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Male breast cancer (MBC) is a rare condition, accounting for approximately 1 % of all breast cancer cases. Nevertheless, the paucity of MBC-specific research has impeded a thorough understanding of MBC. In this study, we aimed to delineate the epidemiological implications of MBC in Brazil and benchmarked it against female breast cancer (FBC). This retrospective study analyzed data from the DATASUS database (2017-2021), which assessed the incidence of breast cancer in both sexes. All statistical analyses were performed using descriptive statistics and inferential methods, with significance set at a 95 % confidence interval. We identified 4,326 (1.7 %) and 233,793 (94.2 %) patients with MBC and FBC, respectively, in Brazil. Despite the general population concentration in the Southeast, MBC cases were more prevalent in the Northeast (p < 0.0004). At breast cancer diagnosis, males were typically older (mean age 59.5 [±10.2] years) than females (mean age 55.7 7 [±9.8] years). MBC was more commonly diagnosed clinically compared with FBC, which was most commonly diagnosed via screening. Surgical diagnostics were twice as likely in males, who also more frequently presented with advanced disease stages (stages III and IV; 72.8 % vs. 59.3 %), leading to a higher rate of mastectomy. Treatment was initiated earlier in males than in females. Although MBC comprises a minority of breast cancer cases, it is more frequently diagnosed at an advanced stage compared with FBC and necessitates aggressive treatment. Our study also underscores the potential benefit of prompt initiation of therapy and need for tailored clinical approaches in patients with MBC.
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BACKGROUND: Neoadjuvant chemotherapy (NAC), traditionally used for locally advanced disease, is now applied for operable disease, particularly to treat aggressive breast cancer (BC). This study aimed to characterize the pathological complete response (pCR) and its relationship with overall survival (OS) and disease-free survival (DFS) among BC patients receiving NAC in a Brazilian public reference center, as well as the association between pCR and BC subtypes. METHODS: A retrospective cohort study used a comprehensive BC database from a Brazilian women's health reference center, including patients diagnosed between 2011 and 2020 who underwent NAC. We collected demographic, cancer-specific, and treatment-related data, analyzing OS and DFS based on pCR status using the semiparametric Kaplan-Meier method, with the date of BC diagnosis as the starting point. RESULTS: The study included 1,601 patients, with an average age of 49 years and a majority presenting stage IIIa disease (35%). Most had invasive nonspecial type (NST) BC (94%), and a significant portion (86.7%) exhibited a Ki-67 index <14. The overall pCR rate was 22.7%, with higher frequencies observed in the triple negative and luminal B subtypes. Patients who achieved pCR had significantly higher survival rates (89% alive vs. 61%, P<0.001) and better DFS (90% vs. 66%, P<0.001), except in the luminal A subtype, where pCR did not correlate with improved OS or DFS. CONCLUSIONS: These updated real-world data (RWD) from BC patients who underwent NAC in Brazil revealed a pCR rate of 22.7% in all cancer subtypes and stages. pCR was not associated with better outcomes in patients with luminal A, contrasting with other subtypes.
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The association between high-density lipoprotein (HDL) cholesterol and breast cancer (BC) remains controversial due to the high complexity of the HDL particle and its functionality. The HDL proteome was determined in newly diagnosed BC classified according to the molecular type [luminal A or B (LA or LB), HER2, and triple-negative (TN)] and clinical stage of the disease. Women (n = 141) aged between 18 and 80 years with BC, treatment-naïve, and healthy women [n = 103; control group (CT)], matched by age and body mass index, were included. Data-independent acquisition (DIA) proteomics was performed in isolated HDL (D = 1.063-1.21 g/mL). Results: Paraoxonase1, carnosine dipeptidase1, immunoglobulin mMu heavy chain constant region (IGHM), apoA-4, and transthyretin were reduced, and serum amyloid A2 and tetranectin were higher in BC compared to CT. In TNBC, apoA-1, apoA-2, apoC-2, and apoC-4 were reduced compared to LA, LB, and HER2, and apoA-4 compared to LA and HER2. ComplementC3, lambda immunoglobulin2/3, serpin3, IGHM, complement9, alpha2 lysine rich-glycoprotein1, and complement4B were higher in TNBC in comparison to all other types; complement factor B and vitamin D-binding protein were in contrast to LA and HER2, and plasminogen compared to LA and LB. In grouped stages III + IV, tetranectin and alpha2-macroglobulin were reduced, and haptoglobin-related protein; lecithin cholesterol acyltransferase, serum amyloid A1, and IGHM were increased compared to stages I + II. Conclusions: A differential proteomic profile of HDL in BC based on tumor molecular classification and the clinical stage of the disease may contribute to a better understanding of the association of HDL with BC pathophysiology, treatment, and outcomes.
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Neoplasias da Mama , Estadiamento de Neoplasias , Proteômica , Humanos , Feminino , Proteômica/métodos , Pessoa de Meia-Idade , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Adulto , Idoso , Lipoproteínas HDL/sangue , Lipoproteínas HDL/metabolismo , Idoso de 80 Anos ou mais , Proteoma/metabolismo , Adolescente , Adulto JovemRESUMO
PURPOSE: Trastuzumab was introduced into the Brazilian public health care service for early breast cancer (BC) in 2012. This study describes the survival outcomes and prognostic factors related to early HER2+ BC treatment in a Brazilian reference cancer center. PATIENTS AND METHODS: This were a retrospective, single-center, observational study of early HER2+ BC patients treated with trastuzumab in the (neo)adjuvant setting between 2012 and 2018 at Hospital Pérola Byington. Demographic, clinical, disease-free survival (DFS) and overall survival (OS) data were evaluated. Multivariate analysis was performed to assess independent prognostic factors. RESULTS: One hundred seventy-six and 353 patients treated in the neoadjuvant and adjuvant setting were included, respectively. The 3- and 5-year OS rates were 79% and 56% for the neoadjuvant group and 97% and 92% for the adjuvant group, respectively. Node positivity at diagnosis predicted poor OS for both groups. In the neoadjuvant group, stage III disease at diagnosis, delayed surgery, and lack of pathological complete response (pCR) predicted poor prognosis. The 3- and 5-year DFS rates were 67% and 46% in the neoadjuvant group and 91% and 86% in the adjuvant group, respectively. Histological grade 2, stage III disease at diagnosis, and lack of pCR predicted poor DFS for the neoadjuvant group. For the adjuvant group, node positivity at diagnosis predicted poor DFS. CONCLUSION: Our results reveal multiple clinical parameters affecting survival outcomes according to the treatment setting. Patients treated with neoadjuvant therapy have a poor prognosis since they present with more advanced disease, indicating the importance of early diagnosis and optimized treatment.
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Neoplasias da Mama , Humanos , Feminino , Trastuzumab , Neoplasias da Mama/patologia , Prognóstico , Estudos Retrospectivos , Brasil/epidemiologia , Receptor ErbB-2/uso terapêutico , Intervalo Livre de Doença , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia AdjuvanteRESUMO
OBJECTIVES: We aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS. METHODS: This was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the KaplanâMeier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS. RESULTS: From 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p < 0,001). Among HER-2+ patients, those who received trastuzumab had a significantly higher pCR rate than those who did not receive trastuzumab (p < 0.0001). Similarly, patients with TNBC who received treatment with platinum-based regimens also showed higher pCR rates (p < 0.0001). OS was grouped according to pCR status, and the OS rate was 88,3% in the pCR group and 58.1% in the non-pCR group (p < 0.0001). The five-year DFS was 92.2% in the pCR group and 64.3% in the non-pCR group (p < 0.0001). CONCLUSION: The pCR rate and its prognostic value varied across BC subtypes. In our study, pCR could be used as a surrogate of favorable clinical outcome, as it was associated with higher OS and DFS rates.
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Neoplasias da Mama , Humanos , Feminino , Adolescente , Adulto , Neoplasias da Mama/patologia , Brasil , Terapia Neoadjuvante , Estudos Retrospectivos , Estudos de Coortes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Trastuzumab/uso terapêutico , Intervalo Livre de DoençaRESUMO
The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.
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Neoplasias da Mama , MicroRNAs , Humanos , Feminino , Neoplasias da Mama/genética , Interleucina-6 , MicroRNAs/genética , Anti-Inflamatórios/farmacologia , Inflamação/genética , Lipoproteínas HDL , Fator de Necrose Tumoral alfaRESUMO
The association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naïve BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.
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Oxisteróis , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Apolipoproteína A-I , Cromatografia Gasosa-Espectrometria de Massas , Lipoproteínas , Colesterol , Triglicerídeos , HDL-ColesterolRESUMO
Introduction: The association between high-density lipoprotein cholesterol (HDLc) with the incidence and progression of breast cancer (BC) is controversial. HDL removes excess cholesterol from cells and acts as an antioxidant and anti-inflammatory. BC is a heterogeneous disease, and its molecular classification is important in the prediction of clinical and therapeutic evolution. Triple-negative breast cancer (TNBC) presents higher malignancy, lower therapeutic response, and survival rate. In the present investigation, the composition and antioxidant activity of isolated HDL was assessed in women with TNBC compared to controls. Methods: Twenty-seven women with a recent diagnosis of TNBC, without prior treatment, and 27 healthy women (control group) paired by age and body mass index (BMI) were included in the study. HDL and low-density lipoprotein (LDL) were isolated from plasma by discontinuous density gradient ultracentrifugation. Plasma lipid profile and HDL composition (total cholesterol, TC; triglycerides, TG; HDLc; phospholipids, PL) were determined by enzymatic colorimetric methods. ApoB and apo A-I were quantified by immunoturbidimetry. The antioxidant activity of HDL was determined by measuring the lag time phase for LDL oxidation and the maximal rate of conjugated dienes formation in LDL incubated with copper sulfate solution. The absorbance (234 nm) was monitored at 37°C, for 4 h, at 3 min intervals. Results: The control group was similar to the TNBC concerning menopausal status, concentrations, and ratios of plasma lipids. The composition of the HDL particle in TC, TG, PL, and apo A-I was also similar between the groups. The ability of HDL to retard LDL oxidation was 22% greater in the TNBC group as compared to the control and positively correlated with apoA-I in HDL. Moreover, the antioxidant activity of HDL was greater in the advanced stages of TNBC (stages III and IV) compared to the control group. The maximum rate of formation of conjugated dienes was similar between groups and the clinical stages of the disease. Discussion: The results highlight the role of HDL as an antioxidant defense in TNBC independently of HDLc plasma levels. The improved antioxidant activity of HDL, reflected by retardation in LDL oxidation, could contribute to limiting oxidative and inflammatory stress in advanced stages of TNBC.
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Introduction: Neoadjuvant chemotherapy is an increasingly frequent option in the treatment of breast cancer. One of the goals of neoadjuvant chemotherapy is to change the indication for a mastectomy to a conservative surgery, and for axillary lymphadenectomy to sentinel lymph node assessment. Methods: This was an observational, cross-sectional, retrospective study that evaluated response to neoadjuvant chemotherapy in breast cancer patients undergoing surgical treatment. Patients were divided into three groups when the surgery indication was changed after neoadjuvant chemotherapy: downgrade, unchanged, upgrade. Results: During the study period, 355 patients were included with a mean age of 55 years. Neoadjuvant chemotherapy promoted a downgrade in 38.7% of patients with indication for mastectomy and an upgrade in 36.8% of patients with indication for conservative surgery; in the total group, the maintenance of indication for surgery was 62,2%. In the axillary approach, lymphadenectomy downgrade was 6.9% and sentinel lymph node biopsy upgrade was 34% with 27% being due to positivity and 7% due to disease progression. Multivariate analysis found a significant difference between clinical staging and change in surgical indication for both breast and axilla (p<0.0001). In the multivariate analysis of pathologic complete response and change of indication for breast and axilla surgery, triple negative and HER-2-positive tumors showed a significant difference (p<0.0001). Conclusions: Neoadjuvant chemotherapy was able to perform a downgrade of breast and axilla surgery in few patients and there was no relationship between the change of indication and pathologic complete response. (AU)
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Humanos , Neoplasias da Mama , Mastectomia Segmentar , Terapia Neoadjuvante , Prognóstico , Cirurgia Geral , MastectomiaRESUMO
OBJECTIVES: Raman spectroscopy has been used to discriminate human breast cancer and its different tumor molecular subtypes (luminal A, luminal B, HER2, and triple-negative) from normal tissue in surgical specimens. MATERIALS AND METHODS: Breast cancer and normal tissue samples from 31 patients were obtained by surgical resection and submitted for histopathology. Before anatomopathological processing, the samples had been submitted to Raman spectroscopy (830 nm, 25 mW excitation laser parameters). In total, 424 Raman spectra were obtained. Principal component analysis (PCA) was used in an exploratory analysis to unveil the compositional differences between the tumors and normal tissues. Discriminant models were developed to distinguish the different cancer subtypes by means of partial least squares (PLS) regression. RESULTS: PCA vectors showed spectral features referred to the biochemical constitution of breast tissues, such as lipids, proteins, amino acids, and carotenoids, where lipids were decreased and proteins were increased in breast tumors. Despite the small spectral differences between the different subtypes of tumor and normal tissues, the discriminant model based on PLS was able to discriminate the spectra of the breast tumors from normal tissues with an accuracy of 97.3%, between luminal and nonluminal subtypes with an accuracy of 89.9%, between nontriple-negative and triple-negative with an accuracy of 94.7%, and each molecular subtype with an accuracy of 73.0%. CONCLUSION: PCA could reveal the compositional difference between tumors and normal tissues, and PLS could discriminate the Raman spectra of breast tissues regarding the molecular subtypes of cancer, being a useful tool for cancer diagnosis.
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Neoplasias da Mama , Análise Espectral Raman , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Análise Discriminante , Feminino , Humanos , Análise dos Mínimos Quadrados , Lipídeos , Análise de Componente Principal , Análise Espectral Raman/métodosRESUMO
PURPOSE: We evaluated the impact of 21-gene test results on treatment decisions for patients with early-stage breast cancer treated under the public health care system in Brazil, Sistema Único de Saúde. METHODS: Eligible patients treated at Hospital Pérola Byington and Santa Casa de Misericórdia de São Paulo in Brazil were required to have the following characteristics: postsurgery with hormone receptor-positive, human epidermal growth factor 2-negative, node-negative and node-positive, and T1/T2 breast cancer and patients with these characteristics were candidates for adjuvant systemic therapy. Treatment recommendations, chemotherapy plus hormonal therapy (CT + HT) or HT alone, were captured before and after 21-gene test results. RESULTS: From August 2018 to April 2019, 179 women were enrolled. The mean age was 58 years (29-86 years), 135 (76%) were postmenopausal, and 58 (32%) had node-positive breast cancer. Most patients (61%) had a tumor > 2 cm, including 7% with tumors > 4 cm. Using Recurrence Score (RS) result cut points on the basis of the TAILORx trial, 40 (22%) had RS 0-10, 91 (51%) had RS 11-25, and 48 (27%) had RS 26-100. Before 21-gene testing, 162 of 179 (91%) patients were recommended for CT. After testing, 117 of 179 patients (65%) had changes in CT recommendation: 112 (63%) who were initially recommended CT received HT alone and five (3%) who were initially recommended HT alone received CT + HT. After 21-gene testing, 99% of physicians reported strong confidence in their treatment recommendations. CONCLUSION: The change in clinical practice at these public hospitals was greater than expected: 66% of initial treatment recommendations were changed to omit CT with 21-gene test results. Clinicopathologic features did not correlate well with 21-gene test results and did not adequately identify those most likely to benefit from CT.
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Neoplasias da Mama , Brasil , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Feminino , Hospitais Públicos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Receptores de Estrogênio/uso terapêuticoRESUMO
Introduction: Breast cancer (BC) centers are increasingly attending "ultra-young" women (UYW) patients (≤ 30 years), who usually present aggressive tumors and face specific problems. Objectives: We aimed to examine a multicentric casuistic view, addressing clinicopathological and molecular characteristics of BC, as well as therapeutic measures and oncological outcomes. Methods: A retrospective multicentric observational study of UYW with infiltrating BC was carried out. The patients were treated between the period from January 1991 to December 2019. Clinical, epidemiological, morphological, molecular, therapeutic and outcomes data were collected from the charts. Results: A total of 293 patients were followed for a average period of 34.5 months. Nulliparity was referred by 204 women (75.5%), of whom 81 (37.1%) were overweight or obese. Positive family history in first-degree relatives was verified in 25 patients (10.1%). Only 30 patients underwent genetic tests, which revealed inherited pathogenic mutations in 12 of them (37.5%). Thirty-two (32) cases were classified as T1 at diagnosis (10.9%), while "De novo" stage IV was found in 29 patients (9.8%). Mastectomy was performed in 175 women (70.2%), quadrantectomy in 46 women (18.4%), and mammary adenectomies in 28 women (11.2%), of which 149 cases were reported after neoadjuvant chemotherapy (56.0%). A total of 111 patients had at least one positive lymph node (47.4%). The rate of patients with estrogen receptor-negative was 32.7% and the rate of patients with Human Epidermal Growth Factor Receptor 2-positive (HER2-positive) was 25%. The frequency of Luminal A neoplasias was 16.6%, Luminal B/HER2- was 35.9%, Luminal B/HER2+ was 15.1%, HER2 overexpressed was 9.3%, and Basal was 22.9%. Taking into account the outcomes, 173 patients were alive without disease (65.7%); 23 patients were alive with any form of recurrence (8.7%); and 67 patients (25.4%) evolved to BC deaths. Conclusions: It was concluded that UYW with BC are commonly diagnosed at advanced stages, present adverse morphological and molecular parameters, and have unfavorable prognosis.
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Breast cancer is the most common malignancy affecting women worldwide. The insulin-like growth factor 1 (IGF-1) gene encodes a protein responsible for a wide variety of physiological processes, including differentiation and cell proliferation. Despite several studies on tumor tissues, no study has evaluated IGF-1 expression in the peripheral blood of women with recurrent breast cancer.In this cross-sectional study, IGF-1 expression in the peripheral blood of 146 women with breast cancer treated approximately 5 years ago was quantified by quantitative reverse transcription polymerase chain. The women were divided into 2 groups: non-recurrence (nâ=â85) and recurrence (nâ=â61). Statistical analysis of the data was performed using ANOVA, Mann-Whitney, and Chi-squared tests (Pâ<â.05).The results showed no significant difference in IGF-1 expression between the non-recurrence and recurrence groups (Pâ=â.988). In the subgroups of patients with lymph node involvement, no statistically significant difference was observed in IGF-1 expression between women with recurrence and those non-recurrence (Pâ=â.113). In patients without lymph node metastases, IGF-1 messenger ribonucleic acid (mRNA) expression levels were significantly higher in the non-recurrence group than in the recurrence group (Pâ=â.019). Furthermore, using the median IGF-1 mRNA expression as the cutoff point, it was obtained a statistically significant difference in tumor histological grade among women with recurrent breast cancer (Pâ=â.042).These data showed significantly higher IGF-1 expression in women without lymph node metastases in the non-recurrence group compared with the recurrence group. In addition, a significant difference was observed in median IGF-1 mRNA expression in relation to tumor histological grade in women with recurrent breast cancer.
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Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Fator de Crescimento Insulin-Like I/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Estudos de Casos e Controles , Diferenciação Celular , Proliferação de Células , Estudos Transversais , Feminino , Expressão Gênica/genética , Humanos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores/métodos , RNA Mensageiro/genéticaRESUMO
BACKGROUND: The CYP19A1 gene, which encodes the enzyme responsible for androgen aromatization into estrogens, may play an important role in breast cancer aggressiveness. However, no study has evaluated CYP19A1 gene expression in the peripheral blood of women with relapsed breast cancer. METHODS: In this cross-sectional study, CYP19A1 gene expression was quantified by RT-PCR in the peripheral blood of 146 women with breast cancer who were first divided into two groups according to the expression of CYP19A1 (low and high); each group had 73 patients. Subsequently, women were divided into two groups: those without recurrence (control, n = 85) and those with recurrence (study, n = 61). Statistical analysis of the data was performed using ANOVA, the Mann-Whitney, Chi-square or Fisher's exact test (p < 0.05). RESULTS: There were no significant differences between the relative expression of CYP19A1 mRNA in the low expression group and the high expression group according to the variables studied. There were no significant differences in CYP19A1 gene expression in the study and control groups (p = 0.8461). In the relapse group, CYP19A1 gene expression was significantly higher in the hybrid luminal subtype than in the triple-negative subtype (p = 0.0321), whereas it was significantly lower in HER2-negative cases than in HER2-positive cases (p < 0.0376). Women with locoregional recurrence showed higher expression than women with distant recurrence (p < 0.0001). CONCLUSIONS: The present study found no significant differences between women with high and low expression of the CYP19A1 gene mRNA or between those in the study group and the control group. However, in women with recurrence, there was increased expression of CYP19A1 mRNA in those who had the luminal hybrid subtype and locoregional relapse and decreased expression in those negative for HER2.
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Aromatase/genética , Neoplasias da Mama/genética , Expressão Gênica , Recidiva Local de Neoplasia/genética , RNA Mensageiro/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aromatase/sangue , Neoplasias da Mama/sangue , Feminino , Genes erbB-2 , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Background: Cancer and fibroadenoma are the most common breast tumors in women of reproductive age. Nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappaB (NF-κB) transcription factor play an important role in the inflammatory process and in cell proliferation. However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age. Results: Light microscopy showed a higher concentration of anti-Nrf2 and anti-NF-κB-stained nuclei in breast cancer than in fibroadenoma. The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.2 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of anti-NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 (mean ± standard deviation) in the control and study groups, respectively (p < 0.0001). Histological grade 3 tumors showed a significantly higher expression of Nrf2 and NF-κB than grade 1 tumors (p < 0.05). Material and methods: This study was approved by the Institutional Review Board of Federal University of Piaui and all patients assigned an inform consent term prior to the study initiation. Nrf2 and NF-κB expression was evaluated by immunohistochemistry in 66 patients, divided into two groups, control (fibroadenoma, n = 36) and study (cancer, n = 30). The data were analyzed using ANOVA test and the statistical significance was established at p < 0.05. Conclusion: Nrf2 and NF-κB expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors.
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ABSTRACT: Patients submitted to oncological fertility preservation with letrozole and gonadotropins seem to present a higher rate of immature oocytes and lower fertilization rates in comparison to infertile patients submitted to IVF cycles with gonadotropins. The aim of this study was to evaluate the influence of letrozole on oocyte morphology in patients with breast cancer submitted to fertility preservation. METHODS: Retrospective analysis performed at a public tertiary hospital in São Paulo, Brazil. The oocytes were retrieved from patients with breast cancer undergoing fertility preservation (n=69), and from infertile women undergoing in vitro fertilization (n=92). We evaluated 750 oocytes obtained from breast cancer patients submitted to ovarian stimulation with letrozole and gonadotropins, and 699 oocytes from patients without breast cancer submitted to ovarian stimulation for in vitro fertilization with gonadotropins only due to male factor infertility. The mature oocytes retrieved were analyzed for the presence of refractile bodies, ooplasm color and regularity, central granulation degree, cortical granules, zona pellucida staining and regularity, perivitelline space, presence of vacuoles or abnormal smooth-surfaced endoplasmic reticle and oocyte retraction. RESULTS: There was a higher incidence of alterations in oocyte morphology in the letrozole group when compared to the control group: increased perivitelline space (p=0.007), irregular zona pellucida (p<0.001), refractile bodies (p<0.001), dark ooplasm (p<0.001), granular ooplasm (p<0.001), irregular ooplasm (p<0.001) and dense central granulation (p<0.001). CONCLUSION: Letrozole is a risk factor for worse oocyte morphology. However, the clinical impact of ovarian stimulation protocol with combined use of gonadotropins and letrozole for fertility preservation remains unclear in this setting. These data underline the importance of establishing the predictive potential of morphological dimorphisms of human oocytes in IVF outcomes.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Infertilidade Feminina/terapia , Letrozol/administração & dosagem , Oócitos/efeitos dos fármacos , Adulto , Forma Celular/efeitos dos fármacos , Criopreservação/métodos , Feminino , Preservação da Fertilidade , Humanos , Infertilidade Feminina/patologia , Recuperação de Oócitos , Oócitos/patologia , Indução da Ovulação/métodos , Estudos RetrospectivosRESUMO
Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Brasil , Lista de Checagem , Terapia Combinada , Diagnóstico Tardio , Países Desenvolvidos , Feminino , Implementação de Plano de Saúde , Humanos , Comunicação Interdisciplinar , Quênia , Romênia , Tempo para o TratamentoRESUMO
PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) has been reported as a side effect of bisphosphonate (BP). The aim of this study was to identify the prevalence of MRONJ in women taking BP for osteoporosis and for metastatic breast cancer and correlate it with risk factors and biochemical markers of bone metabolism. METHODS: Patients taking oral or intravenous BP with osteoporosis (G1; n = 153; median 72.8 years) and with metastatic breast cancer (G2; n = 134; median 58.2 years) had their hospital charts reviewed, were submitted to dental inspection, and answered a health questionnaire. Fasting blood samples were randomly collected from both groups to measure osteocalcin, carboxy-terminal cross-linking telopeptide of type I collagen, intact parathyroid hormone and procollagen type 1 amino-terminal propeptide (P1NP), 25 hydroxyvitamin D (25OHD), creatinine, and total calcium. RESULTS: G1 was older (p = 0.001) and had more cases of diabetes (p = 0.043). P1NP was higher (p = 0.022) and 25OHD lower (p = 0.004) in G2 compared with G1. MRONJ was not found in the G1, whereas 4 cases (3%) were detected in G2. Positive risk factors for MRONJ were number of BP doses and number of visits to the dentist and dental extractions. The biochemical parameters, however, could not identify those who developed MRONJ. CONCLUSIONS: The prevalence of MRONJ was 3% in women with metastatic breast cancer receiving BP. No cases were identified in women receiving oral BP chronically for osteoporosis. P1NP was higher in women with metastatic breast cancer, even during treatment with antiresorptives, but could not differentiate those with MRONJ.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/sangue , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Estudos Transversais , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Hormônio Paratireóideo/sangue , Prevalência , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) 2 and 9 may play an important role in cell proliferation and dissemination of cancer. However, few studies have compared the expression of these proteins between breast cancer and fibroadenoma. MATERIAL AND METHODS: A randomized, double-blind study was carried out in 66 premenopausal women, aged 20-49 years, who had been diagnosed with fibroadenoma or breast cancer. The patients were divided into two groups: Group A, control (fibroadenoma, n=36) and Group B, study (cancer, n=30). Immunohistochemical analysis was performed using tissue samples of fibroadenoma and breast cancer to assess MMP-2 and MMP-9 antigen expression. Cells were considered positive if exhibiting brown cytoplasmic staining. Fisher's exact test was used to compare the percentage of cases with cells expressing MMP-2 and MMP-9 in control and study groups (p < 0.05). RESULTS: Light microscopy showed a higher concentration of cells with positive cytoplasmic staining for MMP-2 and MMP-9 expression in breast cancer than in fibroadenoma. The percentage of cases with cells expressing MMP-2 in the control and study groups was 41.67% and 86.11%, respectively (p < 0.0009), whereas the percentage of cases with cells expressing MMP-9 in groups A and B was 66.67% and 93.33%, respectively (p<0.0138). MMP-2 and MMP-9 positive expression was significantly higher in moderately differentiated tumors compared to well and poorly differentiated tumors, p <0.005 and p<0.001, respectively. CONCLUSIONS: The current study shows that MMP-2 and MMP-9 protein expression was significantly higher in the breast cancer than in the fibroadenoma and also in moderately differentiated breast cancer.
RESUMO
PURPOSE: "Chemobrain" is a medical secondary effect of cancer chemotherapy treatment characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem-solving skills, and motor function. Dopamine (DA) central nervous system neurotransmitters serve an important role in cognition, and changes in DA could potentially explain impaired cognition associated with chemotherapy. Therefore, our objective was to assess in vivo dopaminergic dysfunction in the central nervous system (CNS) of a group of female breast cancer survivors with cognitive impairment following chemotherapy. METHODS: Twenty-eight women reporting chemobrain were recruited for this study and compared to 22 healthy reference women. Striatal dopamine transporter (DAT) binding ratio was determined by 99mTc-TRODAT-1 (a highly selective radiotracer for DAT in the dorsal striatum) single-photon emission computed tomography and a quantitative evaluation was obtained by DatQUANT™ software (GE Healthcare). The DAT binding ratio (BRDAT) in the patient and control groups was compared using the Student's t test, a multivariate analysis of variance (MANOVA) was used to compare age, years of schooling and BRDAT. The relationship between continuous variables, such as cognitive impairment and BRDAT was assessed using Pearson correlation test. RESULTS: There was a difference in BRDAT between the chemobrain patients and control group. Patients had statistically significant (p < 0.05) lower concentrations of the radiopharmaceutical in the striatum. CONCLUSIONS: We identified a significant dopaminergic decrease in all regions of the dorsal striatum within the patients reporting cognitive dysfunction after chemotherapy. Therefore, our results indicate a possible role of dopamine transporter in the physiopathology of chemobrain, even out of the acute phase of symptoms.