Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.445
Filtrar
1.
J Surg Oncol ; 123(5): 1206-1214, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33577715

RESUMO

PURPOSE: To evaluate the acceptability and impact of 3D-printed breast models (3D-BMs) on treatment-related decisional conflict (DC) of breast cancer patients. METHODS: Patients with breast cancer were accrued in a prospective institutional review board-approved trial. All patients underwent contrast-enhanced breast magnetic resonance imaging (MRI). A personalized 3D-BM was derived from MRI. DC was evaluated pre- and post-3D-BM review. 3D-BM acceptability was assessed post-3D-BM review. RESULTS: DC surveys before and after 3D-BM review and 3D-BM acceptability surveys were completed by 25 patients. 3D-BM were generated in two patients with bilateral breast cancer. The mean patient age was 48.8 years (28-72). The tumor stage was Tis (7), 1 (8), 2 (8), and 3 (4). The nodal staging was 0 (19), 1 (7), and 3 (1). Tumors were unifocal (15), multifocal (8), or multicentric (4). Patients underwent mastectomy (13) and segmental mastectomy (14) with (20) or without (7) oncoplastic intervention. Neoadjuvant therapy was given to seven patients. Patients rated the acceptability of the 3D-BM as good/excellent in understanding their condition (24/24), understanding disease size (25/25), 3D-BM detail (22/25), understanding their surgical options (24/25), encouraging to ask questions (23/25), 3D-BM size (24/25), and impartial to surgical options (17/24). There was a significant reduction in the overall DC post-3D-BM review, indicating patients became more assured of their treatment choice (p = 0.002). Reduction post-3D-BM review was also observed in the uncertainty (p = 0.012), feeling informed about options (p = 0.005), clarity about values (p = 0.032), and effective (p = 0.002) Decisional Conflict Scale subscales. CONCLUSIONS: 3D-BMs are an acceptable tool to decrease DC in breast cancer patients.


Assuntos
Neoplasias da Mama/cirurgia , Técnicas de Apoio para a Decisão , Conhecimentos, Atitudes e Prática em Saúde , Imagem por Ressonância Magnética/métodos , Mastectomia/estatística & dados numéricos , Participação do Paciente , Impressão Tridimensional/instrumentação , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/psicologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/psicologia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/psicologia , Carcinoma Lobular/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Mastectomia/psicologia , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
2.
J Cancer Res Clin Oncol ; 147(4): 1041-1048, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33471187

RESUMO

PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. CONCLUSION: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
3.
BMJ Case Rep ; 14(1)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468635

RESUMO

The diagnosis via core needle biopsy of concurrent ductal carcinoma in situ and lobular carcinoma in situ within an enlarging previously biopsied benign fibroadenoma in women in their 40s is rare. Several case reports have described the occurrence of malignant changes within fibroadenomas, usually as an incidental finding following excision, and few reports have documented the transition of a fibroadenoma to malignancy. The current case report emphasises the importance of re-biopsying enlarging fibroadenomas, even with otherwise maintained benign appearing features on imaging, in women in their 40s, in order to exclude the possibility of malignancy.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/patologia , Fibroadenoma/patologia , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/terapia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/terapia , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade
4.
J Surg Res ; 257: 144-152, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32828998

RESUMO

BACKGROUND: Invasive lobular carcinoma (ILC) has unique histologic growth pattern. Few studies have focused on the value of breast magnetic resonance imaging (MRI) specifically for ILC. We hypothesized that MRI adds value to the diagnostic workup in ILC by better defining the extent of disease and identifying additional foci of malignancy, which can change the surgical plan. MATERIALS AND METHODS: This was a single-institution retrospective review of women diagnosed with ILC from 1/2012 to 7/2019 who underwent preoperative MRI. Patient, tumor characteristics, and initial surgical plan were reviewed. MRI had added value if ILC size correlated best to final pathologic size or if additional malignancy was identified. MRI was considered harmful if additional biopsies were benign or if the size was overestimated. RESULTS: ILC was identified in 166 breasts in 165 women. Original surgical plan was for lumpectomy in 86 (52%), mastectomy in 49 (30%), and undecided in 31 (18%). MRI changed the plan in 25 (19%) with 24 (96%) changing from lumpectomy to mastectomy. Additional biopsy was performed in 28% after MRI, the majority (n = 41, 72%) were benign or high risk and 16 (28%) identified additional malignancy. MRI was not a better size estimate than mammogram/ultrasound. Re-excision rate after lumpectomy was 6.8% (5/73). MRI added value in 48 (28.9%) and was harmful in 48 (28.9%). CONCLUSIONS: Using breast MRI in the diagnostic workup of ILC has both positive and negative implications on surgical treatment planning. A shared decision-making conversation is warranted before proceeding with MRI to maximize value and minimize harms associated with this diagnostic tool.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/cirurgia , Imagem por Ressonância Magnética , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos
5.
Radiol Clin North Am ; 59(1): 29-40, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33222998

RESUMO

High-risk breast lesions (HRLs) are a group of heterogeneous lesions that can be associated with a synchronous or adjacent breast cancer and that confer an elevated lifetime risk of breast cancer. Management of HRLs after core needle biopsy may include close imaging and clinical follow-up or excisional biopsy to evaluate for cancer. This article reviews histologic features and clinical presentation of each of the HRLs, current evidence with regard to management, and guidelines from the American Society of Breast Surgeons and National Comprehensive Cancer Network. In addition, imaging surveillance and risk-reduction strategies for women with HRLs are discussed.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Mamografia/métodos , Biópsia com Agulha de Grande Calibre , Mama/diagnóstico por imagem , Mama/patologia , Feminino , Humanos , Medição de Risco
6.
Am J Surg ; 221(1): 32-36, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32622509

RESUMO

BACKGROUND: The safety of breast conservation therapy (BCT) has not been demonstrated in large ILC tumors, potentially contributing to the higher mastectomy rates seen in ILC. METHODS: We queried a prospectively maintained database to identify patients with ILC measuring ≥4 cm and evaluated difference in recurrence free survival (RFS) between those treated with BCT versus mastectomy using a multivariate model. RESULTS: Of 180 patients, 30 (16.7%) underwent BCT and 150 (83.3%) underwent mastectomy. Patients undergoing mastectomy were younger (56.6 vs. 64.3 years, p = 0.003) and had larger tumors (7.2 vs. 5.4 cm, p < 0.001). While tumor size, nodal stage, receptor subtype, and margin status were significantly associated with RFS, there was no difference in RFS at 5 (p = 0.88) or 10 (p = 0.65) years for individuals undergoing BCT versus mastectomy. CONCLUSIONS: For patients with ILC ≥4 cm, BCT provides similar tumor control as mastectomy, provided that negative margins are achieved.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Lobular/cirurgia , Mastectomia Segmentar , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Tumoral
7.
Medicine (Baltimore) ; 99(43): e22807, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120801

RESUMO

We aimed to establish and validate a nomogram for predicting the disease-specific survival of invasive lobular carcinoma (ILC) patients.The Surveillance, Epidemiology, and End Results program database was used to identify ILC from 2010 to 2015, in which the data was extracted from 18 registries in the US. Multivariate Cox regression analysis was performed to identify independent prognostic factors and a nomogram was constructed to predict the 3-year and 5-year survival rates of ILC patients based on Cox regression. Predictive values were compared between the new model and the American Joint Committee on Cancer staging system using the concordance index, calibration plots, integrated discrimination improvement, net reclassification improvement, and decision-curve analyses.In total, 4155 patients were identified. After multivariate Cox regression analysis, nomogram was established based on a new model containing the predictive variables of age, the primary tumor site, histology grade, American Joint Committee on Cancer TNM (tumor node metastasis) stages II, III, and IV, breast cancer subtype, therapy modality (surgery and chemotherapy). The concordance index for the training and validation cohorts were higher for the new model (0.781 and 0.832, respectively) than for the old model (0.733 and 0.779). The new model had good performance in the calibration plots. Net reclassification improvement and integrated discrimination improvement were also improved. Finally, decision-curve analyses demonstrated that the nomogram was clinically useful.We have developed a reliable nomogram for determining the prognosis and treatment outcomes of ILC. The new model facilitates the choosing of superior medical examinations and the optimizing of therapeutic regimens with cooperation among oncologists.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Nomogramas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Análise de Regressão , Reprodutibilidade dos Testes , Fatores Sexuais , Fatores Socioeconômicos , Análise de Sobrevida
8.
Medicine (Baltimore) ; 99(31): e21211, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756099

RESUMO

RATIONALE: Within a rapidly expanding therapeutic armamentarium, the combination of everolimus (Eve) plus exemestane (Exe) utility needs to be reinstated in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). PATIENT CONCERNS: We herein report on a patient affected by HR+ HER2- MBC treated with radical surgery after neoadjuvant chemotherapy, who relapsed early on adjuvant tamoxifen, progressed rapidly on first line anastrozole, and failed treatment with third line capecitabine. DIAGNOSES: Metastatic luminal breast cancer progressed under standard endocrine therapy and chemotherapy. INTERVENTIONS: Third line with Eve plus Exe was given after chemotherapy. OUTCOMES: Patient experienced a 5-year progression free interval. LESSONS: Eve plus Exe remains a valid option in HR+HER2- MBC.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Everolimo/administração & dosagem , Everolimo/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Pré-Menopausa , Intervalo Livre de Progressão
9.
J Exp Clin Cancer Res ; 39(1): 171, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854728

RESUMO

The Covid-19 pandemic has challenged hard the national health systems worldwide. According to the national policy issued in March 2020 in response to the evolving Covid-19 pandemic, several hospitals were re-configured as Covid-19 centers and elective surgery procedures were rescheduled according to the most recent recommendations. In addition, Covid-19 protected cancer hubs were established, including the Regina Elena National Cancer Institute of Rome, Central Italy. At our Institute, the Breast Surgery Department continued working under the sign of a multidisciplinary approach. The number of professional figures involved in case evaluation was reduced to a minimum and interactions took place in the full respect of the required safety measures. Treatments for benign disease, pure prophylactic surgery and elective reconstructive procedures were all postponed and priority was assigned to the histologically-proven malignant breast tumors and highly suspicious lesions. From March 15th though April 30th 2020, we treated a total of 79 patients. This number is fully consistent with the average quantitative standards reached by our Department under ordinary circumstances. Patients were mostly discharged the day after surgery and none was readmitted due to surgery-related late complications. More generally, post-operative complications rates were unexpectedly low, particularly in light of the relatively high number of reconstructive procedures performed in this emergency situation. A strict follow up was performed based on the close contact with the surgical staff by telephone, messaging apps and telemedicine.Patients ascertainment for their Covid-19 status prior to hospital admission and hospital discharge allowed to maintain the "no-Covid-19" status at our Institution. In addition, during the aforementioned time window, none of the care providers developed SARS-CoV-2 infection or disease, as shown by the results of anti-SARS-CoV-2 immunoglobulin M and G profiling. In conclusions, elective breast cancer surgery procedures were successfully performed in a lockdown situation due to a novel viral pandemic. The well-coordinated regional and hospital efforts in terms of medical resource re-allocation and definition of clinical priorities allowed to maintain high quality standards of breast cancer care while ensuring safety to the cancer patients and care providers involved.


Assuntos
Betacoronavirus/isolamento & purificação , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Infecções por Coronavirus/prevenção & controle , Mastectomia/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Padrões de Prática Médica/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/virologia , Carcinoma Lobular/patologia , Carcinoma Lobular/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
10.
Korean J Radiol ; 21(8): 946-954, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32677379

RESUMO

OBJECTIVE: To investigate preoperative magnetic resonance imaging (MRI) findings associated with resection margin status in patients with invasive lobular carcinoma (ILC) who underwent breast-conserving surgery. MATERIALS AND METHODS: One hundred and one patients with ILC who underwent preoperative MRI were included. MRI (tumor size, multifocality, type of enhancing lesion, distribution of non-mass enhancement [NME], and degree of background parenchymal enhancement) and clinicopathological features (age, pathologic tumor size, presence of ductal carcinoma in situ [DCIS] or lobular carcinoma in situ, presence of lymph node metastases, and estrogen receptor/progesterone receptor/human epidermal growth factor receptor type 2 status) were analyzed. A positive resection margin was defined as the presence of invasive cancer or DCIS at the inked surface. Logistic regression analysis was performed to determine pre- and postoperative variables associated with positive resection margins. RESULTS: Among the 101 patients, 21 (20.8%) showed positive resection margins. In the univariable analysis, NME, multifocality, axillary lymph node metastasis, and pathologic tumor size were associated with positive resection margins. With respect to preoperative MRI findings, multifocality (odds ratio [OR] = 3.977, p = 0.009) and NME (OR = 2.741, p = 0.063) were associated with positive resection margins in the multivariable analysis, although NME showed borderline significance. CONCLUSION: In patients with ILC, multifocality and the presence of NME on preoperative breast MRI were associated with positive resection margins.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Lobular/diagnóstico por imagem , Margens de Excisão , Mastectomia Segmentar/métodos , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Feminino , Humanos , Metástase Linfática/patologia , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
S Afr Med J ; 110(4): 296-301, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32657741

RESUMO

BACKGROUND: There has been no comprehensive study determining the financial burden of breast cancer in the South African (SA) public sector. OBJECTIVES: To develop a method to determine the cost of breast cancer treatment with chemotherapy per episode of care and to quantify the associated costs relating to chemotherapy at Groote Schuur Hospital (GSH), a government hospital in SA. These costs included costs associated with the management of adverse events arising from chemotherapy. METHODS: Retrospective patient-level data were collected for 200 patients from electronic databases and patient folders between 2013 and 2015. Direct medical costs were determined from the health funder's perspective. The information collected was categorised into the following cost components: chemotherapy medicines, support medicines, administration of chemotherapy, laboratory tests, radiology scans and imaging, doctor consultations and adverse events. Time-and-motion studies were conducted on a set of new patients and the data obtained were used for the study sample of 200 patients. All the above costs were used to determine the cost of chemotherapy per episode of care. The episode of care was defined as the care provided from 2 months prior to the date of commencing chemotherapy (pre-chemotherapy phase), during chemotherapy (treatment phase) and until 6 months after the date when the last cycle of chemotherapy was administered (follow-up phase). RESULTS: A method was developed to determine the episode-of-care costs for breast cancer at GSH. The total direct medical cost for treatment of breast cancer at GSH for 200 patients was ZAR3 154 877, and the average episode-of-care cost per patient was ZAR15 774. The average cost of management of adverse events arising from the various treatment modalities was ZAR13 133 per patient. It was found that the cost of treating a patient with adverse events was 1.8 times higher than the cost of treating a patient without adverse events. Of the patients, 86.5% managed to complete their prescribed chemotherapy treatment cycles, and the average cost of treatment of these patients was 1.3 times more than the average cost for patients who could not complete their treatment, based on the number of treatment cycles received. CONCLUSION: A comprehensive method to determine the costs associated with breast cancer management per episode of care was developed, and costs were quantified at GSH according to the treatment protocol used at the hospital.


Assuntos
Antineoplásicos/economia , Carcinoma de Mama in situ/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitais Públicos/economia , Adulto , Idoso , Carcinoma de Mama in situ/economia , Carcinoma de Mama in situ/patologia , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/economia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/economia , Carcinoma Lobular/patologia , Quimioterapia Adjuvante/economia , Técnicas de Laboratório Clínico/economia , Diagnóstico por Imagem/economia , Custos de Medicamentos/estatística & dados numéricos , Cuidado Periódico , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/economia , Cuidados Paliativos/economia , Honorários por Prescrição de Medicamentos/estatística & dados numéricos , Encaminhamento e Consulta/economia , Estudos Retrospectivos , África do Sul , Estudos de Tempo e Movimento , Adulto Jovem
12.
Breast Cancer Res ; 22(1): 76, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665033

RESUMO

BACKGROUND: Early luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients. METHODS: Our study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5-2 cm without lymph node metastasis) with metastatic recurrence ("cases") and corresponding "controls" (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF). RESULTS: We found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that "cases" are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4+ T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients. CONCLUSIONS: This study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.


Assuntos
Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Fibroblastos Associados a Câncer/imunologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/imunologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Microambiente Tumoral/imunologia
13.
Sci Rep ; 10(1): 10936, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616912

RESUMO

Response to Neoadjuvant chemotherapy (NAC) has demonstrated a high correlation to survival in locally advanced breast cancer (LABC) patients. An early prediction of responsiveness to NAC could facilitate treatment adjustments on an individual patient basis that would be expected to improve treatment outcomes and patient survival. This study investigated, for the first time, the efficacy of quantitative computed tomography (qCT) parametric imaging to characterize intra-tumour heterogeneity and its application in predicting tumour response to NAC in LABC patients. Textural analyses were performed on CT images acquired from 72 patients before the start of chemotherapy to determine quantitative features of intra-tumour heterogeneity. The best feature subset for response prediction was selected through a sequential feature selection with bootstrap 0.632 + area under the receiver operating characteristic (ROC) curve ([Formula: see text]) as a performance criterion. Several classifiers were evaluated for response prediction using the selected feature subset. Amongst the applied classifiers an Adaboost decision tree provided the best results with cross-validated [Formula: see text], accuracy, sensitivity and specificity of 0.89, 84%, 80% and 88%, respectively. The promising results obtained in this study demonstrate the potential of the proposed biomarkers to be used as predictors of LABC tumour response to NAC prior to the start of treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Aprendizado de Máquina , Terapia Neoadjuvante/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/tratamento farmacológico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Adulto Jovem
14.
PLoS One ; 15(7): e0235790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697770

RESUMO

Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma Lobular/patologia , Receptores Androgênicos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
16.
Breast Cancer Res ; 22(1): 69, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576238

RESUMO

BACKGROUND: In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. METHODS: Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. RESULTS: In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups. CONCLUSIONS: Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.


Assuntos
Antígeno B7-H1/biossíntese , Neoplasias da Mama/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/imunologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Terapia Combinada , Aprovação de Drogas , Feminino , Seguimentos , Humanos , Imuno-Histoquímica/métodos , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos , United States Food and Drug Administration
17.
Breast Cancer Res ; 22(1): 68, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576280

RESUMO

BACKGROUND: Breast cancer is a highly heterogeneous disease characterized by multiple histologic and molecular subtypes. While a myriad of breast cancer cell lines have been developed over the past 60 years, estrogen receptor alpha (ER)+ disease and some mutations associated with this subtype remain underrepresented. Here we describe six breast cancer cell lines derived from patient-derived xenografts (PDX) and their general characteristics. METHODS: Established breast cancer PDX were processed into cell suspensions and placed into standard 2D cell culture; six emerged into long-term passageable cell lines. Cell lines were assessed for protein expression of common luminal, basal, and mesenchymal markers, growth assessed in response to estrogens and endocrine therapies, and RNA-seq and oncogenomics testing performed to compare relative transcript levels and identify putative oncogenic drivers. RESULTS: Three cell lines express ER and two are also progesterone receptor (PR) positive; PAM50 subtyping identified one line as luminal A. One of the ER+PR+ lines harbors a D538G mutation in the gene for ER (ESR1), providing a natural model that contains this endocrine-resistant genotype. The third ER+PR-/low cell line has mucinous features, a rare histologic type of breast cancer. The three other lines are ER- and represent two basal-like and a mixed ductal/lobular breast cancer. The cell lines show varied responses to tamoxifen and fulvestrant, and three were demonstrated to regrow tumors in vivo. RNA sequencing confirms all cell lines are human and epithelial. Targeted oncogenomics testing confirmed the noted ESR1 mutation in addition to other mutations (i.e., PIK3CA, BRCA2, CCND1, NF1, TP53, MYC) and amplifications (i.e., FGFR1, FGFR3) frequently found in breast cancers. CONCLUSIONS: These new generation breast cancer cell lines add to the existing repository of breast cancer models, increase the number of ER+ lines, and provide a resource that can be genetically modified for studying several important clinical breast cancer features.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Linhagem Celular Tumoral , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Técnicas de Cultura de Células , Feminino , Perfilação da Expressão Gênica , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
18.
Breast Cancer Res ; 22(1): 70, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32586354

RESUMO

BACKGROUND: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival. METHODS: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed. RESULTS: Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28-77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM. CONCLUSIONS: OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Lobular/mortalidade , Neoplasias Orbitárias/secundário , Adulto , Idoso , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Orbitárias/metabolismo , Neoplasias Orbitárias/radioterapia , Prognóstico , Radioterapia de Intensidade Modulada , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
Breast Cancer Res ; 22(1): 46, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410705

RESUMO

BACKGROUND: The presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. However, the significance of TILs is less clear in luminal breast cancer. Here, we in postmenopausal patients with primary oestrogen receptor-positive (ER+), HER2 normal, operable breast cancer assessed the importance of inducing TILs during 4 months of letrozole on response in a neoadjuvant phase II study. METHODS: Participants were postmenopausal women with ER+, HER2 normal operable breast cancer assigned to 4 months of neoadjuvant letrozole. Pretreatment core biopsies and surgical specimens were assessed centrally for the percentage of TILs on haematoxylin and eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. Pathological response was assessed by the Residual Cancer Burden (RCB) index and a modified Miller-Payne grading system and was analysed according to change in TILs. RESULTS: Tumour specimens were available from 106 of the 112 patients treated per protocol. TIL concentration increased with mean 6.8 percentage point (p < 0.0001) during treatment (range - 39 to 60). An increase in TILs was significantly associated with pathological response with OR = 0.71 (95% CI 0.53-0.96; p = 0.02) per 10% absolute increase for pathological response and correspondingly OR = 0.56 (95% CI 0.40-0.78; p = 0.0007) for lower RCB index per 10% increase. CONCLUSION: Increasing TILs during letrozole was significantly associated with a poor treatment response. An increase in TILs during endocrine therapy might imply immunogenicity, and these patients could be targetable by immunotherapy. TRIAL REGISTRATION: ClinicalTrials.govNCT00908531, registered 27 May 2009.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Letrozol/uso terapêutico , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/imunologia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
20.
Breast Cancer Res ; 22(1): 49, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414408

RESUMO

BACKGROUND: Most breast cancer-associated fibroblasts (CAFs) are active and important cancer-promoting cells, with significant impact on patient prognosis. Therefore, we investigated here the role of the protein kinase ATR in breast stromal fibroblasts in the prognosis of locally advanced breast cancer patients. METHODS: We have used immunohistochemistry to assess the level of ATR in breast cancer tissues and their adjacent normal tissues. Immunoblotting as well as quantitative RT-PCR were utilized to show the role of breast cancer cells and IL-6 as well as AUF-1 in downregulating ATR in breast stromal fibroblasts. Engineered human breast tissue model was also used to show that ATR-deficient breast stromal fibroblasts enhance the growth of breast cancer cells. RESULTS: We have shown that the protein kinase ATR is downregulated in cancer cells and their neighboring CAFs in breast cancer tissues as compared to their respective adjacent normal tissues. The implication of cancer cells in ATR knockdown in CAFs has been proven in vitro by showing that breast cancer cells downregulate ATR in breast fibroblasts in an IL-6/STAT3-dependent manner and via AUF-1. In another cohort of 103 tumors from locally advanced breast cancer patients, we have shown that absence or reduced ATR expression in tumoral cells and their adjacent stromal fibroblasts is correlated with poor overall survival as well as disease-free survival. Furthermore, ATR expression in CAFs was inversely correlated with tumor recurrence and progression. CONCLUSION: ATR downregulation in breast CAFs is frequent, procarcinogenic, and correlated with poor patient survival.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/biossíntese , Neoplasias da Mama/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Recidiva Local de Neoplasia/patologia , Células Estromais/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Células Estromais/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...