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1.
Nat Rev Dis Primers ; 5(1): 66, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548545

RESUMO

Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70-80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.

2.
Curr Opin Oncol ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31464762

RESUMO

PURPOSE OF REVIEW: Window of Opportunity (WOO) studies have gain their place in current clinical and translational research in breast cancer patients. This review provides current information and future applications of this specific type of research. RECENT FINDINGS: So far, WOO trials in breast cancer patients have demonstrated their utility in breast cancer research as: first they allow administering a treatment for a short period of time to treatment-naïve patients whose tumors have not developed mechanisms of resistance or heterogeneity because of previous therapies. Second, it brings a unique opportunity for translational research providing easy access to tumor tissue in order to evaluate antitumor effect from initial biopsy and from surgical resection specimen. They provide the perfect scenario for biomarker discovery and validation in an efficient and timely manner and valuable information about drug pharmacodynamics. Several issues need to be contemplated when designing and performing this type of trials including choice of a biological surrogate endpoint of efficacy as standard clinical activity endpoints are not feasible. SUMMARY: Despite some limitations like the absence of information about secondary mechanisms of resistance, WOO trials represent an important support for drug development and biomarker discovery in breast cancer patients.

3.
JAMA Oncol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31465093

RESUMO

Importance: Randomized clinical trials have demonstrated a substantial benefit of adding everolimus to endocrine therapy. Everolimus inhibits the mammalian target of rapamycin complex 1 (mTORC1) complex but not mTORC2, which can set off an activating feedback loop via mTORC2. Vistusertib, a dual inhibitor of mTORC1 and mTORC2, has demonstrated broad activity in preclinical breast cancer models, showing superior activity to everolimus. Objective: To evaluate the safety and efficacy of vistusertib in combination with fulvestrant compared with fulvestrant alone or fulvestrant plus everolimus in postmenopausal women with estrogen receptor-positive advanced or metastatic breast cancer. Design, Setting, and Participants: The MANTA trial is an open-label, phase 2 randomized clinical trial in which 333 patients with estrogen receptor-positive breast cancer progressing after prior aromatase inhibitor treatment underwent randomization (2:3:3:2) between April 1, 2014, and October 24, 2016, at 88 sites in 9 countries: 67 patients were assigned to receive fulvestrant, 103 fulvestrant plus vistusertib daily, 98 fulvestrant plus vistusertib intermittently, and 65 fulvestrant plus everolimus. Treatment was continued until disease progression, development of unacceptable toxic effects, or withdrawal of consent. Analysis was performed on an intention-to-treat basis. Interventions: Fulvestrant alone or in combination with vistusertib (continuous or intermittent dosing schedules) or everolimus. Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Results: Among the 333 women in the study (median age, 63 years [range, 56-70 years]), median PFS was 5.4 months (95% CI, 3.5-9.2 months) with fulvestrant, 7.6 months (95% CI, 5.9-9.4 months) with fulvestrant plus daily vistusertib, 8.0 months (95% CI, 5.6-9.9 months) with fulvestrant plus intermittent vistusertib, and 12.3 months (95% CI, 7.7-15.7 months) with fulvestrant plus everolimus. There was no significant difference in PFS between those receiving fulvestrant plus daily or intermittent vistusertib and fulvestrant alone (hazard ratio, 0.88 [95% CI, 0.63-1.24]; P = .46; and hazard ratio, 0.79 [95% CI, 0.55-1.12]; P = .16). Conclusions and Relevance: The combination of fulvestrant plus everolimus demonstrated significantly longer PFS compared with fulvestrant plus vistusertib or fulvestrant alone. The trial failed to demonstrate a benefit of adding the dual mTORC1 and mTORC2 inhibitor vistusertib to fulvestrant. Trial Registration: ClinicalTrials.gov identifier: NCT02216786 and EudraCT number: 2013-002403-34.

4.
Future Oncol ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31441323

RESUMO

Biosimilars are biologic products that are highly similar to, and have no clinically meaningful differences from, the approved originator molecule. They are poised to play an increasingly central role in cancer treatment, helping to improve access by driving down costs. Regulatory bodies have set out robust mechanisms for the approval of biosimilars, based on comprehensive and rigorous analytical and nonclinical comparisons with the originator. Product attributes (e.g., post-translational modifications) that are important to the function of the molecule must be similar between biosimilar and originator. This should be followed by a robust clinical development program, assessing pharmacokinetics, pharmacodynamics, efficacy, safety and immunogenicity. Equivalence in one indication might allow extrapolation across all the indications of the originator biologic. The recent approval of several trastuzumab biosimilars provides an example of how this process can work in practice for the benefit of patients, clinicians and payers.

5.
Clin Cancer Res ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439579

RESUMO

PURPOSE: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor. PATIENTS AND METHODS: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. RESULTS: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. CONCLUSIONS: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting.

6.
Eur J Cancer ; 120: 1-9, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445454

RESUMO

BACKGROUND: We assessed long-term cardiac safety and efficacy in patients with human epidermal growth factor receptor 2-positive early breast cancer treated with a trastuzumab biosimilar (SB3) or its reference product, trastuzumab (TRZ), in a phase 3 study. METHODS: Patients who completed the phase 3 study could be enrolled in this extension study. The outcomes included the incidence of symptomatic congestive heart failure (CHF), asymptomatic significant left ventricular ejection fraction (LVEF) decrease, incidence of other cardiac events, event-free survival (EFS), and overall survival. In post hoc analysis, the Cox proportional hazards regression model was used to assess factors associated with EFS. RESULTS: A total of 367 patients were enrolled in the study (SB3, n = 186; TRZ, n = 181). The median follow-up duration from the main study enrolment was 40.8 and 40.5 months for SB3 and TRZ, respectively. During the two-year follow-up after adjuvant therapy, incidence of asymptomatic significant LVEF decrease was rare (SB3, n = 1; TRZ, n = 2), with all patients recovering with LVEF ≥ 50%, and no cases of symptomatic CHF or other cardiac events were reported. At 3 years, the EFS was 91.9% with SB3 and 85.2% with TRZ. The number of patients with events was 17 (9.1%) with SB3 and 31 (17.1%) with TRZ [hazard ratio: 0.47, 95% confidence interval: 0.26-0.87]. Antibody-dependent cell-mediated cytotoxicity (ADCC) activity and the breast pathologic complete response rate were the factors associated with EFS. CONCLUSION: Cardiotoxicity was rare in this extension study. EFS was higher with SB3 versus TRZ, with post hoc analysis suggesting that a downward drift in ADCC activity was a contributing factor. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02771795 (EudraCT 2015-005663-17).

9.
J Atten Disord ; : 1087054719855685, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189374

RESUMO

Background: Attention-deficit/hyperactivity disorder (ADHD) is highly comorbid in adulthood. This meta-analysis was aimed at ascertaining the efficacy of different psychotherapies in improving comorbid internalizing symptoms in adults with ADHD. Method: Twenty randomized controlled trials and 12 uncontrolled pretest-posttest studies were included and combined using the inverse variance method. Risk of bias and heterogeneity assessment and moderator analyses were performed. Results: Cognitive-behavioral therapy (CBT) improved quality of life (QoL), emotional dysregulation (ED), depression, and anxiety symptoms, particularly at follow-up, which was predicted by core symptoms reduction. A significant between-group effect was obtained only on QoL, ED, and self-esteem for dialectical behavior therapy (DBT), mindfulness-based therapies (MBTs), and neurofeedback, respectively. Conclusion: Results support CBT efficacy for treating comorbid internalizing symptoms. More research is needed to determine the effectiveness of DBT, MBT, and neurofeedback. The small number of studies evaluating some therapies and the high risk of bias observed might limit these results.

10.
J Natl Cancer Inst ; 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31037288

RESUMO

BACKGROUND: Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. METHODS: A research-based PAM50 assay was applied in 422 HER2-positive tumors from 5 II-III clinical trials (SOLTI-PAMELA/TBCRC023/TBCRC006/PER-ELISA/EGF104090). In SOLTI-PAMELA, TBCRC023/TBCRC006 and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR) and overall survival (OS) were evaluated. RESULTS: 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E/ERBB2-high group showed a higher pCR rate compared to the rest (44.5% [95% CI = 35.4-53.9%] vs. 11.6% [95% CI = 6.9-18.0%]; adjusted odds ratio [OR]=6.05 [95%CI=3.10-11.80]; P<0.001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high [95% CI = 22.3-95.7%] vs. 14.7% in others [95% CI = 4.9-31.1%]; OR = 11.60, [95% CI 1.66-81.10]; p = 0.01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio=0.52 [95% CI = 0.35-0.79]; p < 0.001), higher ORR (16.3% [95% CI = 8.9-26.2%] vs. 3.7%; [95% CI = 0.8-10.3%]; p = 0.02) and longer OS (hazard ratio=0.66 [95% CI = 0.44-0.97]; p = 0.01). CONCLUSIONS: Combining HER2-E subtype and ERBB2 mRNA into single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in ∼40% of patients with HER2-positive breast cancer.

11.
Aging (Albany NY) ; 11(9): 2874-2888, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31076561

RESUMO

Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the "drug plus diet" approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients. A panel of 11 serum metabolites including markers of mitochondrial function and intermediates/products of folate-dependent one-carbon metabolism were measured in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. Metabolite profiles revealed a significant increase of the ketone body ß-hydroxybutyrate and of the TCA intermediate α-ketoglutarate in the metformin-containing arm. A significant relationship was found between the follow-up levels of homocysteine and the ability of treatment arms to achieve a pathological complete response (pCR). In the metformin-containing arm, patients with significant elevations of homocysteine tended to have a higher probability of pCR. The addition of metformin to an established anti-cancer therapeutic regimen causes a fasting-mimicking modification of systemic host metabolism. Circulating homocysteine could be explored as a clinical pharmacodynamic biomarker linking the antifolate-like activity of metformin and biological tumor response.

12.
Cell Rep ; 27(9): 2690-2708.e10, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141692

RESUMO

The detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer.

13.
Expert Opin Drug Saf ; 18(5): 347-355, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31107111

RESUMO

Introduction: Eribulin mesylate is a highly potent anticancer agent approved for use in pretreated metastatic breast cancer (MBC). Clinical trials of eribulin in MBC have demonstrated activity against this tumor type, and a phase 3 study in patients with MBC previously treated with an anthracycline and a taxane showed a significant increase in overall survival (OS) with eribulin versus control regimens. Areas covered: This review presents overviews of the development of eribulin, its pharmacology, and its efficacy in MBC. A detailed review of its safety profile is presented, and the safety of eribulin is compared with other agents commonly used to treat MBC. Expert opinion: As eribulin is the only drug shown to improve OS in patients with pretreated MBC, it is an important treatment option for many patients. Eribulin is currently considered a second-line (Europe) or third-line (United States) therapy, and studies have been examining use in the first-line setting. The use of eribulin in combination with other therapies is beginning to be explored because its manageable safety profile makes it an ideal combination-treatment partner. Emerging eribulin combination-treatment data suggest a manageable toxicity profile, and eribulin is set to be a key drug for the treatment of MBC in the future.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Furanos/efeitos adversos , Cetonas/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Feminino , Furanos/administração & dosagem , Furanos/farmacologia , Humanos , Cetonas/administração & dosagem , Cetonas/farmacologia , Metástase Neoplásica , Taxa de Sobrevida
14.
Future Oncol ; 15(19): 2211-2225, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074641

RESUMO

The increasing incidence of breast cancer brain metastases is a major clinical problem with its associated poor prognosis and limited treatment options. The long-acting topoisomerase-1 inhibitor, etirinotecan pegol, was designed to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Motivated by improved survival findings from subgroup analyses from the Phase III BEACON trial, this ongoing randomized, Phase III trial compares etirinotecan pegol to drugs commonly used for advanced breast cancer in patients with stable, treated breast cancer brain metastases who have been previously treated with an anthracycline, taxane and capecitabine. The primary end point is overall survival. Secondary end points include objective response rate, progression-free survival and time to CNS disease progression or recurrence in patients with/without CNS lesions present at study entry. Trial registration number: NCT02915744.

15.
Future Oncol ; 15(17): 1951-1961, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977385

RESUMO

The PD-L1 inhibitor atezolizumab received US FDA accelerated approval as treatment for PD-L1-positive metastatic triple-negative breast cancer (TNBC). In IMpassion130, combining atezolizumab with first-line nab-paclitaxel for metastatic TNBC significantly improved progression-free survival and showed a clinically meaningful effect on overall survival in patients with PD-L1-positive tumors. The placebo-controlled randomized Phase III IMpassion132 (NCT03371017) trial is evaluating atezolizumab with first-line chemotherapy (capecitabine [mandatory in platinum-pretreated patients] or gemcitabine/carboplatin) for inoperable locally advanced/metastatic TNBC recurring ≤12 months after completing standard (neo)adjuvant anthracycline and taxane chemotherapy. Stratification factors are: visceral metastases, tumor immune cell PD-L1 status and selected chemotherapy. Patients are randomized to atezolizumab 1200 mg or placebo every 3 weeks with the chosen chemotherapy, continued until progression, unacceptable toxicity or withdrawal. The primary end point is overall survival.

16.
Int J Mol Sci ; 20(5)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30832287

RESUMO

The combination of hydrodynamic and electrophoretic experiments and computer simulations is a powerful approach to study the interaction between proteins. In this work, we present hydrodynamic and electrophoretic experiments in an aqueous solution along with molecular dynamics and hydrodynamic modeling to monitor and compute biophysical properties of the interactions between the extracellular domain of the HER2 protein (eHER2) and the monoclonal antibody trastuzumab (TZM). The importance of this system relies on the fact that the overexpression of HER2 protein is related with the poor prognosis breast cancers (HER2++ positives), while the TZM is a monoclonal antibody for the treatment of this cancer. We have found and characterized two different complexes between the TZM and eHER2 proteins (1:1 and 1:2 TZM:eHER2 complexes). The conformational features of these complexes regulate their hydrodynamic and electrostatic properties. Thus, the results indicate a high degree of molecular flexibility in the systems that ultimately leads to higher values of the intrinsic viscosity, as well as lower values of diffusion coefficient than those expected for simple globular proteins. A highly asymmetric charge distribution is detected for the monovalent complex (1:1 complex), which has strong implications in correlations between the experimental electrophoretic mobility and the modeled net charge. In order to understand the dynamics of these systems and the role of the specific domains involved, it is essential to find biophysical correlations between dynamics, macroscopic transport and electrostatic properties. The results should be of general interest for researchers working in this area.


Assuntos
Antineoplásicos Imunológicos/química , Simulação de Acoplamento Molecular , Receptor ErbB-2/química , Trastuzumab/química , Antineoplásicos Imunológicos/farmacologia , Sítios de Ligação , Humanos , Hidrodinâmica , Ligação Proteica , Receptor ErbB-2/metabolismo , Eletricidade Estática , Trastuzumab/farmacologia
17.
Clin Breast Cancer ; 19(2): 105-112, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30679100

RESUMO

BACKGROUND: Eribulin has efficacy in patients with progression after ≥ 1 chemotherapeutic regimen for metastatic breast cancer (MBC). A short disease-free interval (DFI) and previous use of taxanes in the neoadjuvant or adjuvant setting have been associated with worse outcomes for patients receiving first-line chemotherapy for HER2-negative MBC. The aim of the present trial was to evaluate the efficacy and safety of eribulin as first-line therapy for patients with HER2-negative MBC with these poor prognostic factors. PATIENTS AND METHODS: Eribulin monotherapy was administered until disease progression or unacceptable toxicity. The principal selection criteria were HER2 negativity without previous chemotherapy for MBC, the previous use of taxanes for early-stage breast cancer, and a DFI of < 36 months (subsequently amended to 48 months). The primary endpoint was the investigator-assessed time to progression. The secondary endpoints included overall survival, progression-free survival, objective response rate, clinical benefit rate, duration of response, and toxicity profile. A total of 53 patients were enrolled and received ≥ 1 dose of eribulin. RESULTS: The median patient age was 47 years (range, 23-82.8 years). The median DFI was 15.7 months (range, 0.1-46.4 months). The median investigator-assessed time to progression was 4.1 months (range, 0.2-27.8 months; 95% confidence interval, 3.2-6.2 months). The objective response and clinical benefit rate was 20.8% and 26.4%, respectively. All-grade and grade 3/4 adverse events developed in 96.2% and 69.8% of patients, respectively. The most common treatment-related adverse events were neutropenia, leukopenia, alopecia, nausea, and anemia. CONCLUSION: Eribulin is effective and safe as first-line therapy for aggressive taxane-pretreated HER2-negative MBC.

18.
Genome Med ; 11(1): 1, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30609936

RESUMO

Circulating tumour DNA (ctDNA) detection and monitoring have enormous potential clinical utility in oncology. We describe here a fast, flexible and cost-effective method to profile multiple genes simultaneously in low input cell-free DNA (cfDNA): Next Generation-Targeted Amplicon Sequencing (NG-TAS). We designed a panel of 377 amplicons spanning 20 cancer genes and tested the NG-TAS pipeline using cell-free DNA from two HapMap lymphoblastoid cell lines. NG-TAS consistently detected mutations in cfDNA when mutation allele fraction was > 1%. We applied NG-TAS to a clinical cohort of metastatic breast cancer patients, demonstrating its potential in monitoring the disease. The computational pipeline is available at https://github.com/cclab-brca/NGTAS_pipeline .


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Software , Biomarcadores Tumorais/sangue , Linhagem Celular Tumoral , DNA Tumoral Circulante/sangue , Custos e Análise de Custo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/economia , Humanos , Mutação , Análise de Sequência de DNA/economia
19.
Oncologist ; 24(8): 1041-1047, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30578311

RESUMO

BACKGROUND: Data on the efficacy of chemotherapy regimens in patients with advanced invasive lobular carcinoma (ILC) of the breast are limited. We investigated the efficacy of single-agent eribulin for the treatment of advanced ILC when compared with invasive ductal carcinoma (IDC). PATIENTS AND METHODS: Results from the eribulin arms of two phase III studies (305 [EMBRACE] and 301) and a single-arm, phase II study were pooled. The studies involved patients with metastatic breast cancer who had previously received treatment with an anthracycline and a taxane. In all three studies, the dose of eribulin mesylate was 1.4 mg/m2 given on days 1 and 8 of a 21-day cycle. Overall survival (OS), progression-free survival (PFS), and response rates in patients with ILC were assessed and compared with data from patients with IDC. RESULTS: In total, 1,152 patients were included in this analysis (118 patients with ILC and 1,034 patients with IDC). Median OS was similar in patients with ILC and IDC (13.4 vs. 13.5 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.87-1.38); as was median PFS (4.1 vs. 3.6 months; HR, 0.91; 95% CI, 0.72-1.14). There were no major differences in response rates between the two groups. CONCLUSION: This retrospective analysis suggests that eribulin demonstrates similar efficacy in patients with ILC and IDC with metastatic disease who have previously received an anthracycline and a taxane. IMPLICATIONS FOR PRACTICE: Data on the efficacy of chemotherapy regimens in patients with advanced invasive lobular carcinoma (ILC) of the breast are limited. This pooled retrospective analysis of three clinical studies demonstrates that the magnitude of benefit of eribulin in the metastatic setting did not differ between patients with ILC versus invasive ductal carcinoma (IDC), even when restricting for patients with estrogen receptor-positive/HER2-negative IDC.

20.
Prog. obstet. ginecol. (Ed. impr.) ; 61(6): 540-544, nov.-dic. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-181387

RESUMO

Based on a multidisciplinary approach, the present statement proposes improvements and solutions for the primary prevention (vaccination against human papillomavirus) and secondary prevention (screening, early diagnosis) of cervical cancer in Spain


Desde una aproximación multidisciplinar, se describe la situación muy mejorable de la prevención primaria (vacunación frente a papiloma virus) y secundaria (cribado, diagnóstico precoz asistencial) del cáncer de cuello de útero en España y se aportan propuestas de solución y mejora


Assuntos
Humanos , Feminino , Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer/métodos , Vacinas contra Papillomavirus/administração & dosagem , Infecções por Papillomavirus/prevenção & controle , Melhoria de Qualidade/tendências , Programas de Rastreamento/métodos , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia
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