Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
Cell Cycle ; 12(13): 2042-50, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23759596

RESUMO

The diagnosis of ductal carcinoma in situ (DCIS) is an increasingly common event due to widespread use of screening mammography. However, appropriate clinical management of DCIS is a major challenge in the absence of prognostic markers. Tumor-initiating cells may be particularly relevant for disease pathogenesis; therefore, two markers associated with such cells, EZH2 and ALDH1, were evaluated. A cohort of 248 DCIS patients was used to determine the association of EZH2 and ALDH1 with ipsilateral breast event, DCIS recurrence and progression to invasive breast cancer (IBC). In this cohort, high EZH2 expression was associated with the risk of an ipsilateral breast event and DCIS recurrence but not invasive progression. ALDH1 expression was observed in both the tumor and stromal compartment; however, in neither compartment were ALDH1 levels independently associated with evaluated study endpoints. Interestingly, the combination of high EZH2 with high epithelial ALDH1 was associated with disease progression. Therefore, ALDH1 within the DCIS lesion can add to the prognostic significance of EZH2, particularly in the context of risk of development of invasive disease.


Assuntos
Neoplasias da Mama/enzimologia , Carcinoma Intraductal não Infiltrante/enzimologia , Isoenzimas/metabolismo , Recidiva Local de Neoplasia/enzimologia , Complexo Repressor Polycomb 2/metabolismo , Retinal Desidrogenase/metabolismo , Família Aldeído Desidrogenase 1 , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Humanos , Isoenzimas/genética , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Complexo Repressor Polycomb 2/genética , Retinal Desidrogenase/genética , Fatores de Risco
2.
Breast J ; 19(3): 269-75, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23614365

RESUMO

Oncotype DX, a gene-expression profiling assay, provides stratification of patients with estrogen-receptor positive, lymph-node-negative early breast cancer into risk groups based on recurrence score, which are associated with distant recurrence and response to chemotherapy. This study aims to determine whether Oncotype DX influences clinicians' treatment decisions, and whether assay results correlate with histologic assessment. Fifty patients with estrogen-receptor positive, node-negative early breast cancer analyzed by Oncotype DX and operated on by two breast surgeons were included. To assess effect on treatment decisions, clinical vignettes were created by retrospective chart review. Physicians were then presented with the clinical vignettes and instructed to make a treatment decisions (i.e., hormone therapy alone versus hormone therapy combined with chemotherapy) both before and after knowledge of the recurrence score. To assess correlation with histologic assessment, a prospective, blinded review of tumor slides was performed by two pathologists. Based on this review, tumors were placed into low, intermediate and high risk groups for comparison with Oncotype DX assay results. Treatment decisions were changed based on Oncotype DX results in 36 and 18% of cases by breast surgeons and medical oncologists, respectively. All tumors categorized as high risk by Oncotype DX were categorized as high risk based on histologic assessment, and 96% of cases categorized as low risk by recurrence score were categorized as low or intermediate risk by histologic assessment. Oncotype DX significantly influences management of estrogen-receptor positive, lymph-node-negative early breast cancer. Further studies are needed to assess association of histologic categorization to assay results.


Assuntos
Neoplasias da Mama/cirurgia , Perfilação da Expressão Gênica , Receptores de Estrogênio/análise , Adulto , Idoso , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Medição de Risco
3.
Am Surg ; 79(3): 232-4, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23461945

RESUMO

John Chalmers DaCosta was an influential chairman and the first Samuel D. Gross Professor of Surgery at Jefferson Medical College in Philadelphia. He was well known throughout the field as a skilled surgeon, passionate speaker, and exceptional writer. In addition to countless accomplishments during his career, DaCosta was deeply dedicated to the preservation and commemoration of surgical history. This ideology was exemplified when he set out on a mission to recover the old wooden operating table used by many of his iconic mentors including Samuel D. Gross, Joseph Pancoast, and William W. Keen. This table was originally used for surgical demonstrations and anatomy lessons in a lecture room of the Ely Building and later in the great amphitheater of the Jefferson Sansom Street Hospital. It was found forgotten in the basement of the College Building and was promptly refurbished, donned with dedicatory plaques, and returned to its honored position in the medical college. Dr. DaCosta also contributed a detailed article recalling the history of the table and the notable leaders in surgery who taught and practiced on its surface. The old table currently stands proudly in the entranceway of the Department of Surgery where it will remain as a cherished symbol of the early beginnings of surgical practice and education.


Assuntos
Cirurgia Geral/história , Mesas Cirúrgicas/história , Desenho de Equipamento/história , Cirurgia Geral/instrumentação , História do Século XIX , História do Século XX , Humanos , Philadelphia
4.
J Natl Cancer Inst ; 104(23): 1825-36, 2012 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-23197489

RESUMO

BACKGROUND: A subset of patients with ductal carcinoma in situ (DCIS) will progress to invasive breast cancer. However, there are currently no markers to differentiate women at high risk from those at lower risk of developing invasive disease. METHODS: The association of two major tumor suppressor genes, retinoblastoma (RB) and phosphatase and tensin homolog (PTEN), with risk of any ipsilateral breast event (IBE) or progression to invasive breast cancer (IBC) was analyzed using data from 236 DCIS patients treated with breast conserving surgery with long-term follow-up. RB and PTEN expression was assessed with immunohistochemistry. The functional effects of RB and/or PTEN loss were modeled in MCF10A cells. Hazard ratios (HRs) were estimated with univariate and multivariable Cox regression models. All statistical tests were two-sided. RESULTS: Loss of RB immunoreactivity in DCIS was strongly associated with risk of IBE occurrence (HR = 2.64; 95% confidence interval [CI] = 1.64 to 4.25) and IBC recurrence (HR = 4.66; 95% CI = 2.19 to 9.93). The prognostic power of RB loss remained statistically significant in multivariable analyses. PTEN loss occurred frequently in DCIS but was not associated with recurrence or progression. However, patients with DCIS lesions that were both RB and PTEN deficient were at further increased risk for IBEs (HR = 3.39; 95% CI = 1.92 to 5.99) and IBC recurrence (HR = 6.1, 95% CI = 2.5 to 14.76). Preclinical modeling in MCF10A cells demonstrated that loss of RB and PTEN impacted proliferation, motility, and invasive properties. CONCLUSIONS: These studies indicate that RB and PTEN together have prognostic utility and could be used to target aggressive treatment for patients with the greatest probability of benefit.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Retinoblastoma/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Análise de Variância , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Retina
5.
Breast J ; 18(4): 303-11, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22759093

RESUMO

A consensus conference was held in order to provide guidelines for the use of adjuvant therapy in patients with Stage I carcinoma of the breast, using traditional information, such as tumor size, microscopic character, Nottingham index, patient age and co-morbidities, but also incorporating steroid hormone and Her-2-neu data as well as other immunohistochemical markers. The role of the genetic analysis of breast cancer and proprietary gene prognostic signatures was discussed, along with the molecular profiling of breast cancers into several groups that may predict prognosis. These molecular data are not currently sufficiently mature to make them part of decision making algorithms of recommendations for the treatment of individual patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Transcriptoma , Quimioterapia Adjuvante , Feminino , Regulação Neoplásica da Expressão Gênica , Testes Genéticos , Humanos , Micrometástase de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Biópsia de Linfonodo Sentinela
6.
Cancer ; 118(8): 2031-8, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22392361

RESUMO

BACKGROUND: Breast Health International and the Kimmel Cancer Center of Thomas Jefferson University cosponsored a consensus conference that included an international group of experts. METHODS: Since the adoption of adjuvant chemotherapy for stage I, lymph node-negative breast cancers in 1988, investigators have tried to "fine-tune" the treatment criteria. At this consensus conference, the group debated recommendations for adjuvant hormone and cytotoxic chemotherapy in stage I breast cancers. RESULTS: Discussions during the conference addressed issues of adjuvant therapy for stage I breast cancer and the influence of multigene analyses and molecular phenotyping. The panelists discussed various demographic, morphologic, biologic, and genetic factors expressed by individual tumors and their influence on treatment decisions. CONCLUSIONS: The panel tried to create guidelines for the consideration of adjuvant treatment of these patients, including both hormone and cytotoxic regimens. They also encouraged further research into the molecular analysis of breast cancers and the introduction of clinical trials based on current data, although they concluded that it is too early to add any of those analyses into the decision-making algorithms of recommendations for the treatment of stage I breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Combinada , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/metabolismo , Guias de Prática Clínica como Assunto
7.
J Am Coll Radiol ; 9(2): 137-40, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22305700

RESUMO

PURPOSE: A recent paper in the American Journal of Surgery reported that surgery is used for 30% of breast biopsies, an excessive number. The investigators' stated biopsy volume included Current Procedural Terminology(®) code 19125 ("excision of breast lesion identified by preoperative placement of radiological marker, open"). However, this code may often be used when a surgeon's primary intention is not biopsy but rather excision of a lesion. Therefore, the reported results may overstate the percentage of biopsies performed as surgical procedures. The aim of this study was to more accurately assess the use of percutaneous core needle biopsy (PNB) compared with surgical biopsy. METHODS: The nationwide Medicare Part B databases for 2004 to 2009 were used. Trends in use of codes 19100 (PNB without imaging), 19102 and 19103 (PNB with imaging), 19101 (open biopsy), and the aforementioned 19125 were determined. RESULTS: From 2004 to 2009, the volumes of PNB with imaging (codes 19102 and 19103) increased substantially, while the volume of code 19125 decreased substantially. If one includes all 19125 claims as biopsies, the 2009 frequency of surgical biopsies was 18%. If one considers all 19125 claims as excisions, the frequency of surgical biopsies was 2%. CONCLUSIONS: The previously published statement in the American Journal of Surgery that 30% of breast biopsies are done surgically is erroneous. Medicare data indicate that the true surgical breast biopsy figure is somewhere between 2% and 18%. Given that the recommended rate is 10%, it seems that surgeons and radiologists are collaborating well and that surgical breast biopsy is not being overused.


Assuntos
Biópsia por Agulha/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Mau Uso de Serviços de Saúde/estatística & dados numéricos , Mastectomia/estatística & dados numéricos , Procedimentos Cirúrgicos Minimamente Invasivos/estatística & dados numéricos , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Padrões de Prática Médica , Prevalência , Estados Unidos/epidemiologia
8.
Breast Cancer Res Treat ; 133(3): 1009-24, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22134623

RESUMO

Ductal carcinoma in situ (DCIS) is a precursor lesion that can gives rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue from pure DCIS and pure IBC were employed to define key gene expression profiles in either the epithelial or stromal compartment associated with disease progression. Each tissue had distinct gene expression profiles, and a DCIS/IBC classifier accurately distinguished DCIS versus IBC in multiple independent data sets. However, contrary to other studies that profiled DCIS associated with invasive disease, we found that the most significant alterations in gene expression were observed in the epithelial compartment rather than in the stroma. In particular, genes associated with epithelial-to-mesenchymal transition and myoepithelial cell-specific genes were enriched in invasive cancer relative to pure DCIS. Such alterations in transcript levels were associated with all subtypes of breast cancer, but were particularly indicative of poor outcome in ER-negative breast cancer. Together, these studies indicate that lesion-specific differences in gene expression associated with invasive phenotype are particularly relevant in the progression of DCIS to invasive breast cancer.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal/genética , Carcinoma Intraductal não Infiltrante/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal/mortalidade , Carcinoma Ductal/patologia , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/patologia , Análise por Conglomerados , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Receptores de Estrogênio/deficiência , Reprodutibilidade dos Testes , Células Estromais/metabolismo , Células Estromais/patologia , Análise de Sobrevida
9.
Am J Pathol ; 179(3): 1171-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21756866

RESUMO

The prevalence of ductal carcinoma in situ (DCIS) diagnoses has significantly increased as a result of active radiographic screening. Surgical resection and hormone and radiation therapies are effective treatments, but not all DCIS will progress to invasive breast cancer. Therefore, markers are needed to define tumors at low risk of recurrence and progression that can be treated by surgery alone rather than by adjuvant therapies. Initial analyses indicate that retinoblastoma (RB)-pathway perturbations occur at high frequency in DCIS and mirror the molecular alterations observed in invasive breast cancer. Particularly, the elevated expression of p16ink4a in DCIS was associated with loss of RB function and estrogen receptor-negative biology. Furthermore, high expression of p16ink4a in conjunction with Ki-67 was associated with increased risk of DCIS recurrence and progression to invasive disease in multivariate analyses. These data are consistent with a functional role for RB in modulating the invasive behavior of mammary epithelial cells. The tissue microenvironment is particularly relevant to the behavior of DCIS, and, surprisingly, elevated expression of p16ink4a in nonproliferative stroma was observed in a substantial fraction of cases. In this tissue compartment, p16ink4a expression was strongly associated with disease recurrence, independent of standard histopathologic features. Together, the data herein describe dual aspects of RB-pathway biology that are associated with disease recurrence through the epithelial or stromal compartment of DCIS.


Assuntos
Neoplasias da Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Genes do Retinoblastoma/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/cirurgia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Análise em Microsséries , Pessoa de Meia-Idade , Células Tumorais Cultivadas , Microambiente Tumoral/fisiologia
10.
Cancer ; 117(16): 3650-7, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21319154

RESUMO

BACKGROUND: Increased use of breast cancer screening has led to an increase in the number of diagnosed cases of ductal carcinoma in situ (DCIS). However, there is no definite way to predict progression or recurrence of DCIS. We analyzed the significance of biological markers and tumor characteristics in predicting recurrence in a large series of DCIS patients with long-term follow-up treated with breast conservation surgery (BCS) alone. METHODS: Clinical and pathological data were analyzed for 141 patients who underwent BCS for DCIS. All had negative surgical margins. Using local disease recurrence as an endpoint, we sought to determine the prognostic significance of several histopathological characteristics (tumor size, presence of necrosis, and subtype) and biological markers (estrogen receptor, progesterone receptor, and Her-2/neu.) RESULTS: At a median follow-up of 122 months (maximum follow-up, 294 months), 60 recurrences occurred, with a median time to recurrence of 191 months. On multivariate analysis, Her-2 positivity (3+) was found to be significantly associated with reduced time to tumor recurrence (P = .028). Tumor size and higher grade were marginally statistically significant (P = .099, P = .070). Neither necrosis nor tumor pathological characteristics were found to be significantly related to time to disease recurrence. CONCLUSIONS: Our results suggested that status of Her-2/neu, larger tumor size, and higher nuclear grade were significantly correlated with time to tumor recurrence in patients treated with BCS alone. Using logistical analyses, no significant correlation was found between tumor pathological characteristics and disease recurrence.


Assuntos
Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Biomarcadores Tumorais/análise , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Receptor ErbB-2/análise , Resultado do Tratamento
11.
Breast Cancer Res Treat ; 129(3): 717-24, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21088888

RESUMO

Hyperactivated HER2/Neu/EGFR/RAS signaling is a major growth-promoting pathway known to drive cellular transformation and oncogenesis in breast cancers. HER2 amplification is detected in ~20% of all human breast cancer and is quite prevalent (up to 49%) in ductal carcinoma in situ (DCIS). The E3 ubiquitin ligase SIAH is considered a key downstream "gatekeeper" required for proper HER2/EGFR/RAS signal transduction. Formalin-fixed, paraffin-embedded resection specimens from 65 patients with DCIS treated with wide excision only were stained with an anti-SIAH antibody, and the percentage of tumor and normal adjacent tissue cells positive for SIAH nuclear staining were recorded. Statistical analysis was performed comparing SIAH staining in tumor cells to disease recurrence, histologic type, necrosis, hormone receptor status, and Her2/neu status, as well as nuclear grade. Correlation of SIAH expression in tumor cells with SIAH expression in normal adjacent tissue and age was also examined. Expression levels of SIAH in tumor cells was significantly higher in specimens from patients with recurrence (median = 19%) as compared to patients without recurrence (7%) (P < 0.001). There was also significantly increased SIAH expression in tumors with more aggressive features including comedo morphology (13.5% in comedo vs. 7% in other histologic types, P = 0.014). No significant association was observed between SIAH expression and estrogen receptor, progesterone receptor, and Her2/neu status. There was a significant correlation between SIAH expression in tumors and normal adjacent tissue (Spearman correlation = 0.58, P < 0.001) as well as between SIAH expression in normal adjacent tissue and patient age (Spearman correlation = -0.59, P < 0.001). No significant correlation was identified between patient age and SIAH expression in tumors (Spearman correlation = -0.23, P = 0.067). In conclusion, SIAH may represent a useful prognostic biomarker that predicts DCIS progression to invasive breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/cirurgia , Progressão da Doença , Feminino , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Curva ROC , Valores de Referência
12.
Cancer Biol Ther ; 10(4): 391-6, 2010 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-20574156

RESUMO

The current classification of ductal carcinoma in situ (DCIS) is based on nuclear grade, architectural differentiation and the presence of necrosis that does not adequately predict the likelihood of recurrence after breast conserving therapy; therefore, there is a critical need to identify novel predictors of DCIS progression. Ninety seven cases of DCIS were included in the study. CD10 and SPARC expression in tumor stroma was assessed by standard immunoperoxidase method with ani-CD 10 and anti-SPARC antibodies. The staining was scored semi-quantitatively as negative, weak or strong. Statistical analysis was performed using the Fisher's exact test. Multivariable analysis was conducted utilizing Exact Logistic Regression software (SAS 9.1 and LogExact). A significant association was observed between the recurrence status and time to recurrence with expression of CD10 (p < 0.001) and SPARC (p < 0.001). When combining both SPARC and CD10 expression there was a strong correlation with the shortest time to recurrence. Stromal CD10 and SPARC expression are new markers of an increased risk for DCIS recurrence, independent of commonly assessed clinical parameters. Thus, stromal CD10 and SPARC expression levels are promising markers of DCIS recurrence and warrant evaluation in larger prospective studies.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Recidiva Local de Neoplasia , Neprilisina/metabolismo , Osteonectina/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Estadiamento de Neoplasias , Prognóstico , Células Estromais/metabolismo
13.
Cancer ; 116(5): 1243-51, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-20087958

RESUMO

BACKGROUND: The timing and accuracy of axillary sentinel lymph node biopsy (SLNB) in patients who are receiving neoadjuvant chemotherapy (NACT) for breast cancer are controversial. To examine the accuracy of SLNB after NACT, the authors performed SLNB after chemotherapy on all of patients who received NACT at their institution starting in January 1997. METHODS: Seventy-nine women who underwent NACT between 1997 and 2008 comprised this study and were divided as follows: 4 women had stage I disease, 60 women had stage II disease, and 15 women had stage III disease, including 10 women who had multicentric disease. Thirty-nine women (49.4%) had clinical evidence of axillary metastasis (N1-N2) at the time of diagnosis. The regimen, the duration of treatment, and the number of cycles of NACT depended on clinical response. The choice of breast conservation therapy or mastectomy was based on the patient's response to treatment and patient preference. All patients underwent SLNB after NACT. RESULTS: Seventy-three patients underwent breast conservation therapy, and 6 patients underwent mastectomy. Sentinel lymph nodes were identified in 98.7% of patients (in 1 patient, SLNB failed to capture 1 proven axillary metastasis), and 29 patients underwent full axillary lymph node dissection. Fourteen patients (17.7%) had no residual carcinoma (invasive or ductal carcinoma in situ) in their breast, 5 patients (6.3%) had residual ductal carcinoma in situ (only), and 60 patients (75.9%) had residual invasive carcinoma. One false-negative SLNB was reported in the group of 23 patients who underwent full axillary dissection after a negative SLNB. No patient had a subsequent axillary recurrence. CONCLUSIONS: SLNB after NACT was feasible in virtually all patients and accurately selected patients who required complete level I and II axillary dissection. NACT frequently downstaged the axilla, converting patients with N1-N2 lymph node status to N0 status and also avoiding full axillary dissection in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Terapia Neoadjuvante , Biópsia de Linfonodo Sentinela/métodos , Adulto , Idoso , Neoplasias da Mama/cirurgia , Carcinoma/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Tempo
14.
Cancer Biol Ther ; 8(11): 1071-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19502809

RESUMO

Here, we determined the possible association of stromal caveolin-1 (Cav-1) levels with DCIS recurrence and/or progression to invasive breast cancer. An initial cohort of 78 DCIS patients with follow-up data was examined. As ER-positivity was associated with recurrence, we focused our analysis on this subset of 56 patients. In this group, we observed that DCIS progressed to invasive breast cancer in approximately 14% of the patient population (8/56), in accordance with an expected progression rate of 12-15%. Nearly ninety percent of DCIS patients (7/8) that underwent recurrence to invasive breast cancer had reduced or absent levels of stromal Cav-1. Remarkably, an absence of stromal Cav-1 (score = 0) was specifically associated with early disease progression to invasive breast cancer, with reduced time to recurrence and higher recurrence rate. All DCIS patients with an absence of stromal Cav-1 underwent some form of recurrence (5/5) and the majority (4/5) underwent progression to invasive breast cancer. This represents an overall cumulative incidence rate of 100% for recurrence and 80% for progression. An absence of stromal Cav-1 in DCIS lesions was also specifically associated with the presence of inflammatory cells. Conversely, ninety-seven percent of ER(+) DCIS patients (35/36) with high levels of stromal Cav-1 (score = 2) did not show any invasive recurrence over the duration of follow-up (4-208 mo), and 89% of such patients are estimated to remain free of invasive recurrence, even after 15 y. Thus, determination of stromal Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS patients.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Caveolina 1/biossíntese , Recidiva Local de Neoplasia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia
15.
Breast J ; 15(1): 4-16, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19141130

RESUMO

A consensus conference including thirty experts was held in April, 2007, to discuss risk factors for breast cancer and their management. Four categories of risk were outlined, from breast cancer "average" through "very high" risk, the latter including individuals with high penetrance BRCA1/2 gene mutations. Guidelines for management of patients in each of these categories were discussed, with the major portion of the conference being devoted to individuals with BRCA1/2 mutations. Prevalence of these mutations in the general populations was estimated to be 1 in 250-500 individuals, with an increased prevalence in Ashkenazic Jews and other founder groups. Risk reduction strategies for these individuals include surveillance, with or without chemoprevention drugs, or surgical procedures to remove the organs at risk, i.e., bilateral mastectomy and/or bilateral salpingo-oophorectomy. These risk reduction strategies were evaluated fully, and recommendations were made for the care of patients in each of the risk categories. These guidelines for patient care were approved by the entire group of experts.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Gestão de Riscos , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Genes BRCA1 , Genes BRCA2 , Genes p53 , Aconselhamento Genético , Humanos , Mutação , PTEN Fosfo-Hidrolase/genética , Fatores de Risco
16.
Clin Cancer Res ; 14(24): 8244-52, 2008 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19088042

RESUMO

PURPOSE: Increased incidence of ductal carcinoma in situ (DCIS) associated with mammographic screening for breast cancer has emphasized the challenges of managing this condition. The aim of this study was to identify informative clinical indicators of DCIS biology by molecular profiling. EXPERIMENTAL DESIGN: Areas of in situ carcinoma, atypical ductal hyperplasia, and benign epithelium were microdissected from 46 invasive breast cancers. Oligonucleotide probes showing differential expression between DCIS associated with grade 1 and 3 invasive cancer were identified by microarray-based gene expression profiling. Expression at these probes was used to define a "molecular grade" subcategorization of all samples. The genomic basis of molecular grade was examined by array-based comparative genomic hybridization. Clinical course was examined in a cohort of 134 patients with DCIS treated by surgery alone. RESULTS: DCIS samples were designated as low or high molecular grade based on expression at 173 probes. The low molecular grade subgroup included low (n = 10) and intermediate (n = 11) nuclear grade DCIS as well as all samples of atypical ductal hyperplasia (n = 4) and benign epithelium (n = 7). The high molecular grade subgroup included DCIS of intermediate (n = 7) and high (n = 19) nuclear grade. The character and degree of genomic aberration were distinct between molecular grade subgroups. A classification tree model including nuclear grade and Ki67 score accurately predicted molecular grade for 95.7% of samples. In an independent cohort, this showed a pattern of rapid disease recurrence for high molecular grade DCIS. CONCLUSIONS: Molecular profiling indicates a binary grading scheme for DCIS. This practical approach has potential to improve clinical evaluation of DCIS.


Assuntos
Neoplasias da Mama/genética , Carcinoma in Situ/genética , Carcinoma Ductal de Mama/genética , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Dosagem de Genes , Perfilação da Expressão Gênica , Humanos , Microdissecção
17.
Cancer ; 113(10): 2627-37, 2008 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-18853415

RESUMO

A consensus conference including 30 experts was held in April, 2007, to discuss risk factors for breast cancer and their management. Four categories of risk were outlined, from "average" through "very high" risk, the latter including individuals with high penetrance BRCA1/2 gene mutations. Guidelines for management of patients in each of these categories were discussed, with the major portion of the conference devoted to individuals with BRCA1/2 mutations. Prevalence of these mutations in the general population was estimated to be 1 in 250-500 individuals, with an increased prevalence in Ashkenazi Jews and other founder groups. Risk-reduction strategies for these individuals included surveillance, with or without chemoprevention drugs, or surgical procedures to remove the organs at risk, ie, bilateral mastectomy and/or bilateral salpingo-oophorectomy. These risk reduction strategies were evaluated fully, and recommendations were made for the care of patients in each risk category. These guidelines for patient care were approved by the entire group of experts.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Neoplasias da Mama/cirurgia , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Mutação , Prevalência , Fatores de Risco , Gestão de Riscos
18.
J Am Coll Surg ; 207(5): 758-62, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18954790

RESUMO

BACKGROUND: The value of frozen sections in the intraoperative examination of sentinel nodes (SN) remains controversial. Accurate frozen sections will spare those patients with node metastasis from a second procedure to complete the axillary dissection. We examined our own experience with intraoperative examination of SN. STUDY DESIGN: Between January 1, 2006, and December 31, 2006, we performed 236 sentinel lymph node biopsy procedures that were read as "frozen-section-negative." An additional 47 sentinel lymph node biopsy patients were frozen-section-positive for metastatic disease and underwent immediate completion axillary dissection. At least 1 SN was found in all 283 women (100%). The number of patients with false-negative frozen sections was tallied; patient data were reviewed for a number of variables to see which factors might be associated with a false-negative result. RESULTS: Eleven patients had positive nodes on subsequent examination of the formalin-fixed, hematoxylin and eosin-stained slides; the false-negative rate of intraoperative frozen section was 4.7%. The sensitivity of the negative frozen section was > 95%. The following variables were compared for significance: pathologist, nuclear grade, histologic grade, margins, lymphovascular invasion, tumor type (ductal versus lobular), and estrogen receptor and progesterone receptor values. The only significant variables were lymphovascular invasion (p = 0.019) and presence of in situ ductal carcinoma (p = 0.001). CONCLUSIONS: Our data confirm the value of intraoperative examination of SN: > 95% sensitivity. Presence of in situ ductal carcinoma or lymphovascular invasion makes these tumors more likely than others to have micrometastases to SN overlooked.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma/secundário , Carcinoma/cirurgia , Secções Congeladas , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Estudos de Coortes , Reações Falso-Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
19.
Clin Breast Cancer ; 8(2): 187-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18621616

RESUMO

Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal indolent lymphoma with histopatholigic features similar to those of marginal zone B-cell lymphomas. Primary breast MALT lymphomas were first described by Lamovec and Jancar as a low-grade B-cell lymphoma in 1987. Herein, a case is presented of a patient with primary MALT lymphoma of the breast. Issues in diagnosis and breast-conservation treatment, as it pertains to primary MALT lymphoma of the breast, will be discussed.


Assuntos
Neoplasias da Mama/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Idoso , Neoplasias da Mama/radioterapia , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Zona Marginal Tipo Células B/radioterapia
20.
Cancer ; 110(4): 876-84, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17620276

RESUMO

BACKGROUND: Breast carcinomas in African-American patients appear to be more aggressive than in Caucasian patients due to multifactorial differences. METHODS: The authors compiled pathology data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database regarding stage, histologic grade, and estrogen receptor (ER) expression in breast carcinomas diagnosed in 197,274 African-American and Caucasian patients between 1990 and 2000, and the same information, along with nuclear grade, Ki-67, c-erb-B2, and p53 expression, in 2230 African-American and Caucasian patients diagnosed at Thomas Jefferson University Hospital between 1995 and 2002. Immunohistochemical markers were assayed in paraffin-embedded, formalin-fixed tissue stained with hematoxylin and eosin using antibodies to these proteins, with differences in expression analyzed by the chisquare test. RESULTS: In both databases, more African-American patients presented with advanced stage tumors and higher histologic (P < .001) and nuclear grade (P < .001) than Caucasian patients. African-American patients had less ER positivity (51.9% vs 63.1%; P < .001) but significantly higher Ki-67 (42.4% vs 28.7%; P < .001) and p53 expression (19.4% vs 13.1%; P < .05) than Caucasian patients with all stages of disease. In addition, the basal or "triple-negative" breast cancer phenotype was more common in African-American patients than in Caucasian patients (20.8% vs 10.4%; P < .0001), and was associated with higher histologic and nuclear grade (P < .0001). CONCLUSIONS: African-American patients with breast carcinomas are more likely than Caucasian patients to present with tumors that are of a later stage and higher grade, with higher Ki-67 expression and more ER negativity, thereby highlighting a greater need for early screening among African-American women. Molecular studies that may explain these differences, and correlations with survival, have been proposed to identify therapeutic targets.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/etnologia , População Branca/estatística & dados numéricos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Receptor ErbB-2/análise , Sistema de Registros/estatística & dados numéricos , Proteína Supressora de Tumor p53/análise , Estados Unidos/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA