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1.
N Engl J Med ; 390(13): 1163-1175, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38598571

RESUMO

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).


Assuntos
Neoplasias da Mama , Excisão de Linfonodo , Linfadenopatia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela , Feminino , Humanos , Axila , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Linfadenopatia/patologia , Linfadenopatia/radioterapia , Linfadenopatia/cirurgia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Terapia Combinada , Seguimentos
2.
Breast Cancer Res Treat ; 204(2): 389-396, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38175449

RESUMO

PURPOSE: Targeted axillary dissection (TAD) for the axillary staging of clinically node-positive (cN +) breast cancer patients converting to clinically node negative post neoadjuvant chemotherapy (NAC), has gained popularity due to its minimal false negative rate and low arm morbidity. The aim of this study is to shed more light on the variation in the clinical practice globally in terms of indications and perceived limitations of TAD. METHODS: A panel of expert breast surgeons constructed a structured questionnaire comprising of 18 questions and asked surgeons worldwide for their opinions and routine practice on TAD. The questionnaire was electronically distributed and answers were collected between May 1st and August 1st 2022. RESULTS: Responses included 137 entries from 36 countries. Of them, 73.7% consider TAD for cN + patients planned to receive NAC. Among them, the greatest number of respondents (45%) perform the procedure for tumours up to T3, whereas 27% regardless of T-stage. The majority (42%) perform TAD on patients with 1-3 positive nodes and only 30% consider TAD when matted nodes are present. HER2 positive and Triple Negative subtypes are more likely to undergo TAD than Luminal A and B (86%, 79.1%, 39.5%, and 62.8%, respectively). Maximum acceptable lymph node burden is median 3 nodes for any subtype with a tendency to accept more positive nodes for Triple Negative. CONCLUSION: This study demonstrates the differences in current practice regarding TAD as well as the fact that the biology of the tumour heavily affects the method of axillary staging.


Assuntos
Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Humanos , Feminino , Biópsia de Linfonodo Sentinela/métodos , Neoplasias da Mama/patologia , Estadiamento de Neoplasias , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Linfonodos/patologia , Terapia Neoadjuvante , Axila/patologia
3.
Breast Cancer Res Treat ; 202(3): 497-504, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37684426

RESUMO

PURPOSE: Currently, various techniques are available to mark and selectively remove initially suspicious axillary lymph nodes (target lymph nodes, TLNs) in breast cancer patients receiving neoadjuvant chemotherapy (NACT). To date, limited data are available on whether the use of magnetic seeds (MS) is suitable for localizing TLNs. This study aimed to investigate the feasibility of MS in patients undergoing target lymph node biopsy (TLNB) or targeted axillary dissection (TAD) after NACT. METHODS: Prospective data from the ongoing multicentric AXSANA study were extracted from selected patients in whom the TLN had been marked with an MS before NACT and who were enrolled from June 2020 to June 2023. The endpoints of the analysis were the detection rate, the rate of lost markers, and the potential impairment on magnetic resonance imaging (MRI) assessment. RESULTS: In 187 patients from 27 study sites in seven countries, MS were placed into the TLN before NACT. In 151 of these, post-NACT surgery had been completed at the time of analysis. In 146 patients (96.0%), a TLN could successfully be detected. In three patients, the seed was removed but no lymphoid tissue was detected on histopathology. The rate of lost markers was 1.2% (2 out of 164 MS). In 15 out of 151 patients (9.9%), MRI assessment was reported to be compromised by MS placement. CONCLUSION: MS show excellent applicability for TLNB/TAD when inserted before NACT with a high DR and a low rate of lost markers. Axillary MS can impair MRI assessment of the breast. TRIAL REGISTRATION NUMBER: NCT04373655 (date of registration May 4, 2020).

4.
Lancet Oncol ; 24(8): e331-e343, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37541279

RESUMO

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Consenso , Estudos Prospectivos , Diagnóstico por Imagem , Metástase Neoplásica
5.
Breast Cancer Res Treat ; 199(2): 293-304, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36879102

RESUMO

PURPOSE: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. METHODS: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. RESULTS: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. CONCLUSIONS: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.


Assuntos
Neoplasias da Mama , Oncologistas , Tumor Filoide , Cirurgiões , Humanos , Feminino , Tumor Filoide/cirurgia , Tumor Filoide/patologia , Estudos Transversais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
6.
Br J Surg ; 109(9): 857-863, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35766257

RESUMO

BACKGROUND: There is no consensus on axillary management after neoadjuvant therapy (NAT) in patients with clinically node-positive (cN+) breast cancer. To investigate current clinical practice, an international survey was conducted among breast surgeons and radiation oncologists. The aim of the first part of the survey was to provide a snapshot of international discrepancies regarding axillary surgery in this context. METHODS: The European Breast Cancer Research Association of Surgical Trialists (EUBREAST) developed a web-based survey containing 39 questions describing clinical scenarios in the setting of axillary management in patients with cN1 disease converting to ycN0 after NAT. The survey was then distributed to breast surgeons and radiation oncologists via 14 breast cancer societies between April and October 2021. RESULTS: Responses from 349 physicians in 45 countries were recorded. The most common post-NAT axillary surgery in patients with cN1 disease converting to ycN0 was targeted axillary dissection (54.2 per cent), followed by sentinel lymph node biopsy (SLNB) alone (20.9 per cent), level 1-2 axillary lymph node dissection (ALND) (18.4 per cent), level 1-3 ALND (4 per cent), and targeted lymph node biopsy (2.5 per cent). For SLNB alone, dual tracers were most commonly used (62.3 per cent). Management varied widely in patients with ambiguous axillary status before initiation of treatment or a residual metastatic burden in the axilla after NAT. In patients with ycN+ tumours, ALND was the preferred surgical approach for 66.8 per cent of respondents. CONCLUSION: These results highlight the wide heterogeneity in surgical approaches to the axilla after NAT. To standardize the guidelines, further data from clinical research are urgently needed, which underlines the importance of the ongoing AXSANA (EUBREAST-3) study.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Terapia Neoadjuvante/métodos , Biópsia de Linfonodo Sentinela/métodos
7.
Breast ; 63: 123-139, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35366506

RESUMO

AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.


Assuntos
Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/métodos , Mamilos , Estudos Prospectivos
8.
Breast Care (Basel) ; 16(5): 532-538, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34720813

RESUMO

INTRODUCTION: Targeted axillary dissection (TAD) has been proposed as an alternative method for the staging of patients with node-positive breast cancer who undergo neoadjuvant chemotherapy. However, not much is known yet about the false-negative rate (FNR) of the method and the subsequent risk of underestimation of residual axillary disease. METHODS: This study reviews published articles with calculations of false negativity of TAD and potential factors that may influence it. RESULTS: The FNR of TAD is usually reported as being <10%, but this calculation is usually based on small study populations. Lower FNR is a common finding along with lower N status, while not enough data are available yet for greater axillary involvement. When a marked node is revealed to be a sentinel lymph node (SLN) at surgery after neoadjuvant chemotherapy (NAC), this seems to be another factor that contributes to reliable TAD. With regard to the methods used to mark the positive node before chemotherapy and retrieval at surgery, there is no clear advantage of one over the other. The availability of relevant resources, the costs, and local legislation must all be taken into account for the selection of the optimal strategy. CONCLUSION: Although still in its early days, the FNR of TAD can be low, at least in patients with relatively little axillary involvement and when the marked node is the SLN. All reported methods of lymph node marking seem reliable.

9.
Ann Plast Surg ; 87(1): 16-23, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34133364

RESUMO

ABSTRACT: Mastectomy and immediate reconstruction may be challenging in patients with large breasts, especially when significant ptosis is also present. Skin-reducing mastectomy (SRM) is usually indicated in these cases, although with increased morbidity. The aims of the study were to introduce 2 modifications of the classic technique and to incorporate them in the management algorithm to improve the outcomes.Twenty patients fulfilling the criteria for SRM underwent mastectomy and reconstruction either with the "classic SRM" (8 patients) or with 1 of the 2 modifications described here: modification A "vertical limb bridging" (for patients with very large breasts, 2 patients) and modification B "dual coverage" (for patients with moderate breasts, 10 patients). All reconstructions were performed using a slow progressive expansion of the implant. Herein, we describe the techniques along with the proposed indications for each one of them.There was no reconstruction failure, and all patients were satisfied with the final results. There were 2 cases with T junction, lateral skin flap partial ischemia managed with delayed revision of the wound on the fifth postoperative day to allow less skin excision. One patient (smoker) developed severe lower pole cellulitis, which was managed conservatively. Finally, 1 patient who underwent radiotherapy developed a late infected seroma, which was managed successfully with drainage and antibiotics. Overall, there was good lower pole projection even with the dual-coverage modification.Skin-reducing mastectomy can be tailored according to individual patient anatomy, and the high reported complication rate associated with this technique can be minimized using certain surgical modifications, tissue expanders with progressive inflation, and good patient selection.


Assuntos
Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Hipertrofia/cirurgia , Mastectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos
10.
Cancers (Basel) ; 13(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805367

RESUMO

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

11.
J Gynecol Obstet Hum Reprod ; 50(8): 101991, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33238218

RESUMO

INTRODUCTION: Sentinel node (SN) assessment via frozen section (FS) has declined since the publication of Z0011 which modified the management of a specific group of patients with positive SN. The risk of misleading the surgeons to a preventable ALND and the cost are among the main factors for that. The aim of our study is to assess the value of FS in the post Z0011. MATERIAL AND METHODS: 244 patients out of 434 were eligible for an upfront SLNB. Based on the final histology and the clinical data we selected the eligible for breast conserving surgery patients (55.4%). 78 patients had positive SN and 26 of them fulfilled the criteria of Z0011. We assessed the false negative findings, the impact on the management and the indications and value of FS in the post Z0011 era. RESULTS: Overall, there were 12 FN cases out of which 7 were macrometastases (8.97%). Only in one case there were > 2 positive LN and 3 patients needed mastectomy. The remaining cases fulfilled the criteria of Z0011 and needed no further surgery hence in 96.1% of the cases the axillary status was correctly assessed via FS and the reoperation rate was 1.2%. On the contrary, if FS was not used, at least 21.3% of the patents would have needed reoperation based on the today's guidelines. DISCUSSION: We believe FS is still valuable and may spare a significant percentage of patients from a second operation (SNB) without leading to axillary overtreatment if used wisely.


Assuntos
Cuidados Intraoperatórios/normas , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Feminino , Secções Congeladas/métodos , Secções Congeladas/estatística & dados numéricos , Grécia , Humanos , Cuidados Intraoperatórios/métodos , Cuidados Intraoperatórios/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Linfonodo Sentinela/fisiopatologia
12.
BMC Surg ; 20(1): 210, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957940

RESUMO

BACKGROUND: The continuously increasing survivorship of female breast cancer makes the monitoring and improvement of patients' quality of life ever so important. While globally there is a growing body of research on health-related quality of life 1 year after surgical treatment for non-metastatic breast cancer, up-to-date information regarding Greek patients is scarce. OBJECTIVE: To measure the level of QoL of non-metastatic BC survivors in Greece 1 year after surgery. METHODS: A sample of 200 female breast cancer survivors aged 18 to 75, who followed up as outpatients in five public hospitals were included in this cross-sectional study. All recruited patients agreed to participate in the study (100% response rate). Quality of life data were collected through the EORTC QLQ-C30 as well as BR23 questionnaires. RESULTS: Cronbach's alpha for all scales of the two questionnaires was from 0.551 to 0.936 indicating very good reliability. According to the Multiple Linear Regression, older patients showed a lower future perspective (p = .031), with those living in rural areas, which was associated with more financial difficulties (p = .001). Women with tertiary education and those who had been hospitalized in a university hospital recorded better on global health status (p = .003 and .000 respectively). Patients who underwent chemotherapy reported better scores in the emotional function sub-scale (p = .025). Women with reconstruction and at least one complication appeared to have significantly better scores in future perspective and social function (p = .005, .002 respectively). CONCLUSIONS: Breast cancer survivors were found to have an overall good quality of life, functioning/symptoms scores and were satisfied with the provided care.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Qualidade de Vida , Mulheres , Adolescente , Adulto , Afeto , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Estudos Transversais , Feminino , Grécia , Humanos , Mastectomia , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
15.
Breast Care (Basel) ; 14(1): 48-52, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31019443

RESUMO

BACKGROUND: Delayed breast cellulitis (DBC) is a relatively rare complication following breast-conserving surgery. It is often challenging to distinguish DBC from other clinical conditions such as postoperative infection, inflammatory reaction following radiation, and recurrent inflammatory carcinoma. The definition of DBC, diagnostic approach, and treatment are not well established in the literature. METHODS: We performed a literature search with the keywords 'Delayed breast cellulitis' and 'Breast conservation therapy cellulitis', without limitations to the dates or the article types, in the PubMed database. Information about the number of cases with DBC, the age of the patients, the interval between the onset of symptoms and the time of surgery or radiotherapy, and the type and outcome of DBC treatment were reviewed and tabulated. RESULTS: We identified only 5 papers that were absolutely related to our subject, reflecting the fact that 'delayed breast cellulitis' is a fairly unknown term and the condition is rather underreported. Although most agree that DBC is primarily an aseptic inflammatory process, bacterial growth may contribute to its development or recurrence. Obesity, breast size, location of the breast tumor, removal of the axillary lymph nodes, and connective tissue disorders are considered as risk factors. There is no clear evidence on how DBC should be best managed. Antibiotic treatment is controversial, and many authors suggest anti-inflammatory agents or sole observation. Prevention of lymph stasis and its consequences with massage and skin care may be helpful. Despite the fact that malignancy is rare, in cases where the condition persists for more than 4 months, a core biopsy should be performed to rule out recurrent or second primary carcinoma. CONCLUSION: The correct diagnostic approach is essential as it provides patients with reassurance, minimizes anxiety, and prevents unnecessary medical investigations, treatments, and costs.

16.
J Cancer Res Clin Oncol ; 145(5): 1221-1233, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30805773

RESUMO

PURPOSE: Androgen receptor (AR) is playing an important role in the progression of a subset of TNBC. We evaluated the impact of ERß expression along with anti-AR drugs in AR-positive TNBC. METHODS: ERß expression was examined in AR-positive TNBC cell line using MTT assay, scratch and Annexin V-FITC assay in the presence or absence of anti-androgens. Protein levels of involved molecules were assessed using Western blot. Receptors' localization was detected by immunofluorescence and their physical association was examined using proximity ligation assay (PLA), which enables the visualization of interacting proteins in fixed cells and tissues. RESULTS: Transient transfection of ERß in MDA-MB 453 AR-positive TNBC cell line significantly inhibited cell proliferation, metastatic potential and induced apoptosis. ERß expression reversed the aggravating role of AR in both indirect and direct ways. Indirectly, ERß decreased AR activation through the inhibition of PI3K/AKT signaling pathway. Directly, ERß formed heterodimers with AR in MDA-MB 453 cells and in human tissue samples impeding AR from forming homodimers. Enzalutamide is a more potent anti-androgen in AR + TNBC compared to bicalutamide. ERß expression increased the sensitivity of MDA-MB 453 cells to anti-androgens and especially to enzalutamide. The administration of enzalutamide enhanced AR:ERß heterodimers formation increasing the anti-tumor capacity of ERß. CONCLUSIONS: Collectively, our results provide evidence for a novel mechanism by which ERß exerts oncosuppressive effect in AR-positive TBNC through direct and indirect interactions with AR. Moreover, ERß expression may identify a new subset of TNBC that would respond more favorable to anti-androgens.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Receptor beta de Estrogênio/metabolismo , Feniltioidantoína/análogos & derivados , Receptores Androgênicos/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Apoptose , Benzamidas , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células , Receptor beta de Estrogênio/química , Receptor beta de Estrogênio/genética , Expressão Gênica , Humanos , Imuno-Histoquímica , Nitrilas , Feniltioidantoína/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Ligação Proteica , Multimerização Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Androgênicos/química , Receptores Androgênicos/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
17.
Clin Drug Investig ; 38(7): 639-648, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29744672

RESUMO

BACKGROUND: In the era of personalized therapy, targeted treatment in specific patient populations is mandated. OBJECTIVE: We evaluated the efficacy and safety of neoadjuvant treatment on locally advanced breast cancer (LABC) with a monoclonal agent against vascular endothelial growth factor (VEGF), bevacizumab plus chemotherapy combination of liposomal doxorubicin, cyclophosphamide and paclitaxel (PLAC-B). METHODS: Patients enrolled were at premenopausal status and characterized by human epidermal growth factor receptor 2 (HER2)-negative, hormone-receptor positive (estrogen receptor/progesterone receptor-positive [ER/PR+]) or triple-negative (TNBC), LABC (T > 3 cm), with high-grade ductal carcinoma. Patients had to have a measurable disease and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, with adequate hematologic, renal, and hepatic function. Patients received intravenous liposomal doxorubicin 30 mg/m2, cyclophosphamide 600 mg/m2, paclitaxel 120 mg/m2, and bevacizumab 8 mg/kg on day 1 of 15-day cycles for four cycles (four administrations as neoadjuvant treatment). The primary endpoint was complete clinical (cCR) and pathologic (pCR) response rates, while secondary endpoints included safety, breast-conserving surgery (BCS) conversion rate, and disease-free survival (DFS). RESULTS: Sixty-two women were enrolled; 20 were ER/PR+ and 42 had TNBC. All underwent surgery, six received mastectomy, and 56 (90.3%) received BCS, with an equal conversion rate from initial indication for mastectomy. cCR was 25.8%. pCR in the breast and axilla occurred in 24 patients (38.7%). pCR was 42.9% for TNBC and 30% for ER/PR+. Hematologic adverse events (AEs) included neutropenia (74.2% total; 22.6% grade 3 [G3]) and febrile neutropenia (6.5% G3); non-hematologic G3 AEs included nausea (6.5%), mucositis (9.7%), and infection (3.2%), all of which were managed without negative sequelae. Over a 3-year follow-up, all patients were alive and DFS was 87.1%. CONCLUSION: PLAC-B as neoadjuvant treatment of this subpopulation with TNBC and ER/PR+ patients is effective and safe. Further studies are necessitated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Pré-Menopausa/efeitos dos fármacos , Receptor ErbB-2 , Adulto , Bevacizumab/administração & dosagem , Neoplasias da Mama/diagnóstico por imagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Paclitaxel/administração & dosagem , Polietilenoglicóis/administração & dosagem , Resultado do Tratamento
18.
J BUON ; 23(1): 1-6, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29552751

RESUMO

PURPOSE: The purpose of the present article was to investigate the health related quality of life (QoL) of young women with breast cancer. METHODS: For the purposes of this article, we reviewed the literature via the electronic databases Pubmed, Scopus and Google Scholar. Key words used were breast cancer, young women, health related quality of life, and quality of life. RESULTS: Young women reported fatigue, pain in the breast and hand problems with lymphedema as the most frequent physical effects of treatment. Other physical problems were the not periodic and painful menses, vaginal dryness and loss of libido. Many young women had depressive symptoms such as depressed mood, helplessness, hopelessness, sleep loss, psychomotor retardation and disorders of appetite. There were often concerns about the health monitoring and self-image, while they were anxious if they will have a baby in the future or if they can nurture the existing ones. Many problems arose in the career of young women. They faced discrimination in the labor supply and/or layoff because they were considered unable to do their job effectively. In addition, they reported isolation problems and feeling different from other women of similar age. CONCLUSIONS: Young women consider that their healthrelated QoL is worse compared with older women. Young women worry about their future, with particular reference to their role as mothers and especially to children-bearing. The free screening and non-exclusion of young women is particularly important for breast cancer prevention and women's well-being.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Ansiedade , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Criança , Depressão , Feminino , Nível de Saúde , Humanos
19.
Breast Care (Basel) ; 11(5): 339-344, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27920627

RESUMO

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have received considerable interest as potential chemopreventive agents. The aim of this review is to summarize the accumulated knowledge on the effect of NSAIDs on breast cancer incidence and natural history, and the underlying pathophysiology. NSAIDs mainly block inflammation by inhibiting cyclooxygenase enzymes, leading to lower prostaglandin synthesis. The latter has been reported to affect breast cancer risk through hormonal and inflammation-related pathways. Intensity, dose, frequency, duration, and timing of administration may also be significant. There is currently enough evidence to support a role of NSAIDs in breast cancer prevention and relapse, which deserves further large-scale experimental and clinical investigation.

20.
J BUON ; 21(2): 412-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27273952

RESUMO

PURPOSE: The aim of this study was to compare the feasibility, efficacy and safety of microwave ablation and saline-linked radiofrequency (Aquamantys) in liver resection. METHODS: Sixteen domestic pigs (8 per group) underwent thermoablations. Group A consisted of 8 pigs in which microwave left lateral liver resection was performed. Group B consisted of 8 pigs which underwent left lateral liver resection by the Aquamantys system. After 28 days of close follow-up, the animals were sacrificed in order to study the macroscopic and microscopic findings of each intervention on the liver edge. RESULTS: An average of 47.13 min was enough for the entire operation to take place using Aquamantys, whereas an average of 59.13 min was needed in the microwave liver resection group. Mean blood loss was 40 ml (range 5-85) with Aquamantys whereas mean blood loss was 72.37 ml (range 42-100) using microwave. Postoperative complications rates were extremely low in both groups. There was no intra- or postoperative mortality. CONCLUSIONS: Our study demonstrated that left lateral liver resection using Aquamantys system is technically feasible in the porcine model and proved to be highly effective and a safer hemostatic method compared to microwave ablation.


Assuntos
Técnicas de Ablação , Ablação por Cateter , Fígado/cirurgia , Micro-Ondas , Cloreto de Sódio/administração & dosagem , Técnicas de Ablação/efeitos adversos , Animais , Perda Sanguínea Cirúrgica , Ablação por Cateter/efeitos adversos , Estudos de Viabilidade , Fígado/patologia , Masculino , Micro-Ondas/efeitos adversos , Modelos Animais , Projetos Piloto , Complicações Pós-Operatórias/etiologia , Sus scrofa , Fatores de Tempo
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