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1.
Lancet ; 395(10218): 117-122, 2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31839281

RESUMO

BACKGROUND: Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period. METHODS: IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer. FINDINGS: 3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed. INTERPRETATION: This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality. FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.


Assuntos
Anastrozol/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Administração Oral , Adulto , Idoso , Anastrozol/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento , Reino Unido/epidemiologia
2.
Prostate ; 80(3): 284-290, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31860754

RESUMO

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) has a poor prognosis and is thought to be completely resistant to current therapies, including androgen deprivation therapy (ADT). However, to date, there are no data showing direct evidence of such resistance. METHODS: We retrospectively evaluated 145 patients with high-risk prostate cancer who underwent radical prostatectomy (RP) with neoadjuvant ADT between 1991 and 2005. All patient data were collected from slides prepared from needle biopsy (NB) samples of prostate tissue and RP specimens. Data were analyzed in terms of serum level of prostate specific antigen (PSA), Gleason score of NB samples, clinical T stage, the positive cancer core rate, maximum cancer extension rate, presence of Gleason pattern 5, and presence of IDC-P in both NB samples and RP specimens. RESULTS: The median initial PSA was 33.2 ng/mL (range, 2.4-296 ng/mL), and the median follow-up period was 109 months (range, 11-257 months). The preoperative median ADT period was 4 months (range, 1-20 months). IDC-P was present in 53 patients (37%) in NB samples and 65 (45%) in RP. The patients were divided into three groups based on the presence or absence of IDC-P in NB/RP samples (IDC-P-negative at biopsy: 92 cases, IDC-P-positive at biopsy with IDC-P disappearance: 15 cases, and IDC-P-positive at biopsy with IDC-P persistence: 38 cases). Overall, 28% of IDC-P-positive cases in NB samples showed the disappearance of IDC-P at RP. IDC-P persistence cases showed the poorest prognosis, while IDC-P disappearance cases had a similar prognosis to that of IDC-P-negative at biopsy cases in terms of disease-free survival, cancer-specific survival, and overall survival (P = .0018, P = .0087, and P = .0034, respectively). CONCLUSIONS: Some cases with IDC-P responded to ADT and demonstrated favorable clinical outcomes similar to those of cases without IDC-P. These findings indicate that cases with IDC-P are heterogeneous.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/cirurgia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Intraductal não Infiltrante/sangue , Carcinoma Intraductal não Infiltrante/patologia , Intervalo Livre de Doença , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos
3.
Int J Radiat Oncol Biol Phys ; 105(3): 471-472, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31540590
4.
Eur J Radiol ; 118: 114-121, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31439230

RESUMO

PURPOSE: To evaluate the radiologic and clinicopathologic factors in radiologic-pathologic discordance (false-negative results) in breast cancer patients who demonstrate radiologic complete response (rCR) in MR imaging after neoadjuvant chemotherapy (NAC). METHOD: Our institutional review board approved this retrospective study. We included 209 consecutive patients who showed rCR in MR imaging after NAC. rCR was diagnosed when the original lesion site showed no enhancement. Pathologic CR (pCR) was defined as the complete absence of both invasive cancer and ductal carcinoma in situ in the breast upon pathology. Clinicopathologic and radiologic factors affecting the radiologic-pathologic correlation were analyzed. RESULTS: pCR was noted in 108 patients (51.7%); the remaining 101 (48.3%) had residual lesion on pathology. False negative rCR findings were significantly more frequent in cases of 1 or 2 histologic grade (p = 0.001), low tumor-infiltrating lymphocytes (p = 0.004), and luminal A or B subtype (p < 0.001). Multivariate analysis of radiologic findings to identify predictors of false negative findings found calcifications in mammography (p = 0.037), multifocal multicentric lesions (p = 0.004), and non-mass enhancement in pretreatment MR imaging (p = 0.023) to be significantly associated with false-negative findings. CONCLUSIONS: Patients with calcification in mammography, multifocal multicentric lesions, and non-mass enhancement in pretreatment MR imaging are significantly associated with false-negative results who showed rCR on MR imaging after NAC. These patient populations should be interpreted with caution.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Mama/patologia , Neoplasias da Mama/patologia , Calcinose/tratamento farmacológico , Calcinose/patologia , Carcinoma Intraductal não Infiltrante/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Mamografia/métodos , Pessoa de Meia-Idade , Imagem Multimodal , Terapia Neoadjuvante/métodos , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
5.
Pak J Pharm Sci ; 32(3): 1121-1128, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278729

RESUMO

There has been a number of studies looking into an alternative mode of therapy for the treament of breast cancer via 4-hydroxytamoxifen (4-OHT) transdermal administration.This systematic review aims to compare the safety and efficacy of a transdermal 4-OHT local therapy and oral tamoxifen (oral-T) on the treatment of ductal carcinoma in situ breast cancer. Through a systematic search of health science databases, eligible trials were located and the end points assessed were Ki-67 labeling index, concentration of 4-OHT in breast adipose tissue (ng/g) and plasma (ng/ml). Revman 5.3 version was used to perfom the meta-analysis. Three trials were identified (n=103), while only two were included for meta analysis. The mean difference between the two studies included were 0.40 and -10.58. Overall the I2 value was 89.0%, (Tau2 =53.86) and the differences between the two trials were statistically significant p=0.002. The meta analysis of the randomized controlled trials showed that the use of local transdermal therapy of 4-OHT gel is more safer than oral-T. However, due to the limited number of studies, the potential use of 4-OHT topical transdermal therapy for the treatment of breast cancer could not be concluded for healthcare professionals.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/análogos & derivados , Tamoxifeno/administração & dosagem , Administração Cutânea , Administração Oral , Antineoplásicos/farmacocinética , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamoxifeno/farmacocinética , Tamoxifeno/farmacologia
6.
Ann Surg Oncol ; 26(10): 3071-3079, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342361

RESUMO

BACKGROUND: Patients with epidermal growth factor receptor 2-positive (HER2+) breast cancer and pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) may be candidates for nonoperative clinical trials if residual invasive and in situ disease are eradicated. METHODS: This study analyzed 280 patients with clinical T1-2N0-1 HER2+ breast cancer who underwent NST followed by surgical resection to determine key characteristics of patients with pCR in the breast and lymph nodes compared with those with residual disease. RESULTS: Of the 280 patients, 102 (36.4%) had pCR in the breast and lymph nodes after NST, and 50 patients (17.9%) had residual ductal carcinoma in situ (DCIS) in the breast only. For 129 patients (46.1%), DCIS was present on the pretreatment biopsy, and NST failed to eradicate the DCIS component in 64.3%. Patients with residual disease were more likely to have hormone receptor-positive (HR+) tumors than those with negative tumors (73.4% vs. 50.8%; p < 0.0001). Radiologic response (odds ratio [OR], 5.62; p = 0.002) and HR+ status (OR, 2.56; p < 0.0001) were predictive of residual disease. Combined imaging methods after NST had a sensitivity of 97.1% and a negative predictive value of 70.6% for detection of residual disease. Patients with invasive disease and DCIS shown on the pretreatment core biopsy were less likely than those without DCIS to achieve pCR in the breast (31% vs. 43%; p = 0.038). CONCLUSION: The study results delineate and identify unique characteristics associated with HER2+ breast cancers that are important in selecting patients for inclusion in clinical trials assessing nonoperative management after NST, and the low negative predictive value of imaging mandates image-guided biopsy for selection.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Linfonodos/patologia , Terapia Neoadjuvante/métodos , Neoplasia Residual/patologia , Seleção de Pacientes , Receptor ErbB-2/metabolismo , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Seguimentos , Humanos , Biópsia Guiada por Imagem/métodos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/metabolismo , Prognóstico , Estudos Prospectivos
7.
Int J Radiat Oncol Biol Phys ; 105(2): 267-274, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175905

RESUMO

PURPOSE: To report 5-year outcomes of a phase 2 trial of hypofractionated whole breast irradiation (HF-WBI) completed in 3 weeks, inclusive of a sequential boost. METHODS AND MATERIALS: Women with stage 0-IIIA breast cancer (ductal carcinoma in situ through T2N2a) were enrolled on a prospective, phase 2 trial of accelerated HF-WBI. We delivered a whole breast dose of 36.63 Gy in 11 fractions of 3.33 Gy, with an equivalent dose to the regional nodes when indicated, followed by a tumor bed boost of 13.32 Gy in 4 fractions of 3.33 Gy over a total of 15 treatment days. The primary endpoint was locoregional control; secondary endpoints included acute/late toxicity and physician-assessed and patient-reported breast cosmesis. RESULTS: Between 2009 and 2017, we enrolled 150 patients, of whom 146 received the protocol treatment. Median age was 54 years (range, 33-82) and median follow-up was 62 months. Patients with higher-risk disease comprised 59% of the cohort, including features such as young age (33% ≤50 years), positive nodes (13%), triple-negative disease (11%), and treatment with regional nodal irradiation (11%) and/or neoadjuvant/adjuvant chemotherapy (36%). Five-year estimated locoregional and distant control were 97.7% (95% confidence interval [CI], 93.0%-99.3%) and 97.9% (95% CI, 93.6%-99.3%), respectively. Five-year breast cancer-specific and overall survival were 99.2% (95% CI, 94.6%-99.9%) and 97.3% (95% CI, 91.9%-99.1%), respectively. Acute/late grade 2 and 3 toxicities were observed in 30%/10% and 1%/3% of patients, respectively. There were no grade 4 or 5 toxicities. Physicians assessed breast cosmesis as good or excellent in 95% of patients; 85% of patients self-reported slight to no difference between the treated and untreated breast. CONCLUSIONS: Our phase 2 trial offers one of the shortest courses of HF-WBI; at 5 years of follow-up there continues to be excellent locoregional control and low toxicity with favorable cosmetic outcomes in a heterogeneous cohort of patients.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/patologia , Quimioterapia Adjuvante , Intervalos de Confiança , Feminino , Humanos , Modelos Lineares , Irradiação Linfática , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Hipofracionamento da Dose de Radiação , Radiodermatite/etiologia , Planejamento da Radioterapia Assistida por Computador , Radioterapia Conformacional/efeitos adversos , Reirradiação , Fatores de Tempo , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/radioterapia
8.
PLoS One ; 14(3): e0213749, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870478

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) is used in patients with breast cancer to reduce tumor focus, metastatic risk, and patient mortality. Monitoring NAC effects is necessary to capture resistant patients and stop or change treatment. The existing methods for evaluating NAC results have some limitations. The aim of this study was to assess the tumor response at an early stage, after the first doses of the NAC, based on the variability of the backscattered ultrasound energy, and backscatter statistics. The backscatter statistics has not previously been used to monitor NAC effects. METHODS: The B-mode ultrasound images and raw radio frequency data from breast tumors were obtained using an ultrasound scanner before chemotherapy and 1 week after each NAC cycle. The study included twenty-four malignant breast cancers diagnosed in sixteen patients and qualified for neoadjuvant treatment before surgery. The shape parameter of the homodyned K distribution and integrated backscatter, along with the tumor size in the longest dimension, were determined based on ultrasound data and used as markers for NAC response. Cancer tumors were assigned to responding and non-responding groups, according to histopathological evaluation, which was a reference in assessing the utility of markers. Statistical analysis was performed to rate the ability of markers to predict the final NAC response based on data obtained after subsequent therapeutic doses. RESULTS: Statistically significant differences (p<0.05) between groups were obtained after 2, 3, 4, and 5 doses of NAC for quantitative ultrasound markers and after 5 doses for the assessment based on maximum tumor dimension. Statistical analysis showed that, after the second and third NAC courses the classification based on integrated backscatter marker was characterized by an AUC of 0.69 and 0.82, respectively. The introduction of the second quantitative marker describing the statistical properties of scattering increased the corresponding AUC values to 0.82 and 0.91. CONCLUSIONS: Quantitative ultrasound information can characterize the tumor's pathological response better and at an earlier stage of therapy than the assessment of the reduction of its dimensions. The introduction of statistical parameters of ultrasonic backscatter to monitor the effects of chemotherapy can increase the effectiveness of monitoring and contribute to a better personalization of NAC therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Quimioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico
9.
Cancer ; 125(3): 374-381, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566762

RESUMO

BACKGROUND: Adherence to endocrine therapy for breast cancer is often inadequate, in part because of out-of-pocket costs for medication. Numerous states have enacted parity laws to limit patient cost-sharing for oral anticancer drugs. The objective of this study was to estimate the impact of these laws on patient copayments for and adherence to oral endocrine therapy for breast cancer. METHODS: Administrative health insurance claims data from 2007 to 2014 derived from a US health care database were used to identify female patients aged 18 to 64 years with invasive cancer or ductal carcinoma in situ of the breast who initiated endocrine therapy and were enrolled in fully insured health plans in states that either enacted parity legislation between 2008 and 2013 or had not yet enacted such legislation by 2015. Differences-in-differences analysis was used to compare copayments for and adherence to endocrine therapy during the 1-year period before and after each year of legislation enactment. RESULTS: In total, 6900 individuals who received 7778 unique drug therapy courses were identified. Parity legislation was associated with significant decreases in the 25th percentile of copayments for anastrozole of $4.39 (95% confidence interval [CI], -$4.52 to -$4.26; P < .001) and for exemestane of $3.08 (95% CI, -$4.80 to -$1.35; P < .001). The median copayment for exemestane decreased by $10.25 (95% CI, -$12.61 to -$7.89; P < .001). A higher median monthly copayment was significantly associated with a greater risk of medication nonadherence (adjusted risk ratio, 1.006 per dollar increase; P < .001). CONCLUSIONS: Parity laws had a modest effect on lowering the cost of anastrozole and exemestane, but more focused efforts to limit out-of-pocket costs for endocrine therapy may have a greater impact on medication adherence.


Assuntos
Antineoplásicos Hormonais , Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Custo Compartilhado de Seguro/legislação & jurisprudência , Custos de Medicamentos/legislação & jurisprudência , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Antineoplásicos Hormonais/economia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/economia , Neoplasias da Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/economia , Carcinoma Intraductal não Infiltrante/epidemiologia , Feminino , Humanos , Seguro Saúde/economia , Seguro Saúde/legislação & jurisprudência , Seguro Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Governo Estadual , Planos Governamentais de Saúde/legislação & jurisprudência , Adulto Jovem
10.
J Mammary Gland Biol Neoplasia ; 23(4): 293-301, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30206737

RESUMO

Ductal carcinoma in situ (DCIS) of the breast is a non-obligatory precursor to invasive breast carcinoma, with a variable natural history and biological potential for progression to invasive disease. Over the past 30 years, clinical trials have applied the therapeutic principles used for invasive carcinoma to treat DCIS (surgery, with or without breast radiotherapy, and post-operative endocrine therapy), with excellent survival outcomes, and in-breast recurrence rates that range from 0.5 to 1% annually. However, half of such recurrences are again in-situ lesions, and intensive therapy is likely not necessary for all patients. Current clinical research is focused on a better characterization of the potential of individual lesions to progress to invasive disease, and to identify women who would do well with lesser treatment. Three ongoing trials in the United States and Europe randomize women to active surveillance (with or without endocrine therapy) versus usual treatment with surgery and radiotherapy. The use of pre-operative endocrine therapy has been evaluated in a recently completed trial of letrozole use in postmenopausal women with DCIS; and in on-going trials of tamoxifen, used either orally, or as a 4-hydroxytamoxifen gel formulation for application to the breast skin. This review summaries the major past and current clinical trials of DCIS, and the likely trajectories of DCIS management in the near future.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Humanos
11.
Rev. argent. radiol ; 82(3): 114-123, set. 2018. ilus
Artigo em Espanhol | LILACS | ID: biblio-977272

RESUMO

Las lesiones mamarias se dividen histológicamente en dos grandes grupos, malignas y benignas. Las lesiones malignas pueden ser de origen ductal o lobulillar, siendo el carcinoma ductal infiltrante la neoplasia invasiva más frecuente. Las lesiones benignas se clasifican en no proliferativas, proliferativas sin atipias y proliferativas con atipias. Dentro de los dos últimos grupos se encuentran entidades que conllevan un alto riesgo de desarrollar carcinoma de mama, como pueden ser la hiperplasia ductal atípica, la cicatriz radial o la neoplasia lobular. Revisamos en qué consisten dichas entidades y cuáles son sus características principales en imagen, fundamentalmente en mamografía y ecografía. Si tras realizar una biopsia se obtiene uno de esos diagnósticos histológicos, es importante analizar las características imagenológicas y el tipo de procedimiento realizado (número de cilindros obtenidos, calibre de aguja...), para realizar un adecuado manejo posterior. En algunos casos la actitud a seguir será la extirpación quirúrgica completa de la lesión, mientras que en otros se podrá realizar una extirpación percutánea (mediante biopsia con aguja de vacio), o incluso seguimiento estricto por imagen. Mediante diferentes casos mostraremos nuestra experiencia y analizaremos la literatura vigente para recordar esas entidades y llegar a un consenso adecuado sobre el manejo de las mismas.


Breast lesions are divided histologically into two large groups, malignant and benign. Malignant lesions may be of ductal or lobular origin, with infiltrating ductal carcinoma being the most frequent invasive neoplasm. Benign breast lesions are classified as proliferative, proliferative without atypia and proliferative with atypia. Within the last two classifications are entities that carry a high risk of developing breast carcinoma, such as atypical ductal hyperplasia, radial scar or lobular neoplasia. We review what these entities consist of and what are their fundamental characteristics in image, fundamentally in mammography and ultrasound. When we perform one of these histological diagnoses after a biopsy, it is important to analyze the radiological characteristics and the type of procedure performed (number of cylinders, needle gauge ...) to perform an appropriate posterior management. In some cases the attitude to be followed will be the complete surgical removal of the lesion, while in others a percutaneous excision (through vacuum needle biopsy) or even strict image follow-up may be performed. Through different cases we will show our experience and analyze current literature to remember these entities and reach an adequate management consensus.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Mama/lesões , Mama/patologia , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Tumor Filoide/diagnóstico por imagem , Fasciite/diagnóstico por imagem , Carcinoma de Mama in situ/diagnóstico por imagem , Tamoxifeno/uso terapêutico , Mama/cirurgia , Mamografia , Espectroscopia de Ressonância Magnética , Ultrassonografia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Tumor Filoide/cirurgia , Cloridrato de Raloxifeno/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Fasciite/cirurgia , Carcinoma de Mama in situ/cirurgia , Carcinoma de Mama in situ/tratamento farmacológico
12.
Breast J ; 24(6): 894-901, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30033607

RESUMO

PURPOSE: Neoadjuvant systemic treatment (NST) is increasingly administered in breast cancer patients. This study was conducted to identify predictors for tumor response in the breast and axilla. METHODS: All female patients with nonmetastatic, noninflammatory breast cancer receiving NST between 2003-2013 at the Catharina Cancer Institute in Eindhoven, The Netherlands, were included. RESULTS: The majority of 216 of the 337 patients receiving NST (65%) presented with a cT2 tumor. In 159 patients (47%), the axilla was clinically node positive. A pathologic complete response (pCR) in the breast was achieved in 83 patients (24.6%), and a pCR in the axilla in 65 node-positive patients (40.9%). The triple-negative (OR 4.29, 95% CI 2.15-8.55) and hormone receptor (HR)-negative/HER2-positive tumors (OR 3.73, 95% CI 1.59-8.75) were associated with in-breast pCR. Patients with invasive lobular carcinoma (ILC) were less likely to experience in-breast pCR (OR 0.10, 95% CI 0.01-0.73) than those with invasive ductal cancer. Axillary pCR was found in 65 clinically node-positive patients (41%). Axillary pCR was more likely to occur in HR-positive/HER2-positive (OR 6.24, 95% CI 1.86-20.90) and HR-negative/HER2-positive tumors (OR 6.41, 95% CI 1.95-21.06), compared to HER2-negative disease. In-breast pCR was strongly associated with axillary pCR (OR 10.89, 95% CI 4.20-28.22). CONCLUSION: Response to NST in the breast and axilla is largely determined by receptor status, with high pCR rates occurring in HER2-positive and triple-negative tumors. For axillary pCR, in-breast pCR and HER2-positive disease are the most important predictive factors.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Adulto , Axila/patologia , Axila/cirurgia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Resultado do Tratamento
14.
Curr Oncol ; 25(2): 133-138, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29719429

RESUMO

Purpose: The mainstay of treatment for ductal carcinoma in situ (dcis) involves surgery in the form of mastectomy or lumpectomy. Inconsistency in the use of endocrine therapy (et) for dcis is evident worldwide. We sought to assess the variation in et prescribing for patients with dcis across a population-based radiotherapy (rt) program and to identify variables that predict its use. Methods: Data from a breast cancer database were obtained for women diagnosed with dcis in British Columbia from 2009 to 2014. Associations between et use and patient characteristics were assessed by chi-square test and multilevel multivariate logistic regression. The Kaplan-Meier method, with propensity score matching and Cox regression analysis, was used to assess the effects of et on overall survival (os) and relapse-free survival (rfs). Results: For the 2336 dcis patients included in the study, et use was 13% in dcis patients overall, and 17% in patients with estrogen receptor-positive (er+) tumours treated with breast-conserving surgery and rt. Significant variation in et use by treatment centre was observed (range: 8%-23%; p < 0.001), and prescription of et by individual oncologists varied in the range 0%-40%. After controlling for confounding factors, age less than 50 years [odds ratio (or): 1.72; p = 0.01], treatment centre, er+ status (or: 5.33; p < 0.001), and rt use (or: 1.77; p < 0.001) were significant predictors of et use. No difference in os or rfs with the use of et was observed. Conclusions: In this population-based analysis, 13% of patients with dcis in British Columbia received et, with variation by treatment centre (8%-23%) and individual oncologist (0%-40%). Age less than 50 years, er+ status, and rt use were most associated with et use.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Colúmbia Britânica , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/terapia , Terapia Combinada , Bases de Dados Factuais , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia Segmentar , Pessoa de Meia-Idade , Gradação de Tumores , Radioterapia Adjuvante , Receptores Estrogênicos/análise , Adulto Jovem
15.
Breast Cancer ; 25(5): 583-589, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29619758

RESUMO

BACKGROUND: Enhanced magnetic resonance imaging (MRI) and ultrasonography (US) are used to assess residual lesions after preoperative chemotherapy before surgery. However, residual lesion assessments based on preoperative imaging often differ from postoperative pathologic diagnoses. We retrospectively reviewed the accuracy of preoperative residual lesion assessments, including ductal carcinoma in situ (DCIS) cases to find criteria for cases in which surgery can be omitted. METHODS: We reviewed 201 patients who received preoperative chemotherapy and surgery in our hospital from January 2013 to November 2016. Presurgical evaluations regarding the possible existence of residual lesions, and clinical Complete Response (cCR) or non-cCR, were compared with postoperative pathological diagnoses. RESULTS: Of the 201 patients, 52 were diagnosed with cCR, and 39 with pathological complete response (pCR). Predictions for residual lesions were 86.4% sensitive, 76.9% specific, and 84.6% accurate. When patients were divided into 4 groups by estrogen receptor (ER) and HER2 status, sensitivity in each group was ER+/HER2-: 91.4%; ER-/HER2-: 94.1%; ER+/HER2+: 78.6%; and ER-/HER2+: 78.5%. Of the 22 patients preoperatively assessed with cCR, but diagnosed with non-pCR, the median invasive residual tumor size was 2 mm (range 0-46 mm); 5 patients (22.7%) had only DCIS. CONCLUSIONS: Predicting residual lesions after preoperative chemotherapy by using MRI and US is a reasonable strategy. However, current methods are inadequate for identifying patients who can omit surgery; therefore, a new strategy for detecting small tumors in these patients is needed.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Imagem por Ressonância Magnética/métodos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasia Residual , Cuidados Pré-Operatórios , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Estudos Retrospectivos , Resultado do Tratamento
16.
Eur J Pharm Sci ; 121: 118-125, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-29698706

RESUMO

Although systemic administration of chemotherapeutic agents is routinely used for treating invasive breast cancer, the only therapeutic options for ductal carcinoma in situ (DCIS) are surgery and radiation. Treating DCIS by delivering drugs locally to the affected milk duct offers significant advantages over systemic administration, including reduced systemic and breast toxicities, as well as a greatly reduced need for surgery and radiation. In this study, mammary gland retention and toxicity of intraductally administered poly(ethylene) glycol-doxorubicin (PEG-DOX) polymeric conjugate nanocarriers of varying molecular sizes and architectures were investigated. Nanocarriers were formed by conjugating one or more copies of doxorubicin to PEG polymers, of varying molecular weights (5, 10, 20, and 40 kDa) and architectures (linear, four-arm and eight-arm). Cytotoxicity against MCF7 cells, a human breast cancer cell line, was assessed, and IC50 values were calculated. The nanocarriers were intraductally administered into the mammary glands of female retired breeder Sprague-Dawley rats. Whole body images were captured using in vivo optical imaging, and changes in ductal structure as well local inflammation were monitored. Fluorescence intensities were monitored, over time, to evaluate nanocarrier mammary gland retention half-lives (t1/2). The IC50 values of PEG-DOX nanocarriers against MCF7 cells were 40 kDa PEG-(DOX)4 (1.23 µM) < 5 kDa PEG-DOX (1.76 µM) < 40 kDa PEG-(DOX)8 (3.49 µM) < 10 kDa PEG-DOX (3.86 µM) < 20 kDa PEG-DOX (8.96 µM) < 40 kDa PEG-DOX (18.11 µM), whereas the IC50 of free DOX was only 0.14 µM. The t1/2 of linear 5, 20, and 40 kDa nanocarriers were 2.2 ±â€¯0.3, 3.6 ±â€¯0.6, and 13.1 ±â€¯3.4 h, whereas the retention t1/2 of 4- and 8-arm 40 kDa nanocarriers were 14.9 ±â€¯5.6 h and 11.9 ±â€¯2.9 h, respectively. The retention t1/2 of free doxorubicin was 2.0 ±â€¯0.4 h, which was significantly shorter than that of the linear and branched 40 kDa PEG-DOX nanocarriers. Increased molecular weight and decreased branching both demonstrated a strong correlation to enhanced mammary gland retention. Intraductally administered free doxorubicin resulted in ductal damage, severe inflammation and generation of atypical cell neoplasms, whereas PEG-DOX nanocarriers induced only minor and transient inflammation (i.e., damaged epithelial cells and detached cellular debris). The 40 kDa 4-arm PEG-DOX nanocarrier demonstrated the longest ductal retention half-life, the lowest IC50 (i.e., most potent), and minimal ductal damage and inflammation. The current results suggest that PEG-DOX nanocarriers with prolonged ductal retention may present the best option for intraductal treatment of DCIS, due to their low local toxicity and potential for sustained therapeutic effect.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Glândulas Mamárias Animais/metabolismo , Nanoestruturas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Animais , Antineoplásicos/química , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/metabolismo , Doxorrubicina/química , Vias de Administração de Medicamentos , Portadores de Fármacos/química , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/metabolismo , Nanoestruturas/química , Polietilenoglicóis/química , Ratos Sprague-Dawley
17.
Drug Deliv ; 25(1): 654-667, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29495885

RESUMO

Considering that breast cancer usually begins in the lining of the ducts, local drug administration into the ducts could target cancers and pre-tumor lesions locally while reducing systemic adverse effects. In this study, a cationic bioadhesive nanoemulsion was developed for intraductal administration of C6 ceramide, a sphingolipid that mediates apoptotic and non-apoptotic cell death. Bioadhesive properties were obtained by surface modification with chitosan. The optimized nanoemulsion displayed size of 46.3 nm and positive charge, properties that were not affected by ceramide encapsulation (0.4%, w/w). C6 ceramide concentration necessary to reduce MCF-7 cells viability to 50% (EC50) decreased by 4.5-fold with its nanoencapsulation compared to its solution; a further decrease (2.6-fold) was observed when tributyrin (a pro-drug of butyric acid) was part of the oil phase of the nanocarrier, a phenomenon attributed to synergism. The unloaded nanocarrier was considered safe, as indicated by a score <0.1 in HET-CAM models, by the high survival rates of Galleria mellonella larvae exposed to concentrations ≤500 mg/mL, and absence of histological changes when intraductally administered in rats. Intraductal administration of the nanoemulsion prolonged drug localization for more than 120 h in the mammary tissue compared to its solution. These results support the advantage of the optimized nanoemulsion to enable mammary tissue localization of C6 ceramide.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Galinhas , Emulsões , Feminino , Humanos , Células MCF-7 , Nanopartículas/metabolismo , Ratos , Resultado do Tratamento
18.
Breast J ; 24(4): 555-560, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29498448

RESUMO

NCCN guidelines recommend tamoxifen (TAM) for adjuvant treatment of ductal carcinoma in situ (DCIS). TAM has side effects that can potentially complicate treatment recommendations and patient acceptance. It is unknown how well-accepted this recommended therapy is for the adolescent and young adult (AYA) patient population with DCIS. The NCDB was used to identify patients aged 15-39 with DCIS treated between 2000 and 2012. Patient demographic, socioeconomic, and treatment data were collected. Chi-squared test and multivariate analysis were used for statistical assessment. A total of 3988 women were identified of which 1795 (45%) were recommended for endocrine therapy. Age > 30 (OR 1.31, 95%CI 1.01-1.70), Black (OR 1.40, 95% CI 1.12-1.65), or Asian (OR 1.45, 95% CI 1.08-1.94) race, treatment at a nonacademic facility (OR 0.71, 95% CI 0.56-0.91), geographic location of treating facility, receipt of radiation (OR 5.30, 95% CI 4.59-6.11), and negative margins (OR 2.14, 95% CI 1.47-3.11) were significant predictors of recommendation for endocrine therapy. Of those recommended, 1484 (83%) accepted treatment. Age, race, and annual income were significant variables affecting acceptance. Overall, only 37.2% (1484 of 3988) of women in this study initiated endocrine therapy for treatment of DCIS. Our results demonstrate that little over a third of patients in the AYA cohort receive endocrine therapy as treatment for DCIS. The bias appears to lie in physician recommendation because when recommended, the majority of patients accept treatment. Factors exist both medical and nonmedical that appear to influence these treatment decisions.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Tamoxifeno/administração & dosagem , Adolescente , Adulto , Fatores Etários , Antineoplásicos Hormonais/efeitos adversos , Atitude do Pessoal de Saúde , Quimioterapia Adjuvante/métodos , Distribuição de Qui-Quadrado , Feminino , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Sistema de Registros , Tamoxifeno/efeitos adversos , Estados Unidos , Adulto Jovem
19.
Breast Cancer Res Treat ; 169(2): 311-322, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29383628

RESUMO

PURPOSE: To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. METHODS: Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. CONCLUSION: Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Sistema de Registros , Análise de Sobrevida
20.
Cancer Prev Res (Phila) ; 11(4): 203-214, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29453232

RESUMO

Obesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I-III breast cancer, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of TNFα. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL1ß, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 to November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA (P < 0.001) but not placebo. Treatment with DHA did not alter levels of TNFα (P = 0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared with placebo. Cancer Prev Res; 11(4); 203-14. ©2018 AACRSee related editorial by Fabian and Kimler, p. 187.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Doença da Mama Fibrocística/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , Método Duplo-Cego , Feminino , Doença da Mama Fibrocística/genética , Doença da Mama Fibrocística/patologia , Seguimentos , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Prognóstico
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