RESUMO
BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.
Assuntos
Bevacizumab , Neoplasias da Mama , Neoplasias Colorretais , Hipertensão , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Hipertensão/induzido quimicamente , Estudos Prospectivos , Idoso , Masculino , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Metilação de DNARESUMO
PURPOSE: HER2-targeted therapies have dramatically improved outcomes of patients with HER2-positive breast cancer (BC), as demonstrated in neoadjuvant trials. This study aims to provide real-world evidence on the use and effectiveness of combined pertuzumab, trastuzumab and chemotherapy (CT) in early-stage HER2-positive BC. METHODS: A retrospective, multicentre study was conducted on patients diagnosed with HER2-positive early BC treated with neoadjuvant pertuzumab and trastuzumab plus CT at 13 Spanish sites. The primary endpoint was pathological complete response (pCR). RESULTS: A total of 310 patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes, carboplatin and docetaxel, and taxane-based CT in 77.1%, 16.5%, and 6.5% of patients, respectively. Overall, the pCR rate was 62.2%. The pCR was higher amongst patients with hormone receptor-negative tumours and with tumours expressing higher levels of Ki-67 (> 20%). After postoperative adjuvant treatment, 13.9% of patients relapsed. Those patients who did not achieve pCR, with tumours at advanced stages (III), and with node-positive disease were more likely to experience distant relapse. Median overall survival (OS) and distant disease-free survival (D-DFS) were not reached at the study end. The estimated mean OS and D-DFS times were 7.5 (95% CI 7.3-7.7) and 7.3 (95% CI 7.1-7.5) years, respectively (both were significantly longer amongst patients who achieved pCR). Grade 3-4 anti-HER2 related toxicities were reported in six (1.9%) patients. CONCLUSION: Neoadjuvant pertuzumab and trastuzumab plus CT achieve high pCR rates in real-life patients with HER2-positive early BC, showing an acceptable safety profile. Innovative adjuvant strategies are essential in patients at high risk of distant disease recurrence.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Trastuzumab/uso terapêutico , Trastuzumab/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Adulto , Idoso , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Estadiamento de NeoplasiasRESUMO
PURPOSE: To conduct a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) in women with node-positive breast cancer at diagnosis and node-negative tumour after neoadjuvant therapy, compared to axillary lymph-node dissection. METHODS: The more relevant databases were searched. Main outcomes were false-negative rate (FNR), sentinel lymph-node identification rate (SLNIR), negative predictive value (NPV), and accuracy. We conducted meta-analyses when appropriate. RESULTS: Twenty studies were included. The pooled FNR was 0.14 (95% CI 0.11-0.17), the pooled SLNIR was 0.89 (95% CI 0.86-0.92), NPV was 0.83 (95% CI 0.79-0.87), and summary accuracy was 0.92 (95% CI 0.90-0.94). SLNB performed better when more than one node was removed and double mapping was used. CONCLUSIONS: SLNB can be performed in women with a node-negative tumour after neoadjuvant therapy. It has a better performance when used with previous marking of the affected node and with double tracer.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/diagnóstico , Linfonodos/cirurgia , Linfonodos/patologia , Terapia Neoadjuvante , Axila , Biópsia de Linfonodo Sentinela , Excisão de LinfonodoRESUMO
BACKGROUND: We aimed to determine the effect of dual anti-HER2 blockade compared to monotherapy on clinically important outcomes. METHODS: We carried out a systematic review updated until July 2022. The outcomes included pathological complete response (pCR), clinical response, event-free survival, and overall survival. RESULTS: We identified eleven randomized clinical trials (2836 patients). When comparing paclitaxel plus dual treatment versus paclitaxel plus trastuzumab or lapatinib, dual treatment was associated with a higher probability of achieving a pathological complete response (OR 2.88, 95% CI 2.02-4.10). Addition of a taxane to an anthracycline plus cyclophosphamide and fluorouracil, plus lapatinib or trastuzumab, showed that the dual treatment was better than lapatinib alone (OR 2.47, 95% CI 1.41-4.34), or trastuzumab alone (OR 1.89, 95% CI 1.13-3.16). Dual treatment may result in an increase in survival outcomes and tumour clinical response, although such benefits are not consistent for all the combinations studied. CONCLUSIONS: The use of dual blockade with combinations of trastuzumab and pertuzumab can be recommended for the neoadjuvant treatment of women with HER2-positive breast cancer. PROSPERO Registration number: CRD42018110273.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Lapatinib/uso terapêutico , Terapia Neoadjuvante , Receptor ErbB-2/análise , Quinazolinas , Resultado do Tratamento , Trastuzumab/uso terapêutico , Paclitaxel , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
PURPOSE: We conducted a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) after the neoadjuvant chemotherapy, compared to axillary lymph-node dissection, in terms of false-negative rate (FNR) and sentinel lymph-node identification rate (SLNIR), sensitivity, negative predictive value (NPV), need for axillary lymph-node dissection (ALND), morbidity, preferences, and costs. METHODS: MEDLINE, Embase, Scopus, and The Cochrane Library were searched. We assessed the quality of the included systematic reviews using AMSTAR2 tool, and estimated the degree of overlapping of the individual studies on the included reviews. RESULTS: Six systematic reviews with variable quality were selected. We observed a very high overlapping degree across the included reviews. The FNR and the SLNIR were quite consistent (FNR 13-14%; SLNIR ~ 90% or higher). In women with initially clinically node-negative breast cancer, the FNR was better (6%), with similar SLNIR (96%). The included reviews did not consider the other prespecified outcomes. CONCLUSIONS: It would be reasonable to suggest performing an SLNB in patients treated with NACT, adjusting the procedure to the previous marking of the affected lymph node, using double tracer, and biopsy of at least three sentinel lymph nodes. More well-designed research is needed. PROSPERO registration number: CRD42020114403.
Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela/métodosRESUMO
INTRODUCTION: The identification and validation of biomarkers of chemotherapy sensitivity is critical in order to individualise therapy in breast cancer. We evaluated pathological complete response (pCR) to GAT, and its correlation with tumour biomarkers before and after neoadjuvant chemotherapy. MATERIALS AND METHODS: Stage III (and stage II with T≥5 cm) breast cancer patients were included. Treatment consisted of adriamycin (40 mg/m(2)) day 1, and paclitaxel (150 mg/ m(2)) followed by gemcitabine (2000 mg/m(2)) day 2, every 14 days for six cycles. Tissue from pre-treatment biopsy and surgery was evaluated for biologic markers by immunohistochemistry. Two XPD single nucleotide polymorphisms (SNP) were also analysed. RESULTS: Forty-six patients entered the trial. Median age was 49.5 years (range 31-72); 25 patients (54%) were pre-menopausal; 12 (26%) were ER-PgR-negative; pCR was observed in 17% (95% CI: 6.4-28.4) of patients. Significant differences in marker expression (mean±SD) in correlation to pathological response were only found in Ki- 67. After treatment, tumours showed lower Ki-67-, surviving- and pERK-positive cells. No correlation between XPD polymorphisms and pCR was found. The overall response rate was 89% (95% CI: 80.1-98.1). Fifteen patients (33%) underwent breast-conserving surgery. The most frequent grade 3 or 4 toxicities were neutropenia (with one febrile neutropenia) and asthenia. CONCLUSION: These results show an effective regimen with acceptable tolerability. Our data suggest that not only classical markers (ER, Ki-67), but also survivin and pERK could be involved in the response to GAT, which may contribute to therapy individualisation in future study designs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Antígeno Ki-67/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/administração & dosagem , Polimorfismo de Nucleotídeo Único , Survivina , GencitabinaRESUMO
INTRODUCTION: In breast cancer, the metastatic process may involve the dissemination of circulating tumour cells (CTCs) through the blood and lymphatic system prior to the colonisation of distant organs. Here we demonstrate the predictive capacity of CTCs for detecting risk of death in breast cancer patients during established time intervals. METHODS: CTCs were identified by immunocytochemical methods following isolation by selective immunomagnetic cell separation of cytokeratin-positive cells. Serial blood samples from 65 patients were collected at roughly monthly intervals for up to 50 months. Follow-up was conducted at different intervals: 1-5, >5-12, >12-24 and >24-50 months. RESULTS: Both presence and number of CTCs were correlated to risk of death: patients with CTCs at any time during follow-up had a higher risk of death (p=0.035) than patients without CTCs. Furthermore, during the first 5 months of therapy, patients with >5 CTCs had a higher risk of death than patients with <5 CTCs (p=0.002). CONCLUSIONS: Our results show that the persistence of CTCs after chemotherapy, particularly during the first 5 months, could define a group of patients with a high risk of relapse.
Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/tratamento farmacológico , Separação Celular , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , PrognósticoRESUMO
The incidence is increasing due to mammographic screening and an ageing population. In some countries the mortality rate has decreased especially in middleaged and younger groups because of improved treatment and possibly earlier detection. However, breast cancer is still the leading cause of cancer-related death in European women. The purpose of this work was to elaborate a Spanish Society of Medical Oncology guideline on pharmacologic interventions for early breast cancer (BC). We have compiled the latest advances in the management of this pathology either in the adjuvant and neoadjuvant setting, cytostatic and hormonal treatment, so that in a simple way could be useful to oncologist, residents and other related specialties.
Assuntos
Neoplasias da Mama/terapia , Carcinoma/terapia , Oncologia/métodos , Guias de Prática Clínica como Assunto , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma/patologia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Humanos , Oncologia/legislação & jurisprudência , Sociedades Médicas , EspanhaRESUMO
The distant growth of tumour cells escaping from primary tumours, a process termed metastasis, represents the leading cause of death among patients affected by malignant neoplasias from breast and colon. During the metastasis process, cancer cells liberated from primary tumour tissue, also termed circulating tumour cells (CTCs), travel through the circulatory and/or lymphatic systems to reach distant organs. The early detection and the genotypic and phenotypic characterisation of such CTCs could represent a powerful diagnostic tool of the disease, and could also be considered an important predictive and prognostic marker of disease progression and treatment response. In this article we discuss the potential relevance in the clinic of monitoring CTCs from patients suffering from solid epithelial tumours, with emphasis on the impact of such analyses as a predictive marker for treatment response.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias/tratamento farmacológico , Células Neoplásicas Circulantes/química , PrognósticoRESUMO
PURPOSE: To study the role of breast cancer molecular subtypes according to hormone receptors and HER2 status as a predictive factor for pathological complete response (pCR) to neoadjuvant chemotherapy. PATIENTS AND METHODS: Eligible patients received one of the two chemotherapy schedules every two weeks with prophylactic growth factor support; schedule A: epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2 d1 for 3 cycles followed by a second sequence with paclitaxel (P) 150 mg/ m2-gemcitabine (G) 2500 mg/m2 d1+/-trastuzumab (T) 2 mg/kg/week according to HER2 status (n=73); schedule B: adriamycin (40 mg/m2) d1 plus P (150 mg/m2)-G (2000 mg/m2) d2 for 6 cycles (n=54). Subsequently, patients underwent surgery, radiotherapy and/or adjuvant hormonal therapy according to standard practice. RESULTS: A total of 127 patients were evaluated. Forty-three patients (33.9%) achieved a pCR (50% in patients with HER2+tumours treated with T). Patients treated with che - motherapy alone (n=107, 18 HER2+) had a pCR of 32% (p=0.068). The pCR rate for patients with triple negative (HR and HER2-) cancers was 58.3%, 39.5% for HER2+ and 5.4% for ER/PR+ and HER2- (p<0.001). No differences in disease-free survival (DFS) were noted as a function of pCR, HER2 and HR status or treatment received (+/-T). However, statistical differences in DFS were observed as a function of whether patients had + or - axillar lymph nodes. Patients with + lymph node disease did worse (3 years DFS of 53.7% vs. 81.5%, p=0.025). Breast-conserving surgery was performed in 77 patients (60.6%). CONCLUSION: Tumour molecular subtyping defines different pCR to neoadjuvant chemotherapy (NC) but has no impact over DFS in patients with LABC. Although no significant correlation between HER2 status and trastuzumab therapy with pCR was found, probably due to the small number of patients, a favourable trend was observed in the group of HER2+ tumours treated with T.