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1.
Cell Immunol ; 397-398: 104805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38244265

RESUMO

PIM kinases are over-expressed by a number of solid malignancies including breast cancer, and are thought to regulate proliferation, survival, and resistance to treatment, making them attractive therapeutic targets. Because PIM kinases sit at the nexus of multiple oncodriver pathways, PIM antagonist drugs are being tested alone and in conjunction with other therapies to optimize outcomes. We therefore sought to test the combination of pharmacological PIM antagonism and Th1-associated immunotherapy. We show that the pan PIM antagonist, AZD1208, when combined in vitro with Th1 cytokines IFN-γ and TNF-α, potentiates metabolic suppression, overall cell death, and expression of apoptotic markers in human breast cancer cell lines of diverse phenotypes (HER-2pos/ERneg, HER-2pos/ERpos and triple-negative). Interestingly, AZD1208 was shown to moderately inhibit IFN-γ secretion by stimulated T lymphocytes of both human and murine origin, suggesting some inherent immunosuppressive activity of the drug. Nonetheless, when multiplexed therapies were tested in a murine model of HER-2pos breast cancer, combinations of HER-2 peptide-pulsed DCs and AZD1208, as well as recombinant IFN-γ plus AZD1208 significantly suppressed tumor outgrowth compared with single-treatment and control groups. These studies suggest that PIM antagonism may combine productively with certain immunotherapies to improve responsiveness.


Assuntos
Antineoplásicos , Compostos de Bifenilo , Neoplasias , Proteínas Proto-Oncogênicas c-pim-1 , Tiazolidinas , Humanos , Animais , Camundongos , Citocinas , Antineoplásicos/farmacologia , Imunoterapia , Proliferação de Células , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia
2.
Semin Cancer Biol ; 78: 78-89, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33626407

RESUMO

Metastatic spread in breast cancer patients is the major driver of cancer-related deaths. A unique subset of cells disseminated from pre-invasive or primary tumor lesions are recognized as the main seeds for metastatic outgrowth. Disseminated cancer cells (DCCs) can migrate to distant organs and settle in a dormant state for a prolonged period until they emerge to overt metastases. Understanding the biology of breast cancer cells dissemination, dormancy and reactivation to form overt metastases has become an important focus. In this review, we discuss the recent advancements of molecular pathways involving breast cancer cell dissemination, role of chemokine-chemokine receptor networks in DCCs migration, DCCs phenotypic heterogeneity and unique genes signatures in tumor dormancy, microenvironmental regulation and specific niches that favors DCCs homing and dormancy. In addition, we also discuss recent findings relating to the role of immune response on DCC dissemination and dormancy. With recent advances in the field of immunotherapy/targeted therapy and its beneficial effects in cancer treatment, this review will focus on their impact on DCCs, reversal of stemness, tumor dormancy and metastatic relapse.


Assuntos
Neoplasias da Mama/patologia , Microambiente Tumoral , Neoplasias da Mama/terapia , Tomada de Decisão Clínica , Gerenciamento Clínico , Progressão da Doença , Feminino , Humanos , Metástase Neoplásica
3.
Ann Surg Oncol ; 30(12): 7081-7090, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37552349

RESUMO

BACKGROUND: SmartClipTM is a food and drug administration-approved, electromagnetic chip (EMC) localization system that provides three-dimensional navigation for the excision of soft tissue lesions. The purpose of this study was to analyze the accuracy and feasibility of EMC radiologic and surgical localization for benign and malignant breast lesions. PATIENTS AND METHODS: An institutional review board-approved, single institution, prospective study from October 2020 to September 2022 of 38 women undergoing breast conserving surgery with EMC localization of a single lesion > 5 mm on mammogram (MMG) or ultrasound (US) imaging. Surveys from performing breast radiologists and breast surgeons were collected after image-guided localization and surgical excision. RESULTS: Seventy-six survey responses from nine radiologists and four surgeons were received. The deployment needle and EMC were highly visible in 86.8% and 76.3% of procedures, respectively. There was no difficulty in deployment for 92.1% of procedures. The EMC was in the correct location on postdeployment MMG in 97.4% of cases. Three instances of EMC migration occurred, one 1 cm from target lesion. The targeted mass and EMC were within the surgical specimen in 97.4% of cases. On specimen radiograph, 39.5% of the EMCs were 0-1 mm from the center of the target lesion, 18.4% were within 2-4 mm, and 23.7% were within 5-10 mm. Mean operating room time for all cases was 65 min. One case required US to localize the target due to console malfunction. CONCLUSION: There was successful EMC deployment by radiologists with accurate visualization and successful surgical excision in most cases. The EnVisioTM SmartClipTM system is a reproducible and accurate localization method for benign and malignant breast lesions.


Assuntos
Neoplasias da Mama , Cirurgiões , Feminino , Humanos , Estudos Prospectivos , Mamografia , Fenômenos Eletromagnéticos , Radiologistas , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia
4.
Ann Surg Oncol ; 30(10): 6245-6253, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37458950

RESUMO

BACKGROUND: The breast cancer surgical risk calculator (BCSRc) is a prognostic tool that determines a breast cancer patient's unique risk of acute complications following each possible surgical intervention. When used in the preoperative setting, it can help to stratify patients with an increased complication risk and enhance the patient-physician informed decision-making process. The objective of this study was to externally validate the four models used in the BCSRc on a large cohort of patients who underwent breast cancer surgery. METHODS: The BCSRc was developed by using a retrospective cohort from the National Surgical Quality Improvement Program database from 2005 to 2018. Four models were built by using logistic regression methods to predict the following composite outcomes: overall, infectious, hematologic, and internal organ complications. This study obtained a new cohort of patients from the National Surgical Quality Improvement Program by utilizing participant user files from 2019 to 2020. The area under the curve, brier score, and Hosmer-Lemeshow goodness of fit test measured model performance, accuracy, and calibration, respectively. RESULTS: A total of 192,095 patients met inclusion criteria in the development of the BCSRc, and the validation cohort included 60,144 women. The area under the curve during external validation for each model was approximately 0.70. Accuracy, or Brier scores, were all between 0.04 and 0.003. Model calibration using the Hosmer-Lemeshow statistic found all p-values > 0.05. All of these model coefficients will be updated on the web-based BCSRc platform: www.breastcalc.org . CONCLUSIONS: The BCSRc continues to show excellent external-validation measures. Collectively, this prognostic tool can enhance the decision-making process, help stratify patients with an increased complication risk, and improve expectant management.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Medição de Risco/métodos , Estudos Retrospectivos , Mama , Complicações Pós-Operatórias/etiologia , Fatores de Risco
5.
Wiad Lek ; 76(12): 2543-2555, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38290016

RESUMO

Marie Sklodowska-Curie Symposia on Cancer Research and Care (MSCS-CRC) promote collaborations between cancer researchers and care providers in the United States, Canada and Central and Eastern European Countries (CEEC), to accelerate the development of new cancer therapies, advance early detection and prevention, increase cancer awareness, and improve cancer care and the quality of life of patients and their families. The third edition of MSCS-CRC, held at Roswell Park Comprehensive Cancer Center, Buffalo, NY, in September 2023, brought together 137 participants from 20 academic institutions in the US, Poland, Ukraine, Lithuania, Croatia and Hungary, together with 16 biotech and pharma entities. The key areas of collaborative opportunity identified during the meeting are a) creating of a database of available collaborative projects in the areas of early-phase clinical trials, preclinical development, and identification of early biomarkers; b) promoting awareness of cancer risks and efforts at cancer prevention; c) laboratory and clinical training; and d) sharing experience in cost-effective delivery of cancer care and improving the quality of life of cancer patients and their families. Examples of ongoing international collaborations in the above areas were discussed. Participation of the representatives of the Warsaw-based Medical Research Agency, National Cancer Institute (NCI) of the United States, National Cancer Research Institutes of Poland and Lithuania, New York State Empire State Development, Ministry of Health of Ukraine and Translational Research Cancer Center Consortium of 13 cancer centers from the US and Canada, facilitated the discussion of available governmental and non-governmental funding initiatives in the above areas.


Assuntos
Pesquisa Biomédica , Neoplasias , Humanos , Estados Unidos , New York , Qualidade de Vida , Neoplasias/terapia , Polônia
6.
Breast Cancer Res Treat ; 191(1): 209-217, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34669082

RESUMO

PURPOSE: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin. METHODS: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method. RESULTS: A total of 959 patients were identified including melanoma (31%), NSCLC (51%), and BC (18%). Patients with BC were younger at BM diagnosis (median age: 57) than NSCLC (65) and melanoma patients (62, p < 0.0001). Breast cancer patients were more likely to present with at least 5 BM (27%) than NSCLC (14%) and melanoma (13%), leptomeningeal disease (23%, 6%, and 6%, p = 0.0004) and receive whole brain radiation therapy (WBRT) (58%, 37%, and 22%, p < 0.0001). There were no differences in surgical resection (24%, 24%, and 29%, p = 0.166). Median OS was shorter for BC patients (9.9, 10.3, and 13.7 months, p = 0.0006). CONCLUSION: Breast cancer patients were more likely to be younger, present with advanced disease, require WBRT, and have poorer OS than NSCLC and melanoma patients. Further investigation is needed to determine which BC patients are at sufficient risk for brain MRI screening.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Encéfalo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/epidemiologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Melanoma/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
J Neurooncol ; 157(2): 249-269, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35244835

RESUMO

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at a particularly high risk of breast cancer brain metastasis (BCBM) and leptomeningeal disease (LMD). Improvements in systemic therapy have translated to improved survival for patients with HER2-positive BCBM and LMD. However, the optimal management of these cases is rapidly evolving and requires a multidisciplinary approach. Herein, a team of radiation oncologists, medical oncologists, neuro-oncologists, and breast surgeon created a review of the evolving management of HER2-positive BCBM and LMD. We assess the epidemiology, diagnosis, and evolving treatment options for patients with HER2-positive BCBM and LMD, as well as the ongoing prospective clinical trials enrolling these patients. The management of HER2-positive BCBM and LMD represents an increasingly common challenge that involves the coordination of local and systemic therapy. Advances in systemic therapy have resulted in an improved prognosis, and promising targeted therapies currently under prospective investigation have the potential to further benefit these patients.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Neoplasias Meníngeas , Neoplasias Encefálicas/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Neoplasias Meníngeas/terapia , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo
8.
Mol Ther ; 29(4): 1541-1556, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33412308

RESUMO

HER2 breast cancer (BC) remains a significant problem in patients with locally advanced or metastatic BC. We investigated the relationship between T helper 1 (Th1) immune response and the proteasomal degradation pathway (PDP), in HER2-sensitive and -resistant cells. HER2 overexpression is partially maintained because E3 ubiquitin ligase Cullin5 (CUL5), which degrades HER2, is frequently mutated or underexpressed, while the client-protective co-chaperones cell division cycle 37 (Cdc37) and heat shock protein 90 (Hsp90) are increased translating to diminished survival. The Th1 cytokine interferon (IFN)-γ caused increased CUL5 expression and marked dissociation of both Cdc37 and Hsp90 from HER2, causing significant surface loss of HER2, diminished growth, and induction of tumor senescence. In HER2-resistant mammary carcinoma, either IFN-γ or Th1-polarizing anti-HER2 vaccination, when administered with anti-HER2 antibodies, demonstrated increased intratumor CUL5 expression, decreased surface HER2, and tumor senescence with significant therapeutic activity. IFN-γ synergized with multiple HER2-targeted agents to decrease surface HER2 expression, resulting in decreased tumor growth. These data suggest a novel function of IFN-γ that regulates HER2 through the PDP pathway and provides an opportunity to impact HER2 responses through anti-tumor immunity.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proteínas Culina/genética , Interferon gama/genética , Receptor ErbB-2/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Senescência Celular/genética , Senescência Celular/imunologia , Chaperoninas/genética , Proteínas Culina/imunologia , Citocinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Interferon gama/imunologia , Proteólise , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Células Th1/efeitos dos fármacos , Células Th1/metabolismo , Vacinação
9.
Ann Surg Oncol ; 28(9): 5121-5131, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33616770

RESUMO

BACKGROUND: Prognostic tools, such as risk calculators, improve the patient-physician informed decision-making process. These tools are limited for breast cancer patients when assessing surgical complication risk preoperatively. OBJECTIVE: In this study, we aimed to assess predictors associated with acute postoperative complications for breast cancer patients and then develop a predictive model that calculates a complication probability using patient risk factors. METHODS: We performed a retrospective cohort study using the National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2017. Women diagnosed with ductal carcinoma in situ or invasive breast cancer who underwent either breast conservation or mastectomy procedures were included in this predictive modeling scheme. Four models were built using logistic regression methods to predict the following composite outcomes: overall, infectious, hematologic, and internal organ complications. Model performance, accuracy and calibration measures during internal/external validation included area under the curve, Brier score, and Hosmer-Lemeshow statistic, respectively. RESULTS: A total of 163,613 women met the inclusion criteria. The area under the curve for each model was as follows: overall, 0.70; infectious, 0.67; hematologic, 0.84; and internal organ, 0.74. Brier scores were all between 0.04 and 0.003. Model calibration using the Hosmer-Lemeshow statistic found all p-values to be > 0.05. Using model coefficients, individualized risk can be calculated on the web-based Breast Cancer Surgery Risk Calculator (BCSRc) platform ( www.breastcalc.org ). CONCLUSION: We developed an internally and externally validated risk calculator that estimates a breast cancer patient's unique risk of acute complications following each surgical intervention. Preoperative use of the BCSRc can potentially help stratify patients with an increased complication risk and improve expectations during the decision-making process.


Assuntos
Neoplasias da Mama , Mama , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
10.
BMC Cancer ; 21(1): 552, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992087

RESUMO

BACKGROUND: Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). METHODS: Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. RESULTS: Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR-/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15-24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24-30 Gy) in a median of 5 fractions (range: 3-5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. CONCLUSIONS: In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.


Assuntos
Neoplasias Encefálicas/terapia , Neoplasias da Mama/patologia , Capecitabina/efeitos adversos , Quimiorradioterapia/métodos , Radiocirurgia/efeitos adversos , Adulto , Idoso , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Capecitabina/administração & dosagem , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/etiologia , Estadiamento de Neoplasias , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Radiocirurgia/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
11.
BMC Cancer ; 21(1): 223, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663447

RESUMO

BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14-24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis. CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/terapia , Radiocirurgia , Receptor ErbB-2/análise , Ado-Trastuzumab Emtansina/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Necrose , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica
12.
J Neurooncol ; 152(3): 591-601, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33742358

RESUMO

PURPOSE: We investigated the prognostic ability of tumor subtype for patients with breast cancer brain metastases (BCBM) treated with stereotactic radiation (SRT). METHODS: This is a retrospective review of 181 patients who underwent SRT to 664 BCBM from 2004 to 2019. Patients were stratified by subtype: hormone receptor (HR)-positive, HER2-negative (HR+/HER2-), HR-positive, HER2-positive (HR+/HER2+), HR-negative, HER2-positive (HR-/HER2+), and triple negative (TN). The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of SRT. Multivariate analysis (MVA) was conducted using the Cox proportional hazards model. RESULTS: Median follow up from SRT was 11.4 months. Of the 181 patients, 47 (26%) were HR+/HER2+, 30 (17%) were HR-/HER2+, 60 (33%) were HR+/HER2-, and 44 (24%) were TN. Of the 664 BCBMs, 534 (80%) received single fraction stereotactic radiosurgery (SRS) with a median dose of 21 Gy (range 12-24 Gy), and 130 (20%) received fractionated stereotactic radiation therapy (FSRT), with a median dose of 25 Gy (range 12.5-35 Gy) delivered in 3 to 5 fractions. One-year LC was 90%. Two-year DIC was 35%, 23%, 27%, and 16% (log rank, p = 0.0003) and 2-year OS was 54%, 47%, 24%, and 12% (log rank, p < 0.0001) for HR+/HER2+, HR-/HER2+, HR+/HER2-, and TN subtypes, respectively. On MVA, the TN subtype predicted for inferior DIC (HR 1.62, 95% CI 1.00-2.60, p = 0.049). The modified breast-Graded Prognostic Assessment (GPA) significantly predicted DIC and OS (both p < 0.001). CONCLUSIONS: Subtype is prognostic for OS and DIC for patients with BCBM treated with SRT.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Radiocirurgia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias da Mama/radioterapia , Feminino , Humanos , Estudos Retrospectivos
13.
Breast Cancer Res Treat ; 180(2): 279-300, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32030570

RESUMO

PURPOSE: Breast cancer brain metastases (BCBM) are becoming an increasingly common diagnosis due to improved systemic control and more routine surveillance imaging. Treatment continues to require a multidisciplinary approach managing systemic and intracranial disease burden. Although, improvements have been made in the diagnosis and management of BCBM, brain metastasis patients continue to pose a challenge for practitioners. METHODS: In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in the treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of BCBM. RESULTS: We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, surgical, and radiotherapy treatment modalities), and treatment response evaluation for BCBM. Furthermore, we discuss the ongoing prospective trials enrolling BCBM patients and their biologic rationale. CONCLUSIONS: BCBM management is an increasing clinical concern. Multidisciplinary management combining the strengths of surgical, systemic, and radiation treatment modalities with prospective trials incorporating knowledge from the basic and translational sciences will ultimately lead to improved clinical outcomes for BCBM patients.


Assuntos
Neoplasias Encefálicas/terapia , Neoplasias da Mama/terapia , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Feminino , Humanos , Resultado do Tratamento
14.
Breast Cancer Res Treat ; 177(2): 277-294, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31209686

RESUMO

PURPOSE: Leptomeningeal disease (LMD) is an advanced metastatic disease presentation portending a poor prognosis with minimal treatment options. The advent and widespread use of new systemic therapies for metastatic breast cancer has improved systemic disease control and extended survival; however, as patients live longer, the rates of breast cancer LMD are increasing. METHODS: In this review, a group of medical oncologists, radiation oncologists, radiologists, breast surgeons, and neurosurgeons specializing in treatment of breast cancer reviewed the available published literature and compiled a comprehensive review on the current state of breast cancer LMD. RESULTS: We discuss the pathogenesis, epidemiology, diagnosis, treatment options (including systemic, intrathecal, surgical, and radiotherapy treatment modalities), and treatment response evaluation specific to breast cancer patients. Furthermore, we discuss the controversies within this unique clinical setting and identify potential clinical opportunities to improve upon the diagnosis, treatment, and treatment response evaluation in the management of breast LMD. CONCLUSIONS: We recognize the shortcomings in our current understanding of the disease and explore the future role of genomic/molecular disease characterization, technological innovations, and ongoing clinical trials attempting to improve the prognosis for this advanced disease state.


Assuntos
Doenças Mamárias/patologia , Carcinomatose Meníngea/secundário , Carcinomatose Meníngea/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Mamárias/diagnóstico , Doenças Mamárias/epidemiologia , Terapia Combinada , Diagnóstico por Imagem , Gerenciamento Clínico , Feminino , Humanos , Injeções Espinhais , Carcinomatose Meníngea/diagnóstico , Carcinomatose Meníngea/epidemiologia , Terapia de Alvo Molecular , Cuidados Paliativos , Padrões de Prática Médica , Prognóstico , Resultado do Tratamento
15.
Breast Cancer Res Treat ; 175(3): 781-788, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30859348

RESUMO

PURPOSE: Leptomeningeal disease is a rare presentation of advanced metastatic breast cancer. The purpose of this study was to evaluate craniospinal progression between intrathecal (IT) trastuzumab, IT chemotherapy, and whole brain radiation therapy (WBRT) in leptomeningeal disease. METHODS: A total of 56 patients were identified with breast cancer leptomeningeal disease at our institution treated with IT trastuzumab (n = 18; 32%), single-agent IT chemotherapy (methotrexate n = 14 or thiotepa n = 1; 27%), or WBRT alone (n = 23; 41%). Patients were treated beginning November 2012 and followed until November 2018. RESULTS: Median time from breast cancer diagnosis to development of leptomeningeal disease was 4.3 years. There were no significant differences noted between IT trastuzumab, IT chemotherapy, or WBRT groups in age (p = 0.4), Karnofsky Performance Status (KPS) (p = 0.07), or receipt of systemic therapy at time of leptomeningeal disease treatment (p = 0.47). Median follow-up of patients from leptomeningeal diagnosis was 5 months (range 0.2-81.1 months). Significant differences were noted in Kaplan-Meier (KM) craniospinal progression-free survival (CS-PFS) with 6-month rates of 44%, 18%, and 26% (p = 0.04) between IT trastuzumab, IT chemotherapy, and WBRT, respectively. Craniospinal control > 10 months was achieved in four patients treated with IT trastuzumab. Twelve-month KM OS rates were 54%, 10%, and 19% (p = 0.01) between IT trastuzumab, IT chemotherapy, and WBRT groups, respectively. IT therapy was adequately tolerated with three patients undergoing treatment-related hospitalizations. CONCLUSIONS: In our institutional series, significant differences were noted in CS-PFS and OS by treatment modality. IT trastuzumab should be considered in the management HER2+ breast leptomeningeal disease.


Assuntos
Neoplasias da Mama/terapia , Irradiação Craniana/métodos , Tratamento Farmacológico/métodos , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/terapia , Trastuzumab/administração & dosagem , Adulto , Idoso , Feminino , Hospitalização , Humanos , Injeções Espinhais , Avaliação de Estado de Karnofsky , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Tiotepa/administração & dosagem , Tiotepa/uso terapêutico , Trastuzumab/uso terapêutico , Resultado do Tratamento
16.
Ann Surg Oncol ; 25(10): 2852-2857, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30014455

RESUMO

BACKGROUND: Although immunotherapy is making rapid inroads as a major treatment method for melanoma, lung, bladder, and hereditary colon cancer, breast cancer (BC) remains one of the tumors yet to experience the cellular immunology explosion despite the fact that heavy lymphocyte responses in breast tumors improve response to therapy and can predict for long-term survival. RESULTS: Immunotherapies in the form of monoclonal antibodies such as trastuzumab and pertuzumab have had an impact on HER2-positive breast cancer (HER2+BC) treatment through antibody-dependent cellular cytotoxicity. Current evidence suggests that checkpoint inhibitors and other cellular therapies are at the doorstep of improving outcomes in triple-negative BC (TNBC) and HER2+BC, especially when combined with standard therapies. CONCLUSIONS: Although this approach has benefitted small numbers of patients to date, numerous clinical trials are underway to define the relative role immunotherapy may play in the treatment of BC.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Imunoterapia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico
19.
J Surg Oncol ; 117(4): 567-571, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29194673

RESUMO

BACKGROUND AND OBJECTIVES: Indications for sentinel lymph node (SLN) biopsy in patients with thin melanoma (≤1 mm thick) are controversial. We asked whether deep margin (DM) positivity at initial biopsy of thin melanoma is associated with SLN positivity. METHODS: Cases were identified using prospectively maintained databases at two melanoma centers. Patients who had undergone SLN biopsy for melanoma ≤1 mm were included. DM status was assessed for association with SLN metastasis in univariate and multivariate analyses. RESULTS: 1413 cases were identified, but only 1129 with known DM status were included. 39% of patients had a positive DM on original biopsy. DM-positive and DM-negative patients did not differ significantly in primary thickness, ulceration, or mitotic activity. DM-positive and DM-negative patients had similar incidence of SLN metastasis (5.7% vs 3.5%; P = 0.07). Positive DM was not associated with SLN metastasis on univariate analysis (OR 1.69, 95% CI: 0.95-3.00, P = 0.07) or on multivariate analysis adjusted for Breslow depth, Clark level, mitotic rate, and ulceration (OR = 1.59, 95% CI: 0.89-2.85; P = 0.12). CONCLUSIONS: For patients with thin melanoma, a positive DM on initial biopsy is not associated with risk of SLN metastasis, so DM positivity should not be considered an indication for SLN staging in an otherwise low-risk patient.


Assuntos
Melanoma/patologia , Melanoma/cirurgia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Bases de Dados Factuais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos
20.
J Surg Oncol ; 117(4): 558-566, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29127721

RESUMO

BACKGROUND AND OBJECTIVES: The impact of preoperative magnetic resonance imaging (pMRI) and cavity shave margins (CSM) on re-excision rate (RR) in DCIS is unclear. We investigated whether either modality was associated with RR in DCIS. METHODS: This is a single-institution retrospective study of 295 women undergoing breast conservation surgery for pure DCIS (2010-2013). CSM were the systematic resection of 4-6 margins during lumpectomy whereas selective shave margins (SSM) were the selective resection of 1-3 margins. Patient demographics and clinical characteristics were abstracted. RR was analyzed according to the use of pMRI, SSM, or CSM with respect to three high-volume breast surgeons at our institution. RESULTS: RR was not associated with the use of pMRI (P = 0.87). Any shave margins (P = 0.05), DCIS size (P < 0.001), and DCIS grade (P = 0.14) associated with a lower RR. Of our high-volume surgeons, RR was lower for Surgeon A (P = 0.02). Multivariate analyses showed larger DCIS (OR 1.35, P = 0.005) and practices specific to surgeons B (OR 3.23, P = 0.04) and C (OR 3.57, P = 0.04) increased re-excision odds. CONCLUSIONS: SSM/CSM and pMRI use varied among surgeons. Our results suggested the routine use of CSM, not pMRI, could lower re-excision rate, which highlighted a quality improvement opportunity at our institution.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos
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