 20-74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from among medical checkup examinees in Nagano, Japan, and from cancer-free patients in São Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires, and provided blood samples. Five single nucleotide polymorphisms in the estrogen receptor alpha (rs9340799, rs1913474, and rs2234693) and beta (rs4986938 and rs1256049) genes were genotyped. We found no consistent association between the five single nucleotide polymorphisms and breast cancer risk among the three populations. In analyses of combinations of isoflavone intake and single nucleotide polymorphisms, an inverse association between intake and risk was limited to women with the GG genotype of the rs4986938 polymorphism for postmenopausal Japanese (odds ratio for highest versus lowest tertile = 0.47; P for trend = 0.01), Japanese Brazilians (odds ratio for highest versus lowest median = 0.31) and non-Japanese Brazilians (odds ratio for consumers versus non-consumers = 0.37) (P for interaction = 0.11, 0.08, and 0.21, respectively). We found no remarkable difference for the other four polymorphisms. Our findings suggest that polymorphisms in the estrogen receptor beta gene may modify the association between isoflavone intake and breast cancer risk.
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Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Isoflavonas/administração & dosagem , Isoflavonas/farmacologia , Polimorfismo Genético/genética , Receptores de Estrogênio/genética , Adulto , Idoso , Alelos , Povo Asiático/genética , Brasil/epidemiologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Inquéritos sobre Dietas , Feminino , Humanos , Japão/epidemiologia , Japão/etnologia , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Fatores de RiscoRESUMO
Although many studies have examined associations between single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2 and CYP1B1 genes and breast cancer risk, no study has examined functional SNPs in the CYP3A5 gene and only a small number of studies have been investigated in Japanese populations. To examine the association between six SNPs, CYP1A1(*)2A, CYP1A1(*)2C, CYP1A2(*)1F, CYP1B1 Arg(48)Gly, CYP1B1 Leu(432)Val and CYP3A5*3 and breast cancer risk, therefore, we conducted hospital-based case-control studies in Nagano, Japan and São Paulo, Brazil including 873 pairs (403 Japanese (JJ), 81 Japanese Brazilians (JB) and 389 non-Japanese Brazilians (NJB)). Although we found no significant association in the three populations combined, subgroup analyses revealed statistically significant associations of CYP1A2*1F in NJB, and CYP1B1 Leu(432)Val and CYP3A5*3 in JJ with breast cancer risk. Compared to women with the AA genotype in CYP1A2*1F, the odds ratio (OR) (95% confidence interval (CI)) for NJB with the CC genotype was 0.54 (0.32-0.90); that for JJ with Leu/Val+Val/Val versus Leu/Leu genotype in CYP1B1 Leu(432)Val was 0.68 (0.48-0.97); and that for JJ with (*)3/(*)1+(*)1/(*)1 versus (*)3/(*)3 genotype in CYP3A5*3 was 1.49 (1.10-2.04). Our findings provide further evidence that genetic polymorphisms related to estrogen metabolism may play a role in the development of breast cancer.
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Indígena Americano ou Nativo do Alasca/genética , Povo Asiático/genética , Neoplasias da Mama/genética , Estrogênios/metabolismo , Predisposição Genética para Doença , Polimorfismo Genético , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Frequência do Gene/genética , Humanos , Japão/etnologia , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Although epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk, little evidence for a dose-response relation is available. We conducted hospital-based case-control studies of patients aged 20-74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from medical checkup examinees in Nagano, Japan and from cancer-free patients in São Paulo, Brazil. A total of 850 pairs (390 Japanese, 81 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. The odds ratio of breast cancer according to isoflavone intake was estimated using a conditional logistic regression model. We found a statistically significant inverse association between isoflavone intake and the risk of breast cancer for Japanese Brazilians and non-Japanese Brazilians. For Japanese, a non-significant inverse association was limited to postmenopausal women. In the three populations combined, breast cancer risk linearly decreased from 'no' to 'moderate' isoflavone intake and thereafter leveled off. Compared to non-consumers, adjusted odds ratios (95% confidence interval) for consumers in increasing quintile intake categories (median intake in each category: 8.7, 23.1, 33.8, 45.7, and 71.3 mg/day) were 0.69 (0.44-1.09), 0.54 (0.31-0.94), 0.45 (0.26-0.77), 0.34 (0.19-0.62), and 0.43 (0.24-0.76), respectively. Overall, we found an inverse association between dietary isoflavone intake and risk of breast cancer. Our finding suggests a risk-reducing rather than risk-enhancing effect of isoflavones on breast cancer within the range achievable from dietary intake alone. In addition, women may benefit from risk reduction if they consume at least moderate amounts of isoflavones.
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Neoplasias da Mama/epidemiologia , Dieta , Isoflavonas/administração & dosagem , Adulto , Idoso , Povo Asiático , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de RiscoRESUMO
Apesar das neoplasias lobulares (NL) terem sido descritas há mais de sessenta anos, ainda suscita dúvidas em relação ao diagnóstico, história natural e tratamento. Avaliamos essas lesões conforme idade, procedimentos que deram origem aos espécimens, classificações, lesões epiteliais proliferativas e carcinomas associados. Revisamos 167 espécimens mamários com diagnóstico de neoplasia lobular, 57,5% com e 42,5% sem lesões associadas. Encontramos frequência de 9,68%. A média etária foi de 52,85 anos. As pacientes com NL associadas com câncer (56,8 anos) apresentaram média etária significativamente maior em relação à ausência desta associação (51,3 anos) (p menor que 0,001). As NL foram classificadas em graus 1,2 e 3, de Tavassoli em respectivamente: 20 (12%), 80 (47,9%) e 67 (40,1%). Segundo os critérios de Page, foram 65 (38,9%) de hiperplasia lobular atípica (HLAT) e 102 (61,1 %) de carcinoma lobular ín sítu. Segundo o tipo histológico 81 (48,5%) eram da forma clássica, 66 (39,5%), híbrida e 20 (12%) pleomórfica. A classificação proposta por Tavassoli refletiu melhor a associação com câncer, (p igual 0,023). A linhagem lobular apresentou maior tendência para NL 3 e ductais com NL 2, assim como o padrão pleomórfico. Os procedimentos restritos ao mesmo quadrante diagnosticaram de 64% dos carcinomas, e 75% das neoplasias intraductais. Os carcinomas associados, 54% eram lobulares. A maior frequência deste diagnóstico foi em material de mamotomia (34,13%). Encontramos 58 casos (34,7%) de neoplasias intra-epiteliais ductais 1B (HDAT). Quando associados com carcinomas, 50% dos casos eram da linhagem ductal, e 18,5% lobular. Observamos 12 casos (7,2%) de neoplasias intra-epiteliais ductais 1C a 3 (CDIS). As alterações com células colunares estavam presentes em 143 casos (85,6%) dos casos...
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Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias da Mama , Lesões Pré-Cancerosas/patologiaAssuntos
Humanos , Feminino , Adulto , Neoplasias de Tecidos Moles , Coxa da Perna , Neoplasias Vulvares , Neoplasias da Mama , Hemangioendotelioma , Evolução FatalRESUMO
Objetivo: relatar série de 15 casos de câncer de mama associado à gravidez e comparar com um grupo controle de pacientes jovens com carcinoma ductal invasivo da mama, avaliando o estadiamento clínico, o comprometimento linfonodal axilar, o grau nuclear, o grau histológico e os receptores hormonais de estrógeno e progesterona. Métodos: foi realizado estudo retrospectivo de 15 casos de pacientes com câncer de mama associado à gravidez, designando como base principal do estudo a avaliação do estadiamento clínico, a época do diagnóstico e o comprometimento axilar. Também, foram analisados a faixa etária, paridade, tipo histológico, tratamento realizado, características histológicas quanto ao grau nuclear e grau histológico, e a presença de receptores hormonais nos tumores diagnosticados. Comparou-se este grupo com um grupo controle de pacientes jovens com câncer de mama. Resultados: verificou-se que 7 pacientes com câncer de mama associado à gravidez (46,7 por cento) encontravam-se com doença localmente avançada (estádio clínico IIIA e IIIB) e 3 pacientes (20 por cento) apresentavam doença disseminada no momento do diagnóstico. As pacientes apresentaram em média 2,4 linfonodos axilares comprometidos, sendo que apenas uma paciente (6,6 por cento) não apresentava comprometimento linfonodal axilar. Com relação à época do diagnóstico, 40 por cento dos cânceres foram diagnosticados durante a lactação, 46,7 por cento durante o terceiro trimestre e 13,3 por cento no segundo trimestre. Comparou-se este grupo de pacientes grávidas com um grupo controle de pacientes, com a mesma média etária, não grávidas, portadoras de carcinoma invasivo de mama analisando o estadiamento clínico, o comprometimento linfonodal axilar, grau nuclear, grau histológico e os receptores hormonais de estrógeno e progesterona. Houve diferença estatisticamente significante (p=0,0022) para o estadiamento clínico e para o comprometimento linfonodal axilar (p=0,0017), não havendo diferença estatisticamente significativa para os demais parâmetros analisados. Conclusão: o câncer de mama associado à gravidez mantém-se como neoplasia de mau prognóstico, não havendo diferença quando se compara com pacientes não grávidas para a mesma média de faixa etária, sendo que o fator determinante na sobrevida é o estádio clínico avançado no momento do diagnóstico
Assuntos
Humanos , Feminino , Gravidez , Adulto , Neoplasias da Mama , Complicações na GravidezRESUMO
A actinomicose mamária é uma doença inflamatória rara, com poucos casos descritos na literatura. Pode ser primária da mama quando resultante de traumas na pele e papila mamária, e, secundária, quando de origem toracopleural. Sua apresentaçäo clínica é variável, devendo ser diferenciada das doenças mais comuns, dentre elas as mastites e também as neoplasias, como o carcinoma inflamatório. Seu diagnóstico é realizado pela cultura da secreçäo, com a identificaçäo das colônias de Actinomyces sp. Seu tratamento é a drenagem, quando indicada, a antibioticoterapia endovenosa e manutençäo oral por tempo prolongado. Os autores relatam caso de abscesso retromamário por Actinomyces sp. em gestante de 12 semanas que apresentava tumoraçäo mamária expansiva na mama esquerda.