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1.
Pan Afr Med J ; 40: 23, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733391

RESUMO

Occult breast cancer (OBC) is characterized by metastatic presentation of undetectable breast tumor on imaging exams. OBC is a rare disease (accounting for 0.3% to 1.0% of all breast cancers) that represents a major diagnostic challenge. The aim of this study was to report a case of OBC with primary presentation of multiple cutaneous metastases with subsequent emergence of bone metastasis. A 70-year female patient had multiple cutaneous metastatic lesions in the left cervical region, left breast, left axillary region, left subscapular region, in three chirodactylus of the right hand and three chirodactylus of the left hand. Imaging tests (mammogram, ultrasonography and magnetic resonance imaging of the breast) did not show alterations. Biopsy, histology sections and immunohistochemistry of the left cervical cutaneous lesion were compatible with OBC. After two years of anastrozole treatment (1mg/day), there was regression of all cutaneous lesions and stabilization of bone metastasis. OBC has a better prognosis. It may exhibit spontaneous regression or respond to less aggressive treatment strategies, as described in this case.


Assuntos
Anastrozol/administração & dosagem , Neoplasias da Mama/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Antineoplásicos Hormonais/administração & dosagem , Biópsia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/secundário , Resultado do Tratamento
2.
Molecules ; 26(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34771077

RESUMO

Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/antagonistas & inibidores , Exossomos/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Tamoxifeno/farmacologia , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Exossomos/genética , Exossomos/metabolismo , Feminino , Humanos , Células MCF-7 , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Surg Clin North Am ; 101(6): 1033-1044, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34774266

RESUMO

Breast surgical oncology is a rapidly evolving field with significant advances shaped by practice-changing research. Three areas of ongoing controversy are (1) high rates of contralateral prophylactic mastectomy (CPM) in the United States despite uncertain benefit, (2) indications for and use of neoadjuvant chemotherapy (NACT) and endocrine therapy (NET), and (3) staging and treatment of the axilla, particularly after neoadjuvant systemic therapy. We discuss the patient populations for whom CPM may or may not be beneficial, indications for NACT and NET, and the trend toward de-escalation of locoregional axillary treatment.


Assuntos
Neoplasias da Mama/cirurgia , Antineoplásicos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Humanos , Excisão de Linfonodo , Mamoplastia , Mastectomia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Mastectomia Profilática
4.
BMC Cancer ; 21(1): 1077, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610807

RESUMO

BACKGROUND: The benefits of postoperative chemotherapy in patients with estrogen receptor (ER)-positive breast cancer remain unclear. The use of tumor grade, Ki-67, or ER expression failed to provide an accurate prognosis of the risk of relapse after surgery in patients. This study aimed to evaluate whether a multigene assay Curebest™ 95GC Breast (95GC) can identify the risk of recurrence and provide more insights into the requirements for chemotherapy in patients. METHODS: This single-arm retrospective multicenter joint study included patients with ER-positive, node-negative breast cancer who were treated at five facilities in Japan and had received endocrine therapy alone as adjuvant therapy. The primary lesion specimens obtained during surgery were analyzed using the 95GC breast cancer multigene assay. Based on the 95GC results, patients were classified into low-risk (95GC-L) and high-risk (95GC-H) groups. RESULTS: The 10-year relapse-free survival rates were 88.4 and 59.6% for the 95GC-L and 95GC-H groups, respectively. Histologic grade, Ki-67, and PAM50 exhibited a significant relationship with the 95GC results. The segregation into 95GC-L and 95GC-H groups within established clinical factors can identify subgroups of patients using histologic grade or PAM50 classification with good prognosis without receiving chemotherapy. CONCLUSIONS: Based on the results of our retrospective study, 95GC could be used to evaluate the long-term prognosis of ER-positive, node-negative breast cancer. Even though further prospective validation is necessary, the inclusion of 95GC in clinical practice could help to select optimal treatments for breast cancer patients and identify those who do not benefit from the addition of chemotherapy, thus avoiding unnecessary treatment.


Assuntos
Neoplasias da Mama/genética , Expressão Gênica , Recidiva Local de Neoplasia/genética , Receptores de Estrogênio , Análise Serial de Tecidos/métodos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/classificação , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Japão , Antígeno Ki-67/análise , Linfonodos , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Risco , Taxa de Sobrevida , Fatores de Tempo
5.
Gan To Kagaku Ryoho ; 48(10): 1259-1263, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34657059

RESUMO

BACKGROUND: In step with the aging of the Japanese population, late recurrence of hormone receptor positive (HR+) breast cancer occurring especially beyond 20 years after the initial diagnosis has been recognized as not rare anymore, as it has been occurring at a constant rate lately. The administration of an aromatase inhibitor with a CDK4/6 inhibitor has become the gold standard in Japan for cases of recurring HR+ breast cancer without severe visceral metastasis. CASE: A 73- year-old woman was diagnosed by chance with late recurrence of HR+ breast cancer 21 years after undergoing radical resection followed by adjuvant anastrozole for 5 years for stage Ⅲb right breast cancer. Asymptomatic multiple bone metastases on her ribs and sternum with bilateral lung metastasis and malignant effusion all disappeared while she was on a year- long administration of anastrozole and an optimal dose of abemaciclib(100 mg bid). However, because of the Grade 3 digestive adverse event that occurred at approximately 1 year of treatment, she could only maintain the treatment for up to 13 months. After then, no recurrence has been detectable for 6 months so far. CONCLUSION: CDK4/6 inhibitors, in combination with anastrozole, will play a pivotal role in the initial approach to elderly patients with HR+ late recurrence as a chemotherapy- free strategy.


Assuntos
Neoplasias da Mama , Idoso , Aminopiridinas , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Benzimidazóis , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Hormônios/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Nitrilas/uso terapêutico
6.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638954

RESUMO

Monocarboxylate transporter 2 (MCT2) is a major high-affinity pyruvate transporter encoded by the SLC16A7 gene, and is associated with glucose metabolism and cancer. Changes in the gut microbiota and host immune system are associated with many diseases, including cancer. Using conditionally expressed MCT2 in mice and the TC1 lung carcinoma model, we examined the effects of MCT2 on lung cancer tumor growth and local invasion, while also evaluating potential effects on fecal microbiome, plasma metabolome, and bulk RNA-sequencing of tumor macrophages. Conditional MCT2 mice were generated in our laboratory using MCT2loxP mouse intercrossed with mCre-Tg mouse to generate MCT2loxP/loxP; Cre+ mouse (MCT2 KO). Male MCT2 KO mice (8 weeks old) were treated with tamoxifen (0.18 mg/g BW) KO or vehicle (CO), and then injected with mouse lung carcinoma TC1 cells (10 × 105/mouse) in the left flank. Body weight, tumor size and weight, and local tumor invasion were assessed. Fecal DNA samples were extracted using PowerFecal kits and bacterial 16S rRNA amplicons were also performed. Fecal and plasma samples were used for GC-MS Polar, as well as non-targeted UHPLC-MS/MS, and tumor-associated macrophages (TAMs) were subjected to bulk RNAseq. Tamoxifen-treated MCT2 KO mice showed significantly higher tumor weight and size, as well as evidence of local invasion beyond the capsule compared with the controls. PCoA and hierarchical clustering analyses of the fecal and plasma metabolomics, as well as microbiota, revealed a distinct separation between the two groups. KO TAMs showed distinct metabolic pathways including the Acetyl-coA metabolic process, activation of immune response, b-cell activation and differentiation, cAMP-mediated signaling, glucose and glutamate processes, and T-cell differentiation and response to oxidative stress. Multi-Omic approaches reveal a substantial role for MCT2 in the host response to TC1 lung carcinoma that may involve alterations in the gut and systemic metabolome, along with TAM-related metabolic pathway. These findings provide initial opportunities for potential delineation of oncometabolic immunomodulatory therapeutic approaches.


Assuntos
Carcinogênese/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Transportadores de Ácidos Monocarboxílicos/metabolismo , Carga Tumoral/genética , Animais , Antineoplásicos Hormonais/uso terapêutico , Carcinogênese/genética , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Redes Reguladoras de Genes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Metaboloma/genética , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transportadores de Ácidos Monocarboxílicos/genética , Invasividade Neoplásica/genética , RNA Ribossômico 16S , RNA-Seq , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
7.
Int J Surg Oncol ; 2021: 9947540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567804

RESUMO

Background: Despite the undeniable benefit of tamoxifen therapy for ER-positive breast cancer patients, approximately one-third of those patients either do not respond to tamoxifen or develop resistance. Thus, it is a crucial step to identify novel, reliable, and easily detectable biomarkers indicating resistance to this drug. Objective: The aim of this work is to explore SOX2 and AGR2 biomarker expression in the tumor tissue of ER-positive breast cancer patients in combination with the evaluation of serum AGR2 level of these patients in order to validate these biomarkers as early predictors of tamoxifen resistance. Methods: This study was conducted on 224 ER-positive breast cancer patients. All patients were primarily subjected to serum AGR2 levelling by ELISA and their breast cancer tissue immunostained for SOX2 and AGR2. After 5 years of follow-up, the patients were divided into 3 groups: group 1 was tamoxifen sensitive and groups 2 and 3 were tamoxifen resistant. Time to failure of tamoxifen treatment was considered the time from the beginning of tamoxifen therapy to the time of discovery of breast cancer recurrence or metastases (in months). Results: SOX2 and AGR2 biomarkers expression and serum AGR2 level were significantly higher in groups 2 and 3 in comparison to group 1, while the relationship between Her2 neu expression and Ki67 index in the 3 different groups was statistically nonsignificant. Lower SOX2 and AGR2 expression and low AGR2 serum levels in the studied patients of groups 2 and 3 were significantly associated with longer time-to-failure of tamoxifen treatment. According to the ROC curve, the combined use of studied markers validity was with a sensitivity of 100%, specificity of 96%, PPV 96%, and NPV 100% (p < 0.001; AUC: 0.984). Conclusions: Integrated use of SOX2 and AGR2 biomarkers with serum AGR2 assay holds a promising hope for their future use as predictive markers for early detection of tamoxifen resistance in ER-positive breast cancer patients.


Assuntos
Neoplasias da Mama , Mucoproteínas , Proteínas Oncogênicas , Fatores de Transcrição SOXB1 , Tamoxifeno , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Mucoproteínas/metabolismo , Mucoproteínas/uso terapêutico , Recidiva Local de Neoplasia , Proteínas Oncogênicas/metabolismo , Proteínas Oncogênicas/uso terapêutico , Fatores de Transcrição SOXB1/metabolismo , Tamoxifeno/uso terapêutico
8.
Ann Surg ; 274(4): 654-663, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506321

RESUMO

OBJECTIVE: To identify subgroups of hormone receptor-positive (HR+) breast cancer patients that might not benefit from adding endocrine therapy (ET) to their local treatment. BACKGROUND: De-escalation in breast cancer treatment has included surgery, radiation, and chemotherapy and has often focused on older patient populations. Systemic ET has yet to be de-escalated, though it carries serious side-effects, decreasing quality of life over 5 to 10 years. We hypothesize the 21-gene recurrence score (RS) could identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET. METHODS: The National Cancer Database was used to identify women aged ≥50, with HR+, HER2-negative tumors, ≤3 cm in size, N0 status, and a RS≤25, who underwent breast-conserving surgery in 2010 to 2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). RESULTS: Of the 45,217 patients identified, 80.6% were 50 to 69 years old. 42,632 (94.3%) patients received ET and 2585 (5.7%) did not. The 5-year OS was 96.4% for patients receiving ET and 93.1% for those who did not (P < 0.001). After adjusting for all covariates, patients aged 50 to 69 with RS < 11 showed no statistically significant improvement in OS when adding ET to surgery, with or without radiation (P = 0.40). With RS 11 to 25, there was a significant improvement of OS with ET plus radiation (P < 0.001). CONCLUSIONS: Local treatment only, with de-escalation of long-term ET, for patients aged 50 to 69 with RS < 11, seems not to impact OS and should have an anticipated quality of life improvement. Prospective studies investigating this approach are warranted.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Socioeconômicos , Taxa de Sobrevida , Resultado do Tratamento
9.
Breast Cancer Res Treat ; 190(2): 203-211, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34519905

RESUMO

PURPOSE: Anterior gradient 3 (AGR3) is associated with breast cancer progression, but its relationship with estrogen and tamoxifen resistance in breast cancer is still unclear. This study was designed to investigate the correlation of ARG3 and estrogen as well as the roles of ARG3 in tamoxifen resistance in breast cancer. METHODS: Online database including GEPIA, UALCAN, and TCGA and rVista predictive tool were applied to analyze the expression patterns of AGR3 and its relationship with estrogen receptor 1. AGR3 knockdown and overexpression cell models were constructed. Luciferase reporter assay and ChIP were performed to investigate intermolecular interactions. Western blotting and qPCR were applied to assess targets at mRNA and protein levels, respectively. Cell counting and MTT assay were applied to determine the cell proliferation. RESULTS: An elevation of AGR3 was observed in patients with breast cancer, especially in the patients with estrogen receptor (ER)-positive breast cancer. The TCGA dataset and in vitro data supported that AGR3 was positively correlated to ER. Further results demonstrated that ER protein bound to AGR3 promoter sites. AGR3 expression exhibited a positive correlation to cell viability. Besides, AGR3 promoted tamoxifen resistance in breast cancer. CONCLUSION: AGR3 is associated with estrogen and promotes tamoxifen resistance in breast cancer.


Assuntos
Neoplasias da Mama , Tamoxifeno , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteínas de Transporte , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios/farmacologia , Feminino , Humanos , Proteínas de Neoplasias , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico
10.
Sci Rep ; 11(1): 18511, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531471

RESUMO

Cancer cells acquire drug resistance through the following stages: nonresistant, pre-resistant, and resistant. Although the molecular mechanism of drug resistance is well investigated, the process of drug resistance acquisition remains largely unknown. Here we elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing indicates that tamoxifen-resistant cells can be subgrouped into two, one showing altered gene expression related to metabolic regulation and another showing high expression levels of adhesion-related molecules and histone-modifying enzymes. Pseudotime analysis showed a cell transition trajectory to the two resistant subgroups that stem from a shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted and experimentally validated that inhibition of transition to both resistant subtypes would prevent the appearance of tamoxifen resistance.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Modelos Teóricos , Tamoxifeno/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Tamoxifeno/administração & dosagem
12.
Curr Oncol ; 28(5): 3331-3346, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34590590

RESUMO

Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostatic cancer, but there are many concerns about its systemic side effects, especially due to advanced age and frequent comorbidities in most patients. In patients treated with ADT there are metabolic changes involving the glycaemic control and lipid metabolism, increased thrombotic risk, an increased risk of myocardial infarction, severe arrhythmia and sudden cardiac death. Still, these adverse effects can be also due to the subsequent hypogonadism. Men with heart failure or coronary artery disease have a lower level of serum testosterone than normal men of the same age, and hypogonadism is related to higher cardiovascular mortality. Many clinical studies compared the cardiovascular effects of hypogonadism post orchiectomy or radiotherapy with those of ADT but their results are controversial. However, current data suggest that more intensive treatment of cardiovascular risk factors and closer cardiological follow-up of older patients under ADT might be beneficial. Our paper is a narrative review of the literature data in this field.


Assuntos
Hipogonadismo , Neoplasias da Próstata , Antagonistas de Androgênios/efeitos adversos , Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Humanos , Hipogonadismo/induzido quimicamente , Masculino , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico
13.
Hematology ; 26(1): 775-784, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34565306

RESUMO

OBJECTIVE: Hypoxia is emerging as a key factor in the biology of leukaemia. Here, we want to clarify the impact of hypoxia on the proliferation of T-cell acute lymphoblastic leukaemia (T-ALL) cells and the response to chemotherapy. METHODS: T-ALL cells were cultured under normoxic and hypoxic conditions. MTT assay and trypan blue staining technique was used to detect cell viability and proliferation. In vitro sensitivity to glucocorticoid was assessed by IC50. CDI was used to analyze the combined effects of glucocorticoid and hypoxia. Flow cytometry was performed to detect apoptosis and cell cycle. Western blotting was performed to detect the protein expression associated with hypoxia. RESULTS: Hypoxia of 1% O2 resulted different impact on cell viability and proliferation to different T-ALL cell lines, reduced, unaffected or induced, according to their different metabolic phenotype. All the cell lines showed an induction of key enzymes in glycolysis pathway following hypoxia exposure, although different effector proteins were induced in different cell lines. In GC-sensitive cells, acute hypoxia made no effect on the IC50 of dexamethasone, but chronic hypoxia may improve cell survival and induce GC resistance. However, acute hypoxia induced a higher GC resistance in GC-resistant T-ALL cells and showed an antagonistic effect while combined with high-dose dexamethasone. CONCLUSION: T-ALL cells adapt well to hypoxic environment. Hypoxia may influence leukaemic cell proliferation. More importantly, hypoxia contributes to GC resistance in T-ALL blasts, especially in refractory/relapsed T-ALL.


Assuntos
Antineoplásicos Hormonais/farmacologia , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Hipóxia Tumoral , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Glucose/metabolismo , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Hipóxia Tumoral/efeitos dos fármacos
14.
Anticancer Res ; 41(9): 4535-4542, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475080

RESUMO

BACKGROUND/AIM: Due to the SARS-CoV-2 pandemic, many scientific committees proposed neoadjuvant therapy (NACT) bridging treatment as a novel strategy and indication. The aim of the study was to evaluate the impact of COVID-19 pandemic on breast cancer patients undergoing NACT. PATIENTS AND METHODS: All breast cancer patients referred to two Breast Units during COVID-19-pandemic were enrolled. RESULTS: Out of 814 patients, 43(5.3%) were enrolled in the COVID-19-group and compared with 94 (7.9%) similar Pre-COVID-19 patients. We observed a reduction in the number of patients undergoing NACT, p=0.0019. No difference was reported in terms of clinical presentation, indications, and tumor response. In contrast, a higher number of vascular adverse events was reported (6.9% vs. 0% p=0.029). Immediate breast cancer reconstructions following invasive surgery suffered a significant slowdown (5.9% vs. 47.7%, p=0.019). CONCLUSION: COVID-19 caused a reduction in the number of patients undergoing NACT, with no changes in terms of indications, clinical presentation, and tumor response. Furthermore, there was an increased incidence of vascular events.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , COVID-19/epidemiologia , Mamoplastia/estatística & dados numéricos , Terapia Neoadjuvante/estatística & dados numéricos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , COVID-19/complicações , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Pandemias , Estudos Retrospectivos , Resultado do Tratamento
15.
Breast Cancer Res Treat ; 190(2): 183-188, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34498153

RESUMO

PURPOSE: Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa. METHODS: We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes. RESULTS: A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa. CONCLUSION: Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship.


Assuntos
Neoplasias da Mama , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Gosserrelina/efeitos adversos , Humanos , Preferência do Paciente , Pré-Menopausa , Tamoxifeno/uso terapêutico
16.
Curr Opin Oncol ; 33(6): 538-546, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555836

RESUMO

PURPOSE OF REVIEW: For hormone receptor positive breast cancer, the development of endocrine resistance commonly occurs, presenting as either disease progression in the metastatic setting or recurrence during or following adjuvant endocrine therapy. Various mechanisms of resistance have been described. In order to reduce or overcome endocrine resistance, there has been substantial interest in developing potent and orally bioavailable selective estrogen receptor degraders (SERDs) for metastatic disease and select patients with early-stage estrogen receptor positive breast cancer. RECENT FINDINGS: At least 11 oral SERDs have entered clinical development. We review current studies in both the metastatic and neoadjuvant/adjuvant setting and present the available evidence of benefit and toxicity for these novel agents. Further characterization of changes to tissue-based biomarkers such as estrogen receptor, progesterone receptor and Ki67 expression and blood-based biomarkers such as ctDNA and estrogen receptor 1 mutation may help to refine therapeutic strategies, combinations, and patient selection to identify women who are most likely to benefit from these novel endocrine agents. SUMMARY: Although SERDs have clear therapeutic potential based on nonclinical studies and have demonstrated early signs of activity in phase I and II studies in the metastatic setting, ongoing research is needed to clarify when and in whom these agents may have greatest clinical benefit.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/metabolismo , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Estrogênio/metabolismo
17.
Breast Cancer Res Treat ; 190(3): 451-462, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34570302

RESUMO

PURPOSE: Change in mammographic density has been suggested to be a proxy of tamoxifen response. We investigated the effect of additional adjuvant systemic therapy and CYP2D6 activity on MD change in a cohort of tamoxifen-treated pre- and postmenopausal breast cancer patients. METHODS: Swedish breast cancer patients (n = 699)  operated 2006-2014, genotyped for CYP2D6, having at least three months postoperative tamoxifen treatment, a baseline, and at least one follow-up digital mammogram were included in the study. Other systemic adjuvant treatment included chemotherapy, goserelin, and aromatase inhibitors. Change in MD, dense area, was assessed using the automated STRATUS method. Patients were stratified on baseline characteristics, treatments, and CYP2D6 activity (poor, intermediate, extensive, and ultrarapid). Relative density change was calculated at year 1, 2, and 5 during follow-up in relation to treatments and CYP2D6 activity. RESULTS: Mean relative DA decreased under the follow-up period, with a more pronounced MD reduction in premenopausal patients. No significant effect of chemotherapy, aromatase inhibitors, goserelin, or CYP2D6 activity on DA change was found. DA did not revert to baseline levels after tamoxifen discontinuation. CONCLUSION: Our results indicate that other systemic adjuvant therapy does not further reduce MD in tamoxifen-treated breast cancer patients. We could not confirm the previously suggested association between CYP2D6 activity and MD reduction in a clinical setting with multimodality adjuvant treatment. No rebound effect on MD decline after tamoxifen discontinuation was evident.


Assuntos
Neoplasias da Mama , Tamoxifeno , Antineoplásicos Hormonais/uso terapêutico , Densidade da Mama , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Citocromo P-450 CYP2D6/genética , Feminino , Genótipo , Humanos , Tamoxifeno/uso terapêutico
18.
Medicine (Baltimore) ; 100(32): e26797, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397882

RESUMO

RATIONALE: Polycystic liver disease is a rare disease characterized by the growth of numerous cysts in the liver. The liver function remains well preserved, but liver volumes can grow very large, and some patients ultimately need a liver transplantation. Other treatment options are limited and there is an unmet need for new therapeutic options. PATIENT CONCERNS: We describe a 59-year-old patient with pain in the abdomen, especially when bending forward. Five years ago, she was diagnosed with breast cancer and as an incidental finding a couple of large liver cysts were diagnosed, explaining her abdominal pain. DIAGNOSIS: Polycystic liver disease with several large liver cysts. INTERVENTIONS: The patient was treated with tamoxifen, an estrogen receptor modulator, as treatment for her hormone receptor positive breast cancer. One of the liver cysts was aspirated. OUTCOMES: In the 4.6 years after the start of tamoxifen treatment, 20 mg once daily, the volume of her liver cysts decreased remarkably. There was a reduction of combined cyst volume from 311 mL to 22 mL without percutaneous drainage. LESSONS: Epidemiological as well as experimental evidence supports a pivotal role for estrogens as a driver for growth of polycystic livers. Estrogen antagonism has often been proposed as a therapeutic target, but supporting evidence is lacking in the literature. We hypothesize that the decrease in cyst size in this patient was caused by tamoxifen therapy, suggesting an in vivo antagonistic effect on cystic cholangiocytes. This is an important finding because tamoxifen could be a promising new treatment option for polycystic liver disease.


Assuntos
Cistos/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Tamoxifeno/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Cistos/diagnóstico , Feminino , Seguimentos , Humanos , Hepatopatias/diagnóstico , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
19.
Medicine (Baltimore) ; 100(33): e26949, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414958

RESUMO

BACKGROUND: Ovarian function suppressor (OFS) plus either tamoxifen (TAM) or aromatase inhibitor (AI) could improve the survival outcome for premenopausal hormone receptor-positive (HR+) breast cancer. However, the optimal OFS-based regimen and medication duration remain uncertain. This article aims to systematically evaluate the OFS-based adjuvant endocrine therapy for premenopausal breast cancer. METHODS: We searched several public databases from January 1980 to November 2020. A random model was adopted in this meta-analysis. We used the hazard ratio (HR) with a 95% confidence interval (CI) for the statistical analysis of efficacy. The primary outcome measures included overall survival and disease-free survival. RESULTS: A total of 32 articles with 37,224 cases were included in this network meta-analysis. OFS+TAM improved 5-year disease-free survival (HR -0.09, 95% CI -0.16 to -0.01) and 5-year overall survival (HR -0.18, 95% CI -0.33 to -0.03) compared with TAM monotherapy. For OFS+AI, although the 5-year disease-free survival was improved (HR -0.18, 95% CI -0.29 to -0.08), the 5-year overall survival was not improved (HR -0.13, 95% CI -0.43 to 0.18). In subgroup analysis, both OFS+AI and OFS+TAM showed a protective effect in stage I-III patients compared with stage I-II patients. For the course of therapy, OFS+TAM for 2-years could achieve clinical benefit and the best course of therapy of OFS+AI still waits for further study. CONCLUSIONS: OFS+TAM might be a better option than OFS+AI for premenopausal intensive adjuvant endocrine therapy. Stage III patients are more suitable for the OFS-based therapy. For the medication duration, the 2-years course of OFS+TAM could be effective. This analysis provides helpful information for selecting therapeutic regimen in intensive adjuvant endocrine therapy and identifying the target population.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Metanálise em Rede , Análise de Sobrevida
20.
Cancer Radiother ; 25(6-7): 667-673, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34391651

RESUMO

PURPOSE: While there is no high-level evidence showing superiority of surgery over radiation treatment, radical prostatectomy is the most common treatment option for patients with localized, non-metastatic disease. Nearly 30% of all patients undergoing surgery will develop a biochemical recurrence in 10 years. In fact, more than 30% of contemporary patients treated with RP will harbor aggressive disease characteristics at final pathology. MATERIAL AND MEHODS: We conducted a review of the literature evaluating the timing of radiotherapy and the place of androgen deprivation after prostatectomie totale. RESULTS: Four trials randomizing adjuvant radiotherapy and surveillance found an advantage in biochemical relapse-free survival in favor of immediate irradiation after radical prostatectomy, called adjuvant. However, in these studies, more than 40% of patients in the arm without adjuvant radiotherapy did not relapse at 10 years of follow-up. More recently, the question of the optimal time of this post-operative, adjuvant RT or during biological relapse has arisen through three trials (RADICALS-RT, RAVES, GETUG-AFU 17). These trials did not show a benefit for adjuvant radiotherapy in terms of event-free survival, a PSA-based endpoint, while confirming the toxicities observed during irradiation immediately after surgery. The optimal duration of hormonal therapy when associated with post-prostatectomy radiation therapy remains controversial. CONCLUSION: Early salvage radiotherapy is a new standard of treatment and adjuvant radiotherapy could be reserved for very selected patients. The role of hormone therapy is well defined in salvage situation, but its duration is still being studied.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Humanos , Masculino , Metanálise como Assunto , Recidiva Local de Neoplasia , Cuidados Pós-Operatórios/métodos , Intervalo Livre de Progressão , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Salvação/métodos , Fatores de Tempo
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