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1.
Neurology ; 94(5): e521-e528, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31907288

RESUMO

OBJECTIVE: The primary objective was to determine the sensitivity and specificity of epithelial cell adhesion molecule (EpCAM) immunoflow cytometry circulating tumor cells (CTC) analysis in CSF in patients with suspected leptomeningeal metastases (LM). The secondary objective was to explore the distribution of driver mutations in the primary tumor, plasma, cell free CSF (cfCSF), and isolated CTC from CSF in non-small cell lung cancer (NSCLC). METHODS: We tested the performance of the CTC assay vs CSF cytology in a prospective study in 81 patients with a clinical suspicion of LM but a nonconfirmatory MRI. In an NSCLC subcohort, we analyzed circulating tumor (ct)DNA of the selected driver mutations by digital droplet PCR (ddPCR). RESULTS: The sensitivity of the CTC assay was 94% (95% confidence interval [CI] 80-99) and the specificity was 100% (95% CI 91-100) at the optimal cutoff of 0.9 CTC/mL. The sensitivity of cytology was 76% (95% CI 58-89). Twelve of the 23 patients with NSCLC had mutated epidermal growth factor receptor (EGFR). All 5 tested patients with LM demonstrated the primary EGFR driver mutation in cfCSF. The driver mutation could also be detected in CTC isolated from CSF. CONCLUSION: CTC in CSF are detected with a high sensitivity for the diagnosis of LM. ddPCR can determine EGFR mutations in both cfCSF and isolated CTC from CSF of patients with EGFR-mutated NSCLC and LM. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that EpCAM-based immunoflow cytometry analysis of CSF accurately identifies patients with LM.


Assuntos
Carcinoma/líquido cefalorraquidiano , Carcinomatose Meníngea/líquido cefalorraquidiano , Células Neoplásicas Circulantes , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma/diagnóstico , Carcinoma/secundário , Carcinoma Ductal de Mama/líquido cefalorraquidiano , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/líquido cefalorraquidiano , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/secundário , Carcinoma Pulmonar de Células não Pequenas/líquido cefalorraquidiano , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células de Transição/líquido cefalorraquidiano , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/secundário , Molécula de Adesão da Célula Epitelial , Receptores ErbB/genética , Feminino , Citometria de Fluxo , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Imagem por Ressonância Magnética , Masculino , Carcinomatose Meníngea/diagnóstico , Carcinomatose Meníngea/genética , Carcinomatose Meníngea/secundário , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/líquido cefalorraquidiano , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/secundário
2.
Am J Surg Pathol ; 44(1): 77-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403964

RESUMO

Metastatic invasive lobular carcinoma (mILC) may masquerade as primary diffuse gastric adenocarcinoma (PDGA) by demonstrating significant clinical and pathologic overlap. Accurate distinction is of therapeutic and prognostic significance. On the basis of anecdotal cases of mILC that lacked estrogen receptor and/or GATA3 expression, we analyzed the cytoarchitectural features of 28 mILC and 44 PDGA specimens obtained from women to assess features that would help in this distinction and prompt ancillary work-up. In addition to performing an interobserver agreement analysis among 3 pathologists, we also evaluated SATB2 expression in this setting. Eighteen of 20 (90%) patients had a history of ILC. The mean interval between initial diagnosis of breast cancer and metastasis was 7.3 years (range: 1 to 36 y). Compared with mILC, PDGA was significantly associated with full-thickness mucosal involvement (47% vs. 80%; P=0.015), a nested/sheet-like growth pattern (32% vs. 68%; P=0.004), anastomosing cords (0% vs. 100%; P=0.001), multivacuolated cells (0% vs. 61%; P<0.0001), pleomorphic nuclei (4% vs. 70%; P<0.0001) and enlarged nuclei (4% vs. 70%; P<0.0001). Single file growth pattern (P<0.0001) and superficial lamina propria involvement (P=0.009) were more common in mILC. Estrogen receptor and GATA3 were expressed in all but 5 mILC cases; SATB2 was only seen in 30% of PDGA cases. Our results demonstrate that in a biopsy specimen, careful morphologic assessment can be extremely helpful in distinguishing mILC from PDGA and guiding ancillary work-up, especially when a history of breast cancer may not be readily available or when the neoplasm lacks expression of conventional breast markers.


Assuntos
Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundário , Diagnóstico Diferencial , Feminino , Fator de Transcrição GATA3/biossíntese , Humanos , Pessoa de Meia-Idade , Receptores Estrogênicos/biossíntese , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/secundário
3.
Anticancer Res ; 39(11): 6183-6192, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704846

RESUMO

AIM: To investigate the feasibility of hookwire-guided sentinel lymph node biopsy (SLNB) using contrast-enhanced ultrasonography (CEUS) followed by a one-step nucleic acid amplification (OSNA) assay. PATIENTS AND METHODS: Clinical T1-2N0M0 breast cancer patients scheduled to undergo SLNB participated in this study. Both Sonazoid® and dye were used as tracers, and the most upstream sentinel lymph node (SLN) at each lymphatic flow detected by CEUS (First-SLN) was sampled under hookwire guidance, a procedure called "Sona-Hook". RESULTS: In each of the 50 cases, at least one First-SLN was extracted by "Sona-Hook". All contrast-enhanced SLNs (CE-SLNs) were dye-positive, and the mean number of CE-SLNs sampled per patient was lower than that of dye-positive SLNs (1.48 vs. 1.88, p<0.01). Through OSNA, qualitative assessment of tumor metastasis between First-SLNs and all SLNs completely matched together. CONCLUSION: "Sona-Hook" for First-SLN followed by an OSNA assay may be a feasible minimally invasive SLNB strategy.


Assuntos
Neoplasias da Mama/patologia , Meios de Contraste , Biópsia Guiada por Imagem/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Linfonodo Sentinela/patologia , Ultrassonografia Mamária/métodos , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/genética , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Prognóstico , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia
4.
Chirurgia (Bucur) ; 114(5): 571-578, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670632

RESUMO

Introduction: The predilection of lobular invasive breast cancer metastasis for the stomach is a topic that has succumbed to various assumptions over the time. Background and Aims: Gastric metastasis of lobular breast cancer is unusual and it can be diagnosed after a long period of time from primary tumor diagnosis. The aim of this study was to review current knowledge regarding the current methods of diagnosis and treatment of gastric metastasis of breast cancer. Methods: A systematic literature search was performed in the Pub-Med Medline database using the terms "gastric metastasis of lobular breast cancer" and "gastric metastasis features" to identify articles relevant to gastric metastasis of lobular breast cancer. Results: Several papers have shown that the topic is rarely presented in the form of case presentations or miniseries by summing up sporadic cases. Due to its rarity and metastasis specificity as host type and appearance after latency of lobular breast cancer makes its gastric metastasis considered atypical and occasionally confused with a primary stomach malignancy. The most recent articles present the immunohistochemical diagnostic criteria of this clinical entity and a new therapeutic approach. Conclusion: At patients with gastric metastasis of lobular breast cancer, obtaining pathologic material and biopsies interpretation can be a real challenge for getting a correct pathologic diagnosis, immunohistochemistry gives us definite diagnosis. The introduction of an endoscopic surveillance protocol for patients with lobular breast cancer could be a proposal for the detection of early gastric metastases allowing for appropriate therapy.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Lobular/diagnóstico , Neoplasias Gástricas/diagnóstico , Carcinoma Lobular/secundário , Feminino , Humanos , Neoplasias Gástricas/secundário
6.
Surg Oncol ; 30: 141-146, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500779

RESUMO

BACKGROUND: The oncologic benefit of upfront re-excision of involved margins after breast-conserving surgery in the context of current multimodal clinical management of breast cancer is unclear. The aim of the present study was to assess the 5-years locoregional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in patients not undergoing re-excision of positive margins after lumpectomy for breast cancer. METHODS: A cohort of 104 patients with positive margins not undergoing re-excision was matched by propensity score with a cohort of 2006 control patients with clear margins after breast-conserving surgery, treated between 2008 and 2018. A multivariate survival analysis was performed accounting for all variables related to LRR and DM, including adjuvant treatments. RESULTS: After adjusting for potential confounders, avoiding to re-excise a positive margin after lumpectomy had no effect on 5-years LRR-free survival probability (HR 0.98, 95%CI 0.36-2.67, p = 0.96) or 5-years DM-free survival probability (HR 0.37, 95%CI 0.08-1.61, p = 0.18). No correlation was found between occurrence of LRR and number of involved margins (HR 1.28, 95%CI 0.10-12.4, Log-rank p = 0.83), or extension of infiltrating disease (HR 1.21, 95%CI 0.20-7.40, Log-rank p = 0.83), but a trend toward higher LRR probability was found for invasive ductal (HR 6.92, 95%CI 0.7-68.8, Log-rank p = 0.10) and invasive lobular cancer (HR 12.95, 95%CI 0.79-213.6, Log-rank p = 0.07) on positive margins. CONCLUSIONS: In the era of multimodal treatment of breast cancer and accurate strategies to reduce the probability of residual disease in the post-lumpectomy cavity, re-excision of positive margins might be omitted in selected patients with low-risk breast cancers.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Lobular/mortalidade , Margens de Excisão , Mastectomia Segmentar/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida
7.
Ann Surg Oncol ; 26(11): 3455-3461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332637

RESUMO

BACKGROUND: Breast cancer patients with local and/or locoregional recurrence (LR) are at higher risk of developing distant metastases (DM) at a later time. Once LR has been confirmed, some international interdisciplinary guidelines recommend performing radiological examinations for DM to determine the course of further therapy (curative or palliative approach). This study analyzed the metastatic patterns of patients with LR with particular regard to the frequency of concurrent diagnosis of LR and DM; in other words: are radiological staging procedures actually justified for DM at the time of diagnosis of LR? METHODS: This study included all patients (n = 1368) who were diagnosed and treated for nonmetastatic breast cancer (Stage I-III) at the University Women's Hospital Basel, Switzerland between 1990 and 2009. RESULTS: In 137 patients, LR was diagnosed without a history of DM: in-breast/thoracic wall only, n = 90 (65.7%); involvement of axillary/supra-/infraclavicular lymph nodes, n = 47 (34.3%). DM was found at the time of diagnosis of LR in 44 patients (32.1%). Concurrent diagnosis of LR and DM occurred significantly more often in patients with lymph node recurrence compared with those with in-breast/chest wall recurrence (48.9% vs. 23.3%; p = 0.004). CONCLUSIONS: Approximately one-third of patients with a LR had synchronous DM at the time of their local/locoregional event. For this reason, routine systemic staging imaging at the time of LR should be an absolute requirement for planning further therapy. Confirmation of DM may spare the patients radical surgical interventions with questionable impact on survival in the face of an incurable disease.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Guias de Prática Clínica como Assunto/normas , Parede Torácica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Prospectivos , Parede Torácica/diagnóstico por imagem , Parede Torácica/cirurgia
8.
J Surg Oncol ; 120(4): 578-586, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31338839

RESUMO

BACKGROUND: This study aimed to develop an easy to use prediction model to predict the risk of having a total of 1 to 2, ≥3, or ≥4 positive axillary lymph nodes (LNs), for patients with sentinel lymph node (SLN) positive breast cancer. METHODS: Data of 911 SLN positive breast cancer patients were used for model development. The model was validated externally in an independent population of 180 patients with SLN positive breast cancer. RESULTS: Final pathology after ALND showed additional positive LN for 259 (28%) of the patients. A total of 726 (81%) out of 911 patients had a total of 1 to 2 positive nodes, whereas 175 (19%) had ≥3 positive LNs. The model included three predictors: the tumor size (in mm), the presence of a negative SLN, and the size of the SLN metastases (in mm). At external validation, the model showed a good discriminative ability (area under the curve = 0.82; 95% confidence interval = 0.74-0.90) and good calibration over the full range of predicted probabilities. CONCLUSION: This new and validated model predicts the extent of nodal involvement in node-positive breast cancer and will be useful for counseling patients regarding their personalized axillary treatment.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Linfonodos/patologia , Nomogramas , Linfonodo Sentinela/patologia , Idoso , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
9.
J Surg Oncol ; 120(4): 587-592, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309573

RESUMO

BACKGROUND: We implemented selective use of frozen section (FS) to optimize accuracy and cost control in the intraoperative diagnosis of sentinel lymph node (SLN) in patients with breast cancer, guided by the Memorial Sloan Kettering Cancer Center (MSKCC) nodal metastasis risk prediction nomogram. METHODS: Surgical pathology records were reviewed, examining 2582 consecutive biopsies from 2552 patients with breast cancer to compare intraoperative FS diagnoses with postoperative final reports. We calculated sensitivity, specificity, and false-negative rates (FNRs) for various MSKCC risk levels, also analyzing axillary reoperation rates, with and without FS, and the number needed to treat (NNT) to avoid separate axillary lymph node dissection. RESULTS: The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3%, respectively. FNR and MSKCC risk level negatively correlated (r = -0.86; P = .002). Axillary reoperation rate significantly declined if FS was done (FS: 4.0%; no FS: 36.4%; P = .002). In grouping patients by quartile of MSKCC risk, axillary reoperation rates were 16.7%, 25.1%, 38.7%, and 58.7% without FS, compared with 4.3%, 3.2%, 5.6%, 3.3% with FS and NNT correspondingly fell from 8.1 to 4.6, 3.0, and 1.8. CONCLUSIONS: A stratified decision-making algorithm based on the MSKCC risk prediction model improved the effectiveness of FS during SLN biopsy to avoid axillary reoperation.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Secções Congeladas/normas , Linfonodos/patologia , Nomogramas , Biópsia de Linfonodo Sentinela/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Cuidados Intraoperatórios , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Adulto Jovem
10.
BMC Cancer ; 19(1): 626, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238899

RESUMO

BACKGROUND: Sentinel node biopsy (SNB) is the standard procedure for axillary staging in patients with clinically lymph node negative invasive breast cancer. Completion axillary lymph node dissection (c-ALND) may not be necessary for all patients as a significant number of patients have no further metastases in non-sentinel nodes (non-SN) and c-ALND may not improve survival. The first aim of our study is to identify clinicopathological determinants associated with non-SN metastases. The second aim is to determine the impact of the number of sentinel node (SN) with macro-metastases and the type of SN metastases on metastatic involvement in non-SN. METHODS: This is a retrospective study of 602 patients with primary invasive breast cancer operated on with SNB and c-ALND in Lund and Malmö during 2008-2013. All these patients had micro- and/or macro-metastases in SNs. Information was retrieved from the national Information Network for Cancer Care (INCA). The risk of metastases to non-SNs were analyzed in relation to clinicopathological determinants such as age, screening mammography, tumour size, tumour type, histological grade, estrogen status, progesterone status, HER2 status, multifocality and lymphovascular invasion. Additionally, we compared the association between the number of the SN and the type of metastases in SN with the risk of metastases to non-SNs. Binary logistic regression was used, yielding odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We found that 211 patients (35%) had metastases in non-SNs and 391 patients (65%) had no metastases in non-SNs. Lobular type (18%) of breast cancer (1.73; 1.0 1-2.97) and multifocal (31.3%) tumours (2.20; 1.41-3.44) had a high risk of non-SNs metastases. As compared to only micro-metastases, the presence of macro-metastases in SNs was associated with a high risk of metastases to non-SNs (4.91; 3.01-8.05). The number of SN with macro-metastases, regardless of the number of SNs removed by surgery, increases the risk of finding non-SNs with metastases. The total number of SN removed by surgery had no impact on diagnosis of metastases in non-SNs. No statistically significant associations were observed regarding other studied determinants. CONCLUSION: We conclude in the present study that lobular cancer and multifocal tumours were associated with a high risk of non-SN involvement. The presence of the macro-metastases in SNs and the number of SN with macro-metastases has a positive association with presence of metastases in non-SNs. The total number of SNs removed by surgery had no impact on finding metastases in non-SNs. These factors may be valuable considering whether or not to omit c-ALND.


Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Metástase Linfática/patologia , Adulto , Fatores Etários , Idoso , Axila , Biópsia , Carcinoma Lobular/patologia , Carcinoma Lobular/secundário , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Micrometástase de Neoplasia/patologia , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Carga Tumoral
11.
Ann Surg Oncol ; 26(12): 3846-3855, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31222687

RESUMO

BACKGROUND: Recent trials have demonstrated the feasibility of sentinel lymph node biopsy (SLNB) for cN1 breast cancer patients after neoadjuvant chemotherapy (NAC). This study evaluated the technical outcomes of SLNB by residual nodal disease volume. METHODS: From a prospective database, cT1-3 cN1 patients receiving NAC and surgery from 2016 to 2017 were identified. Performance measures of post-NAC physical exam and imaging-based axillary assessment were compared. For the patients who converted to cN0 and underwent SLNB, adequate mapping (defined as ≥ 3 SLN) and the false-negative rate (FNR) of intraoperative SLN evaluation were assessed by residual nodal disease volume (ypN1-3 vs ypN0[i+]/ypN1mi vs ypN0). RESULTS: Of 156 cT1-3 cN1 patients, 96 converted to cN0 and underwent SLNB. Adequate mapping was achieved for 64 patients (66.7%) and was not associated with nodal volume (p = 0.12). The FNR of the intraoperative SLN evaluation was 37.8%, and smaller nodal volume was associated with FNR (p < 0.01). Of 36 patients (37.5%) who achieved an axillary pathologic complete response, 24 (66.7%) had three or more negative SLNs and were safely spared axillary lymph node dissection (ALND). The positive predictive values of physical exam versus imaging-based post-NAC nodal assessment were respectively 88% and 69.8%. CONCLUSIONS: This study showed SLNB to be an effective tool for minimizing axillary surgery in cN1 patients treated with NAC. However, important technical limitations exist, such as inability to identify three SLNs in more than two-thirds of patients and high-false negative rates for intraoperative SLN evaluation, particularly for patients with small residual nodal volumes. Preoperative counseling should include realistic assessment of the potential need for ALND in this population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasia Residual/mortalidade , Biópsia de Linfonodo Sentinela/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Prognóstico , Estudos Prospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Taxa de Sobrevida
13.
Crit Rev Oncol Hematol ; 135: 85-94, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30819451

RESUMO

Leptomeningeal carcinomatosis (LC) is defined as infiltration of the leptomeninges by metastatic carcinoma, a relatively uncommon but devastating complication of many malignancies. Although only 5% of patients with breast cancer develop leptomeningeal involvement, it remains the most common etiology of LC. It can occur as a late-stage complication of systemic progression or present as the first sign of metastatic disease, with or without parenchymal brain metastases. Lobular carcinomas have a higher propensity to metastasize into the meninges when compared to ductal carcinoma, especially the triple-negative subtype, which usually is associated with a shorter interval between metastatic breast cancer diagnosis and the development of LC. Prognosis remains poor, with median survival of 4 months for patients receiving state-of-the-art treatment. The main factors associated with survival are performance status at diagnosis, CSF protein level and triple-negative subtype. Headache is commonly the first clinical presentation of LC, and the diagnostic workup usually requires CSF-cytological analysis and or/MRI. The current management of LC consists of a combination of intra-CSF chemotherapy, systemic therapy, radiotherapy and/or best-supportive care. The standard intra-CSF chemotherapy regimen is methotrexate. Radiotherapy is used for relieving obstruction points on CSF-outflow channels due to ependymal nodules, tumor deposits or bulky disease. Objective responses have been reported with intrathecal administration of trastuzumab for HER2-positive disease, yet this strategy is still under investigation. Further prospective trials are needed to better address the impact of these treatment modalities on overall survival and quality of life.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Carcinomatose Meníngea/secundário , Feminino , Humanos , Prognóstico
14.
Cancer Treat Res Commun ; 19: 100123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30826563

RESUMO

BACKGROUND: Breast cancer has, due its high incidence, the highest mortality of cancer in women. The most common molecular variety of breast cancer is luminal subtype that expresses estrogen and progesterone receptors. Estrogen receptor alpha (ERα), encoded by the estrogen receptor1 (ESR1) gene, is expressed in approximately 70% of all breast cancers, and hormonal therapy represents a major treatment modality in all stages of ER positive breast cancers. Acquired mutations in the ligand-binding domain (LBD) of ERα, referred as ESR1 mutation, result in resistance to different endocrine therapies leading to disease progression or recurrence. Recent studies reviled that these ESR1 mutations lead to constitutive activity of the estrogen receptor ER, meaning that the receptor is active in absence of its ligand conferring resistance against endocrine therapy and tumor growth. Published studies have not yet been able to determine the exact prevalence rate of ESR1 mutations, but set the outer boundaries between 11-55%. PURPOSE: The goal of the present study is to determine the frequency rate of ESR1 mutations in ER positive recurrent breast cancer by using digital droplet PCR (ddPCR) technique. MATERIALS AND METHODS: This retrospective study was conducted in the Multidisciplinary Breast Clinic of Antwerp University Hospital. The seven most common ESR1mutations (c.1138G>C (p. (E380Q)), c.1610A>G (p.(Y537C)), c.1613A>G (p.(p.D538G)), c.1607T>G (p.(L536R)), c.1387T>C (p.S463R)), c.16410A>C (p.(Y537S)), c.609T>A (p.(Y537N)) were assessed in available baseline plasma samples of 21 patients with ER positive recurrent breast cancer. Inclusion criteria for study participation were: female, age above 18 years, ER positive breast cancer, 5years adjuvant hormonal therapy of primary disease, and disease recurrence or metastasis during or after stop of endocrine therapy. ESR1 mutations were analyzed in cell-free DNA (cfDNA) by using digital droplet PCR (ddPCR). RESULTS: cfDNA was obtained from 21 patients with recurrent breast cancer. ESR1 mutations were found in 4/21 (19%; 95% CI, 5%-42%). The test sensitivity was lower than the targeted value <0.1% in 29% of patients (6/21). No significant statistical difference in baseline clinical characteristics was observed in patients with wild-type and mutant ER (p>0.05). Adjuvant endocrine therapy for primary disease was Tamoxifen (TAM) for 57% of patients (12 of 21) of whom 8 patients had received aromatase inhibitor (AI) after two years, while 43% of patients (9 of 21) had received AI as first line adjuvant hormonal therapy. All the patients had received aromatase inhibitor AI therapy in first or second line therapy with initially a variable period of good response. CONCLUSION: ESR1 mutation analysis could be determined in archived plasma samples using simple non-invasive methods. In the future, screening for mutation status could improve the therapeutic strategies in controlling ER signaling before the occurrence of wide spread disease metastasis.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Receptor alfa de Estrogênio/genética , Mutação , Recidiva Local de Neoplasia/genética , Adulto , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Ácidos Nucleicos Livres/análise , Análise Mutacional de DNA , Receptor alfa de Estrogênio/sangue , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prevalência , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Rev Esp Enferm Dig ; 111(4): 326-328, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30859840

RESUMO

Colon metastases from breast carcinoma are relatively rare and the invasive lobular subtype tends to metastasize more frequently due to its peritoneal dissemination. A 67-year-old female with a lobular subtype breast neoplasm was treated via a surgical resection ten years previously, with subsequent radiotherapy and adjuvant chemotherapy. She is currently in clinical remission. A colonoscopy was performed due to a recent onset cachexia syndrome, which identified diffuse linitis plastica of the colon. Biopsies confirmed that it was secondary to infiltration by cancer cells of invasive lobular breast carcinoma (ILBC). In conclusion, linitis plastica of the colon may be a new presentation of colon metastases from ILBC.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Lobular/secundário , Neoplasias do Colo/secundário , Linite Plástica/secundário , Idoso , Neoplasias da Mama/terapia , Carcinoma Lobular/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Linite Plástica/tratamento farmacológico , Linite Plástica/patologia
16.
Cancer Treat Res Commun ; 19: 100121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785027

RESUMO

PURPOSE: This retrospective study of community oncology patients with breast cancer gene (BRCA)-mutated metastatic breast cancer (MBC) examined treatment outcomes and health resource utilization (HRU) and costs for a sample of patients with human epidermal growth factor receptor 2 (HER2)-negative disease who were either hormone receptor positive (HR+) or triple negative breast cancer (TNBC). METHODS: Evidence from the Vector Oncology Data Warehouse, a repository of electronic medical records/billing data and provider notes, was analyzed. Treatment outcomes were progression-free survival (PFS) and overall survival (OS) from start of first-line therapy in the metastatic setting. HRU and cost measures were collected from the time of MBC diagnosis to end of the record. HRU included hospitalizations, emergency room visits, infused/parenteral supportive care drugs, and outpatient visits. Costs were computed both as total and monthly costs. RESULTS: 57 HR+ and 57 TNBC patients (2013-2015) met inclusion criteria. Eight TNBC patients did not get treatment. HR+ patients had median first line PFS of 12.1 months and TNBC patients had 6.1 months. HR+ patients had median OS from start of first line of 38.4 months, and TNBC patients had 23.4 months. Rate of use of infused/parenteral supportive care drugs was 25.5% overall and 36.7% among TNBC patients with 15.8% among HR+ patients. CONCLUSION: There is an unmet need in BRCA-mutated patients with MBC, including those with HR+ and TNBC disease. The unmet need among TNBC patients was most evident in that 12% were not treated and TNBC patients appeared to have poor treatment outcomes. MICRO ABSTRACT: Reviewed medical records for outcomes, resource utilization, and costs in 114 community patients with BRCA mutated metastatic breast cancer. 57 hormone positive (HP); 57 triple negative (TN). RESULTS: median PFS: 12.1 months HP; 6.1 TN. HP OS was 38.4; TN 23.4. Rate of infused supportive care drugs: 25.5% HP; 36.7% TN. Patients with TN disease need better therapeutic options.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Custos e Análise de Custo , Alocação de Recursos para a Atenção à Saúde/estatística & dados numéricos , Mutação , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/economia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/economia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/economia , Carcinoma Lobular/genética , Carcinoma Lobular/secundário , Centros Comunitários de Saúde , Feminino , Seguimentos , Alocação de Recursos para a Atenção à Saúde/economia , Humanos , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Neoplasias Inflamatórias Mamárias/economia , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/secundário , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
Technol Cancer Res Treat ; 18: 1533033819828709, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30786836

RESUMO

BACKGROUND: MicroRNAs contribute to chemotherapy response in different types of cancer. We hypothesized that plasma miRNAs are potentially associated with chemotherapy response in patients with metastatic breast cancer. PATIENTS AND METHODS: Fourteen candidate microRNAs were chosen from the literature, and their plasma levels were measured by quantitative polymerase chain reaction (PCR). Forty metastatic breast cancer patients were chosen as the training groups. The potential significant microRNAs were validated in another 103 plasma samples. RESULTS: In the training set, we identified 3 microRNAs (miR-200a, miR-210, and miR-451) as significantly dysregulated miRNAs between sensitive group (partial response (and stable disease) and resistant group (progressive disease). Then, in the validation set, miR-200a (area under the curve = 0.881, sensitivity = 94.1%, specificity = 76.7%) and miR-210 (area under the curve = 0.851, sensitivity = 88.2%, specificity = 72.1%) showed high diagnostic accuracy for distinguishing sensitive group from resistant group. Furthermore, the plasma level of miR-200a was significantly associated with the stage in surgery ( P = .035), and the high level of miR-210 expression was associated with internal organ metastasis (liver, lung, and brain; P = .024). CONCLUSIONS: Plasma miR-200a and miR-210 could be effective biomarkers for the prediction of chemotherapy resistance in metastatic breast cancer patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/sangue , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Estudos de Casos e Controles , Feminino , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Prognóstico , Curva ROC
18.
Virchows Arch ; 474(3): 333-339, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30607556

RESUMO

Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Carcinoma de Células Escamosas/patologia , Neoplasias da Bexiga Urinária/secundário , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/química , Carcinoma Lobular/mortalidade , Carcinoma Lobular/terapia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Fatores de Tempo , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia
19.
Clin Breast Cancer ; 19(1): 1-9, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30245148

RESUMO

BACKGROUND: Eribulin mesylate is a non-taxane microtubule inhibitor effective in the treatment of metastatic breast cancer refractory to anthracyclines and taxanes. In preclinical studies, additional mechanisms of eribulin included reversal of epithelial mesenchymal transition and tumor vascular remodeling. The present study compared the safety and efficacy of eribulin plus cyclophosphamide (ErC) to docetaxel plus cyclophosphamide (TC) as neoadjuvant therapy for operable HER2- breast cancer. PATIENTS AND METHODS: Women with invasive HER2- breast adenocarcinoma with no distant metastases were eligible. After a 10-patient safety lead-in, the patients were randomized 2:1 to receive either ErC (eribulin 1.4 mg/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1) or TC (docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1) administered every 21 days for 6 cycles, followed by surgery. The pathologic complete response (pCR) rate was the primary endpoint. Tumor samples collected at baseline and at surgery were assayed for select epithelial mesenchymal transition and vascular density markers: E-cadherin, vimentin, and CD31 expression. RESULTS: A total of 76 patients were enrolled. Of the 76 patients, 10 received ErC in the lead-in phase and 66 were randomized to ErC (n = 44) or TC (n = 22). The pCR rates with ErC and TC were 13% and 9%, respectively. Both regimens produced frequent neutropenia and peripheral neuropathy. Both regimens increased vascular density as measured by CD31 staining. CONCLUSION: The neoadjuvant regimens of ErC and TC resulted in relatively low pCR rates in this patient population. No unexpected toxicities were observed. Our results also provided no suggestion that ErC is a neoadjuvant treatment with greater efficacy than that of standard regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Terapia Neoadjuvante/mortalidade , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Seguimentos , Furanos/administração & dosagem , Humanos , Cetonas/administração & dosagem , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida
20.
Cancer Chemother Pharmacol ; 83(1): 131-143, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30377778

RESUMO

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Padrões de Prática Médica , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/secundário , Docetaxel/administração & dosagem , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Adulto Jovem
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