Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 852
Filtrar
1.
Zhonghua Wai Ke Za Zhi ; 59(3): 222-227, 2021 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-33685057

RESUMO

Objective: To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer. Methods: Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison. Results: Patients who received trastuzumab-based therapy(n=294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab(n=177) (84.4% vs. 72.4%, χ²=4.095, P=0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P>0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ²=5.340, P=0.021), but they had similar OS (91.4% vs. 89.1%, χ²=1.008, P=0.315). Conclusions: TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Humanos , Estudos Retrospectivos , Trastuzumab/administração & dosagem
2.
Medicine (Baltimore) ; 100(10): e24995, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725875

RESUMO

BACKGROUND: Adjuvant trastuzumab improves survival outcomes of human epidermal receptor 2 positive early breast cancer patients. Currently, administration of 12 months adjuvant trastuzumab is the standard therapy. However, whether 6 months treatment is non-inferior to the standard 12 months treatment remains controversial. METHODS: Relevant records were searched in PubMed, Cochrane Library, Web of Science, and EMBASE through Jan 14, 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were meta-analyzed. The primary endpoint was DFS with a non-inferiority hazard margin of 1.2 and the second was OS with 1.43. RESULTS: Three randomized clinical studies met the inclusion criteria, including 3974 patients in 6 months group and 3976 in 12 months group. HR for DFS was 1.18 (95% CI 0.97-1.44, P = .09), with the non-inferiority margin comprised in the 95% CI. HR for OS was 1.14 (95% CI 0.98-1.32, P= .08), whereas the upper limit of 95% CI did not exceed the non-inferiority hazard margin. CONCLUSION: Our analysis failed to show that 6 months treatment was non-inferior to 12 months treatment in improving the DFS. Although the non-inferiority of the 6-month adjuvant trastuzumab treatment was found for OS, considering that breast cancer patients should receive additional systematic therapies when disease progression or relapse happens, we suggest that 12 months adjuvant trastuzumab treatment should remain the standard therapeutic strategy for patients with early human epidermal receptor 2 positive breast cancer.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/epidemiologia , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Mama/imunologia , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante/métodos , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Mastectomia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Fatores de Tempo
4.
Cancer Sci ; 112(3): 1326-1330, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33543819

RESUMO

Near-infrared photoimmunotherapy (NIR-PIT) is a new type of cancer treatment, which was recently approved in Japan for patients with inoperable head and neck cancer. NIR-PIT utilizes antibody-IRDye700DX (IR700) conjugates and NIR light at a wavelength of 690 nm. NIR light exposure leads to physicochemical changes in the antibody-IR700 conjugate cell receptor complex, inducing rapid necrotic cell death. Just as fluorescence guided surgery is useful for surgeons to resect tumors completely, real-time information of tumor locations would help clinicians irradiate NIR light more precisely. IR700 is a fluorescence dye that emits at 702 nm; however, there is no clinically available device optimized for detecting this fluorescence. On the other hand, many indocyanine green (ICG) fluorescence imaging devices have been approved for clinical use. Therefore, we investigated whether LIGHTVISION, one of the clinically available ICG cameras, could be employed for tumor detection. We hypothesized that irradiation with even low-power 690-nm laser light, attenuated by 99% with a neutral-density filter, could be detected with LIGHTVISION without fluorescence decay or therapeutic effect because of the long emission tail of IR700 beyond 800 nm (within the detection range of LIGHTVISION). We demonstrated that the LIGHTVISION camera, originally designed for ICG detection, can detect the tail of IR700 fluorescence in real time, thus enabling the visualization of target tumors.


Assuntos
Imunoterapia/métodos , Neoplasias/diagnóstico por imagem , Imagem Óptica/instrumentação , Fototerapia/métodos , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Feminino , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/química , Indóis/administração & dosagem , Indóis/química , Camundongos , Neoplasias/terapia , Compostos de Organossilício/administração & dosagem , Compostos de Organossilício/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Trastuzumab/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Anticancer Res ; 41(1): 485-496, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419847

RESUMO

BACKGROUND/AIM: Subcutaneous Herceptin (HER SC) has been shown to be equally effective and safe compared to intravenous Herceptin (HER i.v.) application in early HER2-positive breast cancer (HER2+ BC). However, real-world data from the subcutaneous application are currently limited. PATIENTS AND METHODS: Based on a non-interventional study (NIS), data from routine clinical use of HER SC have been gathered between 2013 and 2018 in 135 hospitals and open-care practices throughout Germany. RESULTS: A total of 265 patients were recruited in the neo-adjuvant and 605 patients in the adjuvant setting. Primary effectiveness endpoint in the neoadjuvant treatment setting was pathological complete response rate, which was achieved in 41.5%. Primary endpoint in the adjuvant setting was disease free survival rate after 2 years (94.9%). Safety results from the study were comparable to the well-known safety profile of HER i.v. including preferred terms, incidence, severity, including cardiac events. No new safety signals were detected. CONCLUSION: Effectiveness and safety of HER SC were comparable to data from HER i.v. in early HER2+ BC.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Duração da Terapia , Feminino , Alemanha , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Qualidade de Vida , Retratamento , Trastuzumab/efeitos adversos , Resultado do Tratamento , Adulto Jovem
7.
ESMO Open ; 6(1): 100007, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33450658

RESUMO

Treatment of patients with cancer in hospitals or clinics is resource-intensive and imposes a burden on patients. 'Flexible care' is a term that can be used to describe treatment administered outside the oncology ward, oncological outpatient clinic or office-based oncologist setting. Programmes that reduce travel burden by bringing cancer treatment to the patient's home, workplace or closer to the patient's home, in the form of satellite clinics or mobile cancer units, expand treatment capacity and are well received. Clinical trial data show that, compared with intravenous administration, subcutaneous (s.c.) administration of trastuzumab is preferred by patients with breast cancer (BC), saves healthcare professionals' (HCPs) time, reduces drug preparation and administration time and reduces direct and indirect costs. As such, s.c. trastuzumab is well suited to flexible care. The results of a Belgian study (BELIS) show that home administration of s.c. trastuzumab is feasible and preferred by patients with BC. Numerous programmes and pilot studies in Europe show that s.c. trastuzumab can be administered effectively in the patient's home, in primary care settings or local hospitals. Such programmes require planning, training, careful patient selection and technology to link patients, caregivers and specialists in oncology clinics. Once these elements are in place, flexible care offers patients with BC a choice of how treatment may be delivered and lead to improved quality of life, while reducing pressure on HCPs and hospitals. The concept of flexible care is particularly relevant amid the COVID-19 pandemic where guidelines have been developed encouraging remote care.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Serviços Hospitalares de Assistência Domiciliar , Trastuzumab/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , /virologia , Feminino , Humanos , Injeções Subcutâneas , Oncologia/economia , Oncologia/métodos , Oncologia/tendências , Pandemias , Qualidade de Vida , /fisiologia
8.
Lancet Oncol ; 22(1): 85-97, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33357420

RESUMO

BACKGROUND: A subcutaneous formulation of pertuzumab and trastuzumab with recombinant human hyaluronidase in one ready-to-use, fixed-dose combination vial (pertuzumab, trastuzumab, and hyaluronidase-zzxf) was approved by the US Food and Drug Administration (FDA) on June 29, 2020. We report the primary analysis of the FeDeriCa study, which was designed to assess the pharmacokinetics, efficacy, and safety of the fixed-dose subcutaneous formulation compared to intravenous pertuzumab plus trastuzumab in patients with HER2-positive early breast cancer in the neoadjuvant-adjuvant setting. METHODS: FeDeriCa, a randomised, open-label, international, multicentre, non-inferiority, phase 3 study, was done across 106 sites in 19 countries. Patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1, HER2-positive, operable, locally advanced, or inflammatory stage II-IIIC breast cancer, and a left ventricular ejection fraction of 55% or more were randomly assigned (1:1), using a voice-based or web-based response system, to receive intravenous pertuzumab (840 mg loading dose, followed by 420 mg maintenance doses) plus intravenous trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg maintenance doses) or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (1200 mg pertuzumab plus 600 mg trastuzumab loading dose in 15 mL, followed by 600 mg pertuzumab plus 600 mg trastuzumab maintenance doses in 10 mL), both administered every 3 weeks with neoadjuvant chemotherapy. Patients were stratified by hormone receptor status, clinical stage, and chemotherapy regimen. The investigator selected one of the two protocol-approved standard chemotherapy regimens before randomisation. Four cycles of HER2-targeted therapy were administered concurrently with the taxane. After surgery, patients continued the HER2-targeted therapy to receive an additional 14 cycles (total of 18). The primary endpoint was non-inferiority of the cycle 7 pertuzumab serum trough concentration (Ctrough; ie, cycle 8 predose pertuzumab concentration) within the fixed-dose combination for subcutaneous injection versus intravenous pertuzumab plus trastuzumab in the per-protocol pharmacokinetic population (all enrolled patients who adhered to prespecified criteria for pharmacokinetic assessment). Non-inferiority was concluded if the lower bound of the 90% CI of the geometric mean ratio was 0·8 or higher. The safety population included all patients who received at least one dose of study medication, including chemotherapy or HER2-targeted therapy. Enrolment, neoadjuvant therapy, and surgery have been completed; adjuvant treatment and follow-up are ongoing. The trial is registered with ClinicalTrials.gov, NCT03493854. FINDINGS: Between June 14, 2018, and Dec 24, 2018, 252 patients were randomly assigned to the intravenous infusion group and 248 to the fixed-dose combination group. The geometric mean ratio of pertuzumab serum Ctrough subcutaneous to serum Ctrough intravenous was 1·22 (90% CI 1·14-1·31). The most common grade 3-4 adverse events occurring during neoadjuvant treatment with HER2-targeted therapy plus chemotherapy in 5% or more of patients were neutropenia (34 [13%] of 252 patients in the intravenous infusion group vs 35 [14%] of 248 patients in the fixed-dose combination group), decreased neutrophil count (31 [12%] vs 27 [11%]), febrile neutropenia (14 [6%] vs 16 [6%]), diarrhoea (12 [5%] vs 17 [7%]), and decreased white blood cell count (18 [7%] vs nine [4%]). At least one treatment-related serious adverse event was reported in 25 (10%) patients in the intravenous infusion group and 26 (10%) patients in the fixed-dose combination group. One patient in each treatment group had an adverse event that led to death (urosepsis in the intravenous infusion group and acute myocardial infarction in the fixed-dose combination group); neither death was related to HER2-targeted therapy. INTERPRETATION: The study met its primary endpoint: the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection provides non-inferior cycle 7 pertuzumab serum Ctrough concentrations to intravenous pertuzumab plus trastuzumab in the neoadjuvant setting with comparable total pathological complete response rates, supporting the FDA approval. Safety was similar between treatment groups, and in line with other pertuzumab, trastuzumab, and chemotherapy trials. Follow-up is ongoing for long-term outcomes, including efficacy and long-term safety. FUNDING: F Hoffmann-La Roche and Genentech.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Trastuzumab/administração & dosagem , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Hialuronoglucosaminidase/administração & dosagem , Injeções Subcutâneas , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Fatores de Tempo , Trastuzumab/efeitos adversos , Trastuzumab/farmacocinética , Resultado do Tratamento
9.
Lancet Oncol ; 21(11): 1455-1464, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152285

RESUMO

BACKGROUND: In early-stage HER2-positive breast cancer, escalation or de-escalation of systemic therapy is a controversial topic. As an aid to treatment decisions, we aimed to develop a prognostic assay that integrates multiple data types for predicting survival outcome in patients with newly diagnosed HER2-positive breast cancer. METHODS: We derived a combined prognostic model using retrospective clinical-pathological data on stromal tumour-infiltrating lymphocytes, PAM50 subtypes, and expression of 55 genes obtained from patients who participated in the Short-HER phase 3 trial. The trial enrolled patients with newly diagnosed, node-positive, HER2-positive breast cancer or, if node negative, with at least one risk factor (ie, tumour size >2 cm, histological grade 3, lymphovascular invasion, Ki67 >20%, age ≤35 years, or hormone receptor negativity), and randomly assigned them to adjuvant anthracycline plus taxane-based combinations with either 9 weeks or 1 year of trastuzumab. Trastuzumab was administered intravenously every 3 weeks (8 mg/kg loading dose at first cycle, and 6 mg/kg thereafter) for 18 doses or weekly (4 mg/kg loading dose in the first week, and 2 mg/kg thereafter) for 9 weeks, starting concomitantly with the first taxane dose. Median follow-up was 91·4 months (IQR 75·1-105·6). The primary objective of our study was to derive and evaluate a combined prognostic score associated with distant metastasis-free survival (the time between randomisation and distant recurrence or death before recurrence), an exploratory endpoint in Short-HER. Patient samples in the training dataset were split into a training set (n=290) and a testing set (n=145), balancing for event and treatment group. The training set was further stratified into 100 iterations of Monte-Carlo cross validation (MCCV). Cox proportional hazard models were fit to MCCV training samples using Elastic-Net. A maximum of 92 features were assessed. The final prognostic model was evaluated in an independent combined dataset of 267 patients with early-stage HER2-positive breast cancer treated with different neoadjuvant and adjuvant anti-HER2-based combinations and from four other studies (PAMELA, CHER-LOB, Hospital Clinic, and Padova) with disease-free survival outcome data. FINDINGS: From Short-HER, data from 435 (35%) of 1254 patients for tumour size (T1 vs rest), nodal status (N0 vs rest), number of tumour-infiltrating lymphocytes (continuous variable), subtype (HER2-enriched and basal-like vs rest), and 13 genes composed the final model (named HER2DX). HER2DX was significantly associated with distant metastasis-free survival as a continuous variable (p<0·0001). HER2DX median score for quartiles 1-2 was identified as the cutoff to identify low-risk patients; and the score that distinguished quartile 3 from quartile 4 was the cutoff to distinguish medium-risk and high-risk populations. The 5-year distant metastasis-free survival of the low-risk, medium-risk, and high-risk populations were 98·1% (95% CI 96·3-99·9), 88·9% (83·2-95·0), and 73·9% (66·0-82·7), respectively (low-risk vs high-risk hazard ratio [HR] 0·04, 95% CI 0·0-0·1, p<0·0001). In the evaluation cohort, HER2DX was significantly associated with disease-free survival as a continuous variable (HR 2·77, 95% CI 1·4-5·6, p=0·0040) and as group categories (low-risk vs high-risk HR 0·27, 0·1-0·7, p=0·005). 5-year disease-free survival in the HER2DX low-risk group was 93·5% (89·0-98·3%) and in the high-risk group was 81·1% (71·5-92·1). INTERPRETATION: The HER2DX combined prognostic score identifies patients with early-stage, HER2-positive breast cancer who might be candidates for escalated or de-escalated systemic treatment. Future clinical validation of HER2DX seems warranted to establish its use in different scenarios, especially in the neoadjuvant setting. FUNDING: Instituto Salud Carlos III, Save the Mama, Pas a Pas, Fundación Científica, Asociación Española Contra el Cáncer, Fundación SEOM, National Institutes of Health, Agenzia Italiana del Farmaco, International Agency for Research on Cancer, and the Veneto Institute of Oncology, and Italian Association for Cancer Research.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Prognóstico , Receptor ErbB-2/genética , Trastuzumab/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab/efeitos adversos , Resultado do Tratamento
10.
Medicine (Baltimore) ; 99(44): e22886, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126339

RESUMO

BACKGROUND: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that retains the antitumor effects of trastuzumab while also delivering the cytotoxic antimicrotubule agent, DM1, directly to tumor cells that overexpress human epidermal growth factor receptor 2. The pharmacokinetic (PK) profile of T-DM1 has been well characterized in Western, Asian, and Japanese patients; this single-center, phase I study (NCT03153163) examined the PK of T-DM1 and safety specifically in Chinese patients. METHODS: Patients with locally advanced or metastatic breast cancer, previously treated with trastuzumab and a taxane, received open-label T-DM1 at 3.6 mg/kg every 3 weeks. Serum T-DM1 and total trastuzumab, and plasma DM1 were evaluated, and PK parameters were calculated using standard noncompartmental approaches. Adverse events (AEs) were assessed, and immunogenicity was evaluated by measuring antidrug antibodies to T-DM1. RESULTS: Among 11 Chinese patients, mean (±standard deviation) PK parameters (maximum serum concentration, 77.6 ±â€Š17.4 µg/mL; clearance 11.0 ±â€Š2.6 mL/d/kg; terminal half-life 3.8 ±â€Š1.0 days) were similar to those previously reported in Western and Japanese patients. One patient transiently developed antidrug antibodies, which did not appear to influence safety or PK. T-DM1 was generally well tolerated. Grade 3-4 AEs occurred in 7 patients (63.6%) and serious AEs occurred in 4 patients (36.4%). Platelet count decrease was the most common all-grade AE (10/11; 90.9%), grade 3-4 AE (5/11; 45.5%), and serious AE (3/11; 27.3%), but did not appear to be associated with any clinically significant bleeding events. CONCLUSIONS: T-DM1 PK in Chinese patients was consistent with those in global and Asian populations, supporting its use in patients with advanced human epidermal growth factor receptor 2-positive breast cancer following progression on trastuzumab and a taxane. The safety profile of T-DM1 was consistent with prior experience.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Trastuzumab , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , China , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/farmacocinética , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(44): e22929, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126355

RESUMO

RATIONALE: The incidence of pregnancy-associated breast cancer (PABC) is increasing nowadays, and its diagnosis and treatment remain complicated due to the consideration of the fetus. The available data on PABC are primarily derived from case reports since there are ethical restrictions on conducting randomized clinical trials. In the present work, we reported a case of the human epidermal growth factor receptor 2 (HER2)-positive PABC and described the diagnosis and treatment for such type of breast cancer. PATIENT CONCERNS: A 27-year-old patient was admitted to our hospital with the complaints of right breast mass for 3 days, and she was a first-time pregnant woman with a single live intrauterine fetus at 26 + 3 weeks of gestation. Physical examination of the right breast revealed a palpable and hard mass with obscure boundaries (5.0 cm × 4.0 cm) in the upper outer quadrant. Significant axillary lymph nodes (2.0 cm) were also present. DIAGNOSIS: PABC. INTERVENTION: To protect the fetus, breast ultrasonography was used to test her breast mass, a core needle biopsy was adopted to confirm the diagnosis, and abdominal ultrasound and chest X-ray were used to evaluate the metastasis. The patient was scheduled for neoadjuvant therapy using bi-weekly pirarubicin in combination with cyclophosphamide (AC) without anti-HER2 therapy for consideration of the fetus's safety. After 4 cycles of AC, the patient delivered a healthy male infant. After the delivery, all the treatments were carried out according to the standard recommendation for HER2 + breast cancer as non-pregnant patients. OUTCOMES: After the surgery, the disease-free survival for the patient was 12 months until brain metastasis was diagnosed. She was still undergoing second-line anti-HER2 therapy and currently in a stable situation. Besides, the child was also healthy so far. LESSONS: The methods for the diagnosis and treatment of PABC that result in teratogenesis should be avoided to protect the fetus. Mammogram and chest X-ray were safe approaches for the fetus. Moreover, chemotherapy-based on pirarubicin in combination with cyclophosphamide had no risk to the fetus.


Assuntos
Neoplasias da Mama , Ciclofosfamida/administração & dosagem , Doxorrubicina/análogos & derivados , Mastectomia Radical Extensa/métodos , Cuidado Pós-Natal/métodos , Complicações Neoplásicas na Gravidez , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Adulto , Antineoplásicos/administração & dosagem , Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Doxorrubicina/administração & dosagem , Feminino , Idade Gestacional , Humanos , Estadiamento de Neoplasias , Gravidez , Complicações Neoplásicas na Gravidez/metabolismo , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Resultado da Gravidez , Ultrassonografia Mamária/métodos
12.
Isr Med Assoc J ; 9(22): 498-502, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954696

RESUMO

BACKGROUND: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment. OBJECTIVES: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD. RESULTS: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e' septal (P < 0.001). CONCLUSIONS: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Cardiotoxicidade/etiologia , Feminino , Humanos , Israel , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente
13.
Int J Nanomedicine ; 15: 5433-5443, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801698

RESUMO

Background: Human epidermal growth factor receptor2 (Her2) positive breast cancer represents 25% of breast cancer cases. Targeted therapy with Her2 monoclonal antibody, trastuzumab (TZ), represents the first-line treatment for this type of breast cancer. In addition, neratinib, an irreversible inhibitor of the HER-2 receptor tyrosine kinase, has recently been approved as adjuvant therapy to TZ. This study aims to formulate (TZ)-grafted dendrimers loaded with neratinib, allowing a dual treatment alongside reducing the associated resistance as well as targeted therapy. Methods: TZ was conjugated on the surface of dendrimer using hetero-cross linker, MAL-PEG-NHS, and the zeta potential, and in vitro release of neratinib from dendrimers was characterized. Formulated dendrimers were also fluorescently conjugated with fluorescein isothiocyanate to visualize and quantify their SKBR-3 cellular uptake. Results: The G4 PAMAM dendrimer showed successful encapsulation of neratinib and a sustained release profile. Comparative in vitro studies revealed that these TZ-targeted dendrimers loaded with neratinib were more selective and have higher antiproliferation activity against SKBR-3 cells compared to neratinib alone and neratinib loaded dendrimer. Conclusion: In the current study, neratinib loaded in plain and trastuzumab-grafted dendrimer were successfully prepared. Enhanced cellular uptake of trastuzumab conjugated dendrimers was shown, together with a higher cytotoxic effect than plain neratinib dendrimers. These findings suggest the potential of TZ-conjugated dendrimers as targeting carrier for cytotoxic drugs, including neratinib.


Assuntos
Dendrímeros/química , Nanocápsulas/administração & dosagem , Nylons/química , Quinolinas/química , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Dendrímeros/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Fluoresceína-5-Isotiocianato , Humanos , Terapia de Alvo Molecular/métodos , Nanocápsulas/química , Poliaminas/química , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Trastuzumab/química , Trastuzumab/farmacocinética
14.
Cancer Treat Rev ; 88: 102046, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32599393

RESUMO

Leptomeningeal Metastases (LM) is a turning point in terms of prognosis and quality of life of patients with breast cancer (BC). Intrathecal therapy is largely used for the treatment of breast cancer LM. In this metanalysis with meta-regression, we gathered data on intrathecal (IT) trastuzumab administration in patients with HER2 positive breast cancer with LM. A total of 24 articles (58 patients) were included in the study and intrathecal trastuzumab was used in all patients. The mean age at IT administration was 50.7 years (SD 11.4, range 24-80) and the mean total dose of IT trastuzumab was 711.9 mg (SD 634.9, median 450). IT trastuzumab was used both alone (n = 20) and in combination with systemic pharmacotherapy (n = 37). No serious adverse events were reported in 87.9% of cases. In this selected population a significant clinical improvement was observed in 55.0% of cases while stabilization was reported in 14% of cases. CSF response was observed in 55.6% of the cases. MRI was improved or stable in 70.8% of the cases. Interestingly, the CNS-PFS was 5.2 months and the median OS was 13.2 months. A clinical improvement (HR 0.13, 95% CI 0.03-0.49) and CSF response (HR 0.13, 95% CI 0.03-0.58) were associated with a longer CNS-PFS. The association of longer CNS-PFS with radio- or neurosurgery prior to the administration of IT trastuzumab did not reach statistical significance. This metanalysis with meta-regression indicates that IT trastuzumab in patients with HER2 positive breast cancer LM might be a safe and effective treatment, but further prospective studies are needed to definitively prove such a point.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Lapatinib/administração & dosagem , Carcinomatose Meníngea/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Ensaios Clínicos Fase I como Assunto , Feminino , Humanos , Injeções Espinhais , Lapatinib/efeitos adversos , Carcinomatose Meníngea/enzimologia , Carcinomatose Meníngea/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Trastuzumab/efeitos adversos
15.
Lancet Oncol ; 21(6): 763-775, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32353342

RESUMO

BACKGROUND: Patients with HER2-positive breast cancer who have received two or more previous therapies for advanced disease have few effective treatment options. The monarcHER trial aimed to compare the efficacy of abemaciclib plus trastuzumab with or without fulvestrant with standard-of-care chemotherapy of physician's choice plus trastuzumab in women with advanced breast cancer. METHODS: This phase 2, three-group, open-label trial was done across 75 hospitals, clinics, and medical centres in 14 countries. Eligible patients were women aged 18 years or older, who had hormone receptor-positive, HER2-positive advanced breast cancer with unresectable, locally advanced, recurrent or metastatic disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and who had previously received at least two HER2-targeted therapies for advanced disease. Patients were randomly assigned 1:1:1 to the abemaciclib, trastuzumab, and fulvestrant (group A), abemaciclib and trastuzumab (group B), or standard-of-care chemotherapy and trastuzumab (group C). Oral abemaciclib 150 mg 12 hourly was administered on days 1-21 of a 21-day cycle, intravenous trastuzumab 8 mg/kg on cycle 1 day 1, followed by 6 mg/kg on day 1 of each subsequent 21-day cycle, and intramuscular fulvestrant 500 mg on days 1, 15, and 29 and once every 4 weeks thereafter. Standard-of-care chemotherapy was administered as specified by the product label. Randomisation was by a computer-generated random sequence by means of an interactive web-response system and stratified by number of previous systemic therapies for advanced breast cancer and measurable versus non-measurable disease. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, first testing group A versus group C and, if this result was significant, then group B versus group C. Safety was assessed in all patients who had received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT02675231) and is ongoing for long-term survival follow-up. FINDINGS: Between May 31, 2016, and Feb 28, 2018, 325 patients were screened, of whom 237 eligible patients were enrolled and randomly assigned to groups A (n=79), B (n=79), and C (n=79). Median follow-up was 19·0 months (IQR 14·7-25·1). The study met its primary endpoint, showing a significant difference at the prespecified two-sided α of 0·2 in median progression-free survival between group A (8·3 months, 95% CI 5·9-12·6) and group C (5·7 months, 5·4-7·0; HR 0·67 [95% CI 0·45-1·00]; p=0·051). No difference was observed between median progression-free survival in group B (5·7 months, 95% CI 4·2-7·2) and group C (HR 0·94 [0·64-1·38]; p=0·77). The most common grade 3-4 treatment-emergent adverse event in groups A, B, and C was neutropenia (21 [27%] of 78 patients, 17 [22%] of 77, and 19 [26%] of 72). The most common serious adverse events were: in group A, pyrexia (three [4%]), diarrhoea (two [3%]), urinary tract infection (two [3%]), and acute kidney injury (two [3%]); in group B, diarrhoea (two [3%]) and pneumonitis (two [3%]); and in group C, neutropenia (four [6%]) and pleural effusion (two [3%]). Two deaths were attributed to treatment: one due to pulmonary fibrosis in group B and one due to febrile neutropenia in group C. INTERPRETATION: The combination of abemaciclib, fulvestrant, and trastuzumab significantly improved progression-free survival versus standard-of-care chemotherapy plus trastuzumab while showing a tolerable safety profile. Our results suggest that a chemotherapy-free regimen might potentially be an alternative treatment option for patients with hormone receptor-positive, HER2-positive advanced breast cancer. FUNDING: Eli Lilly and Company.


Assuntos
Aminopiridinas/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Antagonistas do Receptor de Estrogênio/administração & dosagem , Fulvestranto/administração & dosagem , Receptor ErbB-2/antagonistas & inibidores , Receptores Estrogênicos/efeitos dos fármacos , Trastuzumab/administração & dosagem , Idoso , Aminopiridinas/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Argentina , Austrália , Benzimidazóis/efeitos adversos , Brasil , Neoplasias da Mama/enzimologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Progressão da Doença , Antagonistas do Receptor de Estrogênio/efeitos adversos , Europa (Continente) , Feminino , Fulvestranto/efeitos adversos , Humanos , Pessoa de Meia-Idade , América do Norte , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , República da Coreia , Transdução de Sinais , Fatores de Tempo , Trastuzumab/efeitos adversos
17.
Lancet Oncol ; 21(6): 821-831, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32437664

RESUMO

BACKGROUND: Addition of trastuzumab to first-line chemotherapy improves overall survival in patients with HER2-positive metastatic gastric cancer. We assessed the safety and activity of pembrolizumab in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric (gastric, oesophageal, or gastroesophageal junction) cancer. METHODS: This study was an investigator-initiated, open-label, non-randomised, single-arm, single centre, phase 2 trial in patients aged 18 years or older with HER2-positive metastatic oesophagogastric cancer. Eligible patients had measurable or evaluable non-measurable disease, Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and left ventricular ejection fraction of at least 53%. Patients were eligible to receive an initial induction cycle of 200 mg flat dose of intravenous pembrolizumab and 8 mg/kg loading dose of intravenous trastuzumab. For subsequent cycles, patients received 130 mg/m2 of intravenous oxaliplatin or 80 mg/m2 of cisplatin on day 1, 850 mg/m2 of oral capecitabine twice a day for 2 weeks followed by 1 week off (or intravenous 5-fluorouracil, 800 mg/m2 per day on days 1-5), and a 200 mg flat dose of intravenous pembrolizumab, and 6 mg/kg of trastuzumab, administered on day 1 of each 3-week cycle. The primary endpoint was 6-month progression-free survival, defined as the proportion of patients alive and free of progression at 6 months, assessed in patients who received at least one dose of trastuzumab and pembrolizumab. The regimen would be considered worthy of further investigation if 26 or more of 37 patients were progression-free at 6 months. This trial is registered with ClinicalTrials.gov, NCT02954536, and is ongoing, but closed to enrolment. FINDINGS: Between Nov 11, 2016, and Jan 23, 2019, 37 patients were enrolled. At the time of data cutoff on Aug 6, 2019, median follow-up among survivors was 13·0 months (IQR 11·7-23·5). The primary endpoint was achieved; 26 (70%; 95% CI 54-83) of 37 patients were progression-free at 6 months. The most common treatment-related adverse event of any grade was neuropathy, which was reported in 36 (97%) of 37 patients. The most common grade 3 or 4 adverse events were lymphocytopenia (seven [19%] patients with grade 3 and two [5%] with grade 4), grade 3 decreased electrolytes (six [16%] patients), and grade 3 anaemia (four [11%] patients). Serious adverse events occurred in two patients patients (both grade 3 nephritis leading to treatment discontinuation). Four patients discontinued pembrolizumab because of immune-related adverse events. There were no treatment-related deaths. INTERPRETATION: Pembrolizumab can be safely combined with trastuzumab and chemotherapy and has promising activity in HER2-positive metastatic oesophagogastric cancer. A randomised phase 3 clinical trial assessing the efficacy and safety of pembrolizumab versus placebo in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric cancer is underway. FUNDING: Merck & Co.


Assuntos
Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/efeitos dos fármacos , Receptor ErbB-2/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/administração & dosagem , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Progressão da Doença , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/imunologia , Junção Esofagogástrica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Receptor ErbB-2/imunologia , Transdução de Sinais , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Trastuzumab/efeitos adversos , Adulto Jovem
18.
Surg Today ; 50(10): 1240-1248, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32451714

RESUMO

PURPOSE: Patients who receive trastuzumab (T-mab) plus chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer sometimes respond remarkably well and can undergo radical surgery. However, the clinical outcomes of preoperative T-mab combined chemotherapy with radical gastrectomy remain unclear. We conducted this study to investigate the clinical outcomes of this multimodal treatment. METHODS: From among a total of 199 patients who received T-mab-based chemotherapy for stage IV HER2-positive gastric or gastroesophageal junction cancer between 2011 and 2018, the subjects of this retrospective analysis were 20 patients who subsequently underwent radical gastrectomy. RESULTS: Seven patients had gastroesophageal junction cancer and 13 had gastric cancer. Eleven patients had unresectable stage IV cancer and 9 had resectable metastatic disease. Chemotherapy regimens included capecitabine, cisplatin + T-mab (11 patients), and S-1, oxaliplatin + T-mab (nine patients). The median number of chemotherapy cycles before surgery was three (range, 2-62). During preoperative chemotherapy, grade 3/4 adverse events developed in six patients. None suffered grade ≥ 3b postoperative complications. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 58.9% and 89.5%, respectively. CONCLUSION: Combined preoperative T-mab-based chemotherapy and surgery appears to be safe and effective for stage IV HER2-positive gastric or gastroesophageal junction cancer, with a clinically meaningful impact on RFS and OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica , Gastrectomia , Receptor ErbB-2 , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Trastuzumab/administração & dosagem , Adulto , Idoso , Terapia Combinada , Infecções por Coronavirus/tratamento farmacológico , Intervalo Livre de Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Estudos Retrospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto Jovem
19.
Breast Cancer Res ; 22(1): 54, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460816

RESUMO

INTRODUCTION: Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer. PATIENTS AND METHODS: In this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints. RESULTS: A total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6-44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4-24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group. CONCLUSIONS: Better clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01622361. Registration June 19, 2012.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfonodos/patologia , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Gosserrelina/administração & dosagem , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Pessoa de Meia-Idade , Pré-Menopausa , Prognóstico , Estudos Prospectivos , Receptores de Progesterona/metabolismo , Trastuzumab/administração & dosagem
20.
Anticancer Res ; 40(4): 2303-2309, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234930

RESUMO

BACKGROUND/AIM: To predict pCR during neoadjuvant chemotherapy is still difficult. The aim of this study was to evaluate the optimal tumor reduction rate and modalities for predicting pCR after two cycles of docetaxel. PATIENTS AND METHODS: We analyzed 52 patients with HER2-positive or triple-negative breast cancer. The tumor reduction rate was evaluated after two 3-week cycles of docetaxel (plus trastuzumab for HER2-positive cancer patients). Patients without progression completed two additional cycles of docetaxel and four cycles of an anthracycline-containing regimen. RESULTS: Twenty-eight patients achieved pCR. The optimal tumor reduction rates for predicting pCR were 23, 39, 32, and 40% for US, caliper, MMG, and MRI measurements, respectively. The AUC was highest for caliper measurements. The optimal modality for predicting pCR differed among subtypes. CONCLUSION: Although tumor reduction rate after two cycles of chemotherapy is highly predictive of pCR, the optimal cutoff value differed among the modalities and breast cancer subtype.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Mama/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Antraciclinas/administração & dosagem , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/metabolismo , Docetaxel/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Indução de Remissão , Trastuzumab/administração & dosagem , Carga Tumoral/efeitos dos fármacos , Ultrassonografia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...