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1.
Anticancer Res ; 41(10): 5007-5014, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593449

RESUMO

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Furanos/administração & dosagem , Humanos , Cetonas/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Retratamento , Taxa de Sobrevida
2.
Gan To Kagaku Ryoho ; 48(10): 1251-1254, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34657057

RESUMO

Palbociclib, a CDK4/6 inhibitor, is found to be an effective therapeutic drug in the treatment of estrogen receptor positive (ER+)metastatic breast cancer. In this report, we describe a case of rapid progression of life-threatening multiple bone metastases of breast cancer treated with a combination of fulvestrant and palbociclib. The patient, a 58-year-old postmenopausal woman, was diagnosed with left breast cancer at the age of 43 years and underwent breast-conserving surgery. After the completion of postoperative adjuvant endocrine therapy and radiotherapy, the patient was placed on regular follow-up. Eleven years after the surgery, multiple bone metastases and multiple lymph node metastases occurred, and the patient was treated with letrozole as first-line therapy for recurrent breast cancer. Although she continued to receive this treatment for 2 years and 10 months, her general condition worsened due to the occurrence of new liver metastases and the rapid progression of existing metastatic lesions. Thus, she was sent to an emergency room. Marked hypercalcemia and a severe decrease in erythrocyte and platelet counts were observed, which could be the cause of her worsening general condition. Her performance status(PS)was 4, and palliative treatment was also considered. However, she received treatment for hypercalcemia and red blood cell transfusion; as a result, she recovered to the PS 2 where she could begin chemotherapy. Then, she began a treatment consisting of a combination of fulvestrant and palbociclib as a second-line treatment for the recurrence. The patient responded well to the treatment, and her general condition improved to PS 1. She has since maintained a good quality of life for 2 years and 11 months without serious adverse events. In conclusion, the combination of fulvestrant and palbociclib has a low risk of serious adverse events and is a worthwhile treatment for rapidly progressing, life-threatening multiple bone metastases of breast cancer.


Assuntos
Neoplasias da Mama , Receptores de Estrogênio , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Fulvestranto/uso terapêutico , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Piperazinas , Piridinas , Qualidade de Vida , Receptor ErbB-2
4.
Rev Assoc Med Bras (1992) ; 67(8): 1167-1171, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34669864

RESUMO

OBJECTIVE: To explore the values of automated breast volume scanning (ABVS) combined with shear wave elastography (SWE) in the differential diagnosis of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-positive breast cancers (HER2+BC). METHODS: In this study, 28 patients with TNBC and 32 patients with HER2+BC were enrolled. The characteristics of ABVS and virtual touch quantification (VTQ) in SWE of all patients were reviewed. The multivariate logistic regression analysis was carried out and the receiver operating characteristic curves of ABVS and ABVS+VTQ were drawn. RESULTS: In ABVS imaging, the microcalcification, posterior echo, internal echo, shape, and edge had significant difference between TNBC and HER2+BC groups (p<0.05). The regular shape was the independent factor for TNBC (p=0.04, odds ratio [OR]=4.479), and the microcalcification in mass was the independent factor for HER2+BC (p=0.01, OR=2.997). In VTQ imaging, the shear wave velocity (SWV)max, SWVmin, and SWVmean in TNBC group were significantly lower than those in HER2+BC group (p<0.001). The sensitivity, specificity, and accuracy of ABVS+VTQ in diagnosing TNBC were higher than those of ABVS alone. CONCLUSIONS: ABVS combined with SWE has certain advantages in differentiating TNBC from HER2+BC, which is helpful for the treatment planning and prognosis judgment.


Assuntos
Neoplasias da Mama , Técnicas de Imagem por Elasticidade , Neoplasias de Mama Triplo Negativas , Mama , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Curva ROC , Receptor ErbB-2 , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem
5.
J Int Med Res ; 49(10): 300060520967774, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34666529

RESUMO

OBJECTIVES: To investigate the relationship between high-molecular-weight cytokeratin (34ßE12) and clinicopathological parameters (including HER-2, Ki67 and steroid receptors) in breast cancer to determine its usefulness as a prognostic marker. METHODS: In this retrospective study, the expression level 34ßE12 was assessed in surgically resected breast cancer specimens by immunohistochemical staining. Data were correlated with the patients' clinicopathological parameters. RESULTS: Of the 348 breast cancer tissue samples, 232 (67%) showed positive expression of 34ßE12. There were statistically significant differences between the positive and negative 34ßE12 expression groups in tumour size, lymph node involvement, oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status. There were no differences between groups in age, tumour grade, or Ki67 status. In addition, patients who were positive for 34ßE12 had significantly extended overall survival. In multivariate analysis, the expression level of 34ßE12 was found to be a significant independent prognostic factor. CONCLUSION: These results suggest that positive 34ßE12 expression is associated with a favourable outcome in breast cancer and so may be a useful prognostic factor. Further studies are required to confirm these results.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Antígeno Ki-67/genética , Prognóstico , Receptor ErbB-2/genética , Receptores de Estrogênio , Receptores de Progesterona/genética , Estudos Retrospectivos
6.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479891

RESUMO

Ado-trastuzumab emtansine (T-DM1) is a monoclonal antibody drug conjugate approved for the treatment of HER2-positive breast cancers. Presented here is a case report of a patient who developed fatal pulmonary toxicity in the form of acute eosinophilic pneumonia while undergoing treatment with T-DM1. Prior to beginning T-DM1 therapy, this patient had been treated with two HER2-targeted agents (trastuzumab, pertuzumab) per National Comprehensive Cancer Network (NCCN) guidelines. This case represents a novel presentation of toxicity associated with T-DM1 while perhaps demonstrating additive toxicity associated with multiple lines of HER2 targeted therapies.


Assuntos
Neoplasias da Mama , Maitansina , Eosinofilia Pulmonar , Ado-Trastuzumab Emtansina , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Maitansina/efeitos adversos , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/diagnóstico , Receptor ErbB-2 , Trastuzumab/efeitos adversos
7.
Anticancer Res ; 41(9): 4619-4627, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475090

RESUMO

BACKGROUND: The real-world outcomes of patients with advanced invasive lobular carcinoma (ILC) of the breast are unclear because of its rarity. PATIENTS AND METHODS: We identified 435 patients with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer treated at our Institute between 2002 and 2019, and analyzed their outcomes retrospectively. RESULTS: We identified 29 patients with advanced ILC. At presentation, they had a lower rate of lung metastasis (p=0.0053) but a higher rate of stomach metastasis (p=0.0379) compared with other patients with advanced breast cancer. Median overall survival did not differ; however, multivariate analyses showed that ILC histopathology was a risk factor for poorer overall survival (hazard ratio=3.43, p=0.0038) in patients with de novo stage IV ER+ HER2- breast cancer. Patients with ILC showed a markedly different patten of subsequent metastasis, such as less in the lung and more in the stomach, leptomeninges, and bone marrow. CONCLUSION: According to our retrospective study, in patients with de novo stage IV ER+ HER2- breast cancer, ILC histopathology was associated with increased risk of death.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
9.
Mayo Clin Proc ; 96(9): 2498-2499, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34481607
10.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34551980

RESUMO

As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins. However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation. To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein. The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone. The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency. The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification. Structural models suggested that affinity was improved by creating novel interfacial contacts with a glycan at the periphery of a protein-protein interface. Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.


Assuntos
Asparagina/química , Proteínas de Transporte/metabolismo , Proteínas de Escherichia coli/metabolismo , Glicoproteínas/metabolismo , Polissacarídeos/metabolismo , Processamento de Proteína Pós-Traducional , Ribonuclease Pancreático/metabolismo , Anticorpos de Cadeia Única/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Transporte/química , Proteínas de Transporte/genética , Bovinos , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Glicoproteínas/química , Glicoproteínas/genética , Glicosilação , Humanos , Polissacarídeos/química , Polissacarídeos/genética , Conformação Proteica , Engenharia de Proteínas , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/imunologia , Ribonuclease Pancreático/química , Ribonuclease Pancreático/genética , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética
11.
Cesk Patol ; 57(3): 161-166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34551565

RESUMO

Evaluation of tumor infiltrating lymphocytes (TIL) is gaining importance in many cancers not only because of their prognostic, but also predictive significance. One of the tumors in which the evaluation of TIL is of prognostic importance and has potential predictive impact on the modification of treatment procedures is breast cancer, especially its so-called triple negative, and HER2 positive variants.The aim of this review is to provide an overview of the issue of TIL evaluation in breast cancer, focusing not only on the clinical significance of this evaluation, but especially on the methodological aspects of evaluation and standardized reporting of the results.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Linfócitos do Interstício Tumoral , Prognóstico , Receptor ErbB-2
12.
Breast Cancer Res Treat ; 189(3): 665-676, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34553296

RESUMO

PURPOSE: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. METHODS: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. RESULTS: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity. CONCLUSION: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. CLINICAL TRIAL REGISTRATION: NCT01808573.


Assuntos
Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Capecitabina/uso terapêutico , Feminino , Humanos , Lapatinib/uso terapêutico , Quinolinas , Receptor ErbB-2/genética , Resultado do Tratamento
13.
Int J Pharm ; 608: 121081, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34506924

RESUMO

Human epidermal growth factor receptor 2 (HER2) is overexpressed in some breast and gastric cancer patients. As the first HER2-targeteed therpeutic antibody, trastuzumab could significantly improve the prognosis of HER2-positive cancer patients. However, even responding patients inevitably get worse due to acquired resistance to trastuzumab after a period of treatment. Many HER2-targeted antibody drugs used wild-type tumor cells to conduct their corresponding preclinical experiments in vitro and in vivo. However, it is impossible to determine whether these newly developed drugs have antitumor effective to trastuzumab-resistant tumor cells. In the study, two trastuzumab-resistant HER2-positive tumor cell populations NCI-N87-TR and BT474-TR were generated. Then, we examined the anti-tumor effects of newly constructed immunotoxins with low immunogenicity and off-target toxicity based on the trastuzumab-resistant tumor cells both in vitro and in vivo. Results demonstrated that the immunotoxin IHP25-BT could not only effectively inhibit tumor growth but also inhibit liver metastasis of tumor cells in a mouse xenograft model. Furthermore, tumor tissue transcriptome sequencing was performed to clarify the potential mechanisms of inhibiting tumor cell distant metastasis by immunotoxin. In conclusion, this work describes a series of attractive therapeutic immunotoxins, the low immunogenicity and off-target toxicity making them promising for trastuzumab-resistant cancer therapy.


Assuntos
Neoplasias da Mama , Imunotoxinas , Neoplasias Gástricas , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Receptor ErbB-2 , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto
16.
BMC Cancer ; 21(1): 1033, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530760

RESUMO

BACKGROUND: Standard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy. METHODS: This is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate. DISCUSSION: The addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04382300 . Registered on May 11, 2020.


Assuntos
Acrilamidas/administração & dosagem , Aminoquinolinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor ErbB-2/genética , Talidomida/administração & dosagem , Acrilamidas/efeitos adversos , Aminoquinolinas/efeitos adversos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , China , Diarreia/induzido quimicamente , Esquema de Medicação , Éxons , Humanos , Fator de Transcrição Ikaros/efeitos dos fármacos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2/antagonistas & inibidores
17.
Anal Chem ; 93(40): 13597-13605, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34582688

RESUMO

Trastuzumab and pertuzumab are monoclonal antibodies used in the treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Therapeutic proteins may undergo chemical modifications that may affect the results of bioanalytical assays, as well as their therapeutic efficacy. Modifications may arise during production and storage, as well as after administration to patients. Studying in vivo biotransformation of monoclonal, therapeutic antibodies requires their enrichment from plasma to discriminate them from endogenous antibodies, as well as from other plasma proteins. To this end, we screened Affimer reagents for selectivity toward trastuzumab or pertuzumab. Affimer reagents are alternative binding proteins possessing two variable binding loops that are based on the human protease inhibitor stefin A or phytocystatin protein scaffolds. Affimer reagents were selected from an extensive library by phage display. The four best-performing binders for each therapeutic antibody were prioritized using a microtiter plate-based approach combined with liquid chromatography-mass spectrometry (LC-MS) in the selected reaction monitoring (SRM) mode. These Affimer reagents were immobilized via engineered 6-His or Cys tags to Ni2+- or maleimide beads, respectively. Recovery values of 70% and higher were obtained for both trastuzumab and pertuzumab when spiked at 100, 150, and 200 µg/mL concentrations in human plasma followed by trypsin digestion in the presence of 0.5% sodium deoxycholate and 10 mM dithiothreitol (DTT). Notably, the maleimide beads showed undetectable unspecific binding to endogenous immunoglobulin G (IgGs) or other plasma proteins when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enrichment method was applied to samples from stress tests of the antibodies at 37 °C to mimic in vivo conditions.


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias da Mama , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Cromatografia Líquida , Feminino , Humanos , Indicadores e Reagentes , Espectrometria de Massas , Receptor ErbB-2 , Trastuzumab
18.
Oncol Res Treat ; 44(10): 557-567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515204

RESUMO

BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitors have been advocated for adjuvant therapy of metastatic hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- breast cancer (BC). However, the efficiency of adding CDK 4/6 inhibitors to neoadjuvant therapy was not unequivocal. OBJECTIVE: The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2- BC. METHOD: We searched PubMed, the Cochrane Library, Web of Science, and Embase online databases for randomized controlled trials and single-arm studies written in English until April 2021. RESULTS: Five studies comparing CDK 4/6 inhibitors + ET as neoadjuvant treatments to ET alone and 2 studies comparing neoadjuvant CDK 4/6 inhibitors + ET to neoadjuvant chemotherapy were analysed. Neoadjuvant CDK 4/6 inhibitors + ET improved the rate of complete cell cycle arrest (CCCA: central Ki67 < 2.7%, odds ratio [OR] = 7.91, 95% confidence interval [CI] = 4.81-13.03, p < 0.001), increased the risk of adverse events (AEs; especially ≥3 AEs; AEs of all grades: OR = 9.10, 95% CI = 2.39-34.58, p = 0.001; AEs ≥3: OR = 12.24, 95% CI = 4.17-35.88, p < 0.001), led to no significant differences in pathological complete response (pCR) in patients with BC (OR = 0.34, 95% CI = 0.04-2.85, p = 0.318) compared to endocrine monotherapy. Moreover, subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59-29.61, p < 0.001; palbociclib: OR = 7.39, 95% CI = 1.26-43.40, p = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41-20.11, p < 0.001). Compared to neoadjuvant chemotherapy, neoadjuvant CDK 4/6 inhibitors plus ET decreased the risk of AEs ≥3 (OR = 0.50, 95% CI = 0.29-0.87, p = 0.015) and showed similar ability to reach pCR (OR = 0.50, 95% CI = 0.12-2.07, p = 0.342) and reduce the residual cancer burden (RCB, RCB 0-1: OR = 0.47, 95% CI = 0.18-1.22, p = 0.121; RCB 2-3: OR = 2.30, 95% CI = 0.89-5.91, p = 0.084). CONCLUSIONS: The results suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina/uso terapêutico , Quinase 6 Dependente de Ciclina , Feminino , Humanos , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2
19.
Breast Cancer Res Treat ; 189(3): 653-663, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34487293

RESUMO

PURPOSE: To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)-expressing invasive breast cancer. METHODS: This retrospective, non-interventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathological characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-low (1% to 10%) and ER-high (> 10%) according to the Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test. RESULTS: 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-low tumors: 63 (53.8%) of whom had HER2- tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-high/HER2- cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-low/HER2- (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS. CONCLUSION: Patients with ER-low/HER2- breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-low/HER2- disease.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Prevalência , Prognóstico , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , República da Coreia/epidemiologia , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia
20.
Drugs Today (Barc) ; 57(9): 551-558, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586103

RESUMO

Up to 20% of breast cancers overexpress HER2, a molecular alteration conferring these tumors a particularly aggressive behavior. However, targeting HER2 has radically changed the prognosis of this disease in the last 2 decades, with multiple anti-HER2 compounds shown to improve disease outcomes both in the early and advanced setting. The latest anti-HER2 compound to be approved by the U.S. Food and Drug Administration (FDA) was margetuximab, an Fc-engineered monoclonal antibody with an improved binding to FcγRIIIA receptor, which leads to a greater antibody-dependent cellular cytotoxicity (ADCC) activation compared with trastuzumab. Margetuximab was shown to slightly improve progression-free survival compared with trastuzumab when combined with chemotherapy for the treatment of advanced HER2-positive breast cancer patients, and is now included among the available treatment options for pretreated HER2-positive breast cancer patients. In this monograph we recapitulate the clinical development, current role and future perspectives of margetuximab for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Receptor ErbB-2 , Trastuzumab
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