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Background: Eribulin shows some activity in controlling brain metastasis in breast cancer. Methods: This observational, multicenter study evaluated brain disease control rates, survival and safety in patients with brain metastatic breast cancer treated with eribulin in clinical practice. Results: A total of 34 patients were enrolled (mean age 49 years, 91% with visceral metastases) and 29 were evaluable for brain disease. Fourteen achieved disease control and showed a longer time without progression: 10 months (95% CI: 2.3-17.7) versus 4 months (95% CI: 3.3-4.7) in the control group (p = 0.029). Patients with clinical benefits at 6 months had longer survival. Leukopenia and neutropenia were the most frequent grade 3-4 toxicities. Conclusion: Eribulin confirms its effectiveness in patients with brain metastatic breast cancer. Further studies on larger cohorts are needed to confirm the results.
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Neoplasias Encefálicas/mortalidade , Neoplasias da Mama/mortalidade , Furanos/uso terapêutico , Cetonas/uso terapêutico , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. METHODS: The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. RESULTS: A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P < 0.001). Five-year DDFS according to prognostic stage was as follows: IA 95.7%, IB 91.4%, IIA 86.9%, IIB 85.0%, IIIA 77.6%, IIIC 67.7% (P < 0.001). The C index was similar (0.69209 and 0.69249, P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). CONCLUSIONS: The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. TRIAL REGISTRATION: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.
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Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/diagnóstico , Genes erbB-2 , Estadiamento de Neoplasias , Trastuzumab/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , PrognósticoRESUMO
Although Ki67 index suffers from poor reproducibility, it is one of the most important prognostic markers used by oncologists to select the treatment of estrogen receptor (ER) positive breast cancer patients. In this study, we aim to establish the optimal Ki67 cut-offs for stratifying patient prognosis and to create a comprehensive prognostic index for clinical applications. A mono-institutional cohort of 1.577 human epidermal growth factor receptor 2 negative/ER+ breast cancer patients having complete clinical, histological, and follow-up data was collected. The 14 and 20 % Ki67 cut-offs were correlated to disease-free interval (DFI) and disease-specific survival (DSS). To create a comprehensive prognostic index, we used independent variables selected by uni/multivariate analyses. In terms of DFI and DSS, patients bearing tumors with Ki67 < 14 % proliferation index did not differ from those with Ki67 values between 14 and 20 %. Patients with tumor with Ki67 > 20 % showed the poorest prognosis. Moreover, to tumor size, the number of metastatic lymph nodes and Ki67 > 20 % was given a score value, varying depending on definite cut-offs and used to create a prognostic index, which was applied to the population. Patients with a prognostic index ≥3 were characterized by significant risk of relapse [DFI: Hazard Ratio (HR) = 4.74, p < 0.001] and death (DSS: HR = 5.03, p < 0.001). We confirm that the 20 % Ki67 cut-off is the best to stratify high-risk patients in luminal breast cancers, and we suggest to integrate it with other prognostic factors, to better stratify patients at risk of adverse outcome.
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Neoplasias da Mama/metabolismo , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Adulto JovemRESUMO
Anthracyclines are among the most active drugs in breast cancer. Because of excessive cardiotoxicity, their use in combination with trastuzumab has been discouraged in patients with human epidermal growth factor receptor (HER)-2(+) metastatic breast cancer. We sought to describe how this treatment paradigm influenced the use of anthracyclines in this patient setting. We analyzed a multi-institutional database containing the treatment history of 450 patients who received at least one trastuzumab-based regimen for HER-2(+) metastatic breast cancer. Patients were considered eligible for anthracyclines for metastatic disease if they were never exposed (NE) or had been previously exposed (PE) to an anthracycline in the neoadjuvant or adjuvant setting and had relapsed after 12 months from the last dose. We then assessed the use of anthracycline-based therapy after failure with the first trastuzumab-based regimen in eligible patients. Three-hundred twenty-one patients were considered eligible for anthracyclines. In total, 190 eligible patients developing disease progression during the initial trastuzumab-based therapy were analyzed. An anthracycline was administered as first salvage treatment in 14 NE and two PE patients. Another 15 NE and nine PE patients received an anthracycline as a further line of therapy. Of 119 eligible patients who died from breast cancer, only 30 received an anthracycline for metastatic disease. In conclusion, despite the fact that two thirds of the patients receiving trastuzumab-based therapy for HER-2 metastatic breast cancer are eligible for anthracyclines, these drugs are infrequently used nowadays to treat trastuzumab-refractory disease. A role for these compounds should be redefined in this patient subset.
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Antraciclinas/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2 , Estudos Retrospectivos , TrastuzumabRESUMO
The purpose of this article is to evaluate the prognostic value of androgen receptor (AR) expression in patients with estrogen receptor (ER)-positive breast cancer, treated with endocrine therapy, with or without the addition of chemotherapy. A consecutive series of 953 patients with ER-positive breast cancer, treated between 1998 and 2003, was selected. Repeated immunohistochemistry confirmed the expression of ER in the tumor of 938 patients. AR expression was measured by immunohistochemistry. The Kaplan-Meier method, logrank test and multivariate Cox models were used to explore the impact of AR expression on time to relapse (TTR) and disease specific survival (DSS) in all patients and in subgroups treated with chemo-endocrine therapy or endocrine therapy alone. AR immunoreactivity was assessable in 859 tumors and positive in 609 (70.9%). AR expression was a significant marker of good prognosis for TTR (P = 0.001) and DSS (P < 0.001). This effect was particularly evident in the group of patients receiving chemo-endocrine therapy (TTR (P = 0.015) and DSS (P < 0.001)). Cox models confirmed AR as an independent variable for both TTR (P = 0.003, HR 0.444, 95%CI 0.258-0.765) and DSS (P < 0.001, HR 0.135, 95%CI 0.054-0.337). Thus, we focused on ER-positive luminal B breast cancer that may be selected for chemotherapy because of their more aggressive immunophenotype. In this subset AR expression identified a group of patients with better prognosis for TTR (P = 0.017, HR 0.521, 95%CI 0.306-0.888) and DSS (P = 0.001, HR 0.276, 95% CI 0.130-0.588). AR expression is an independent prognostic factor of better outcome in patients with ER-positive breast cancers.
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Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/tratamento farmacológico , Receptores Androgênicos/análise , Receptores de Estrogênio/análise , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/secundário , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Itália , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Combinations of trastuzumab with either docetaxel or vinorelbine are considered valuable treatment options for HER2-positive metastatic breast cancer patients. We performed a retrospective comparison of the clinical outcomes associated with either one of these combinations. METHODS: From a multi-institutional database we retrieved 179 patients treated with either docetaxel or vinorelbine plus trastuzumab as first-line therapy for HER2-positive advanced breast cancer. RESULTS: Docetaxel-trastuzumab was superior to vinorelbine-trastuzumab in terms of response rate (RR: 77 vs 57%, p = 0.01) and median overall survival (OS: 35 vs 23 months, p = 0.04), but not in median time to progression (TTP: 12 vs 10 months, p = 0.53). At multivariate analysis, type of treatment was not associated with TTP but was an independent predictor of OS, with a significant reduction in the risk of death in favor of docetaxel-trastuzumab (HR 0.474, 95% IC 0,303-0.742, p < 0.01). CONCLUSION: Docetaxel or vinorelbine, when combined with trastuzumab, provide excellent rates of tumor control in patients with previously untreated HER2-positive advanced breast cancer. Docetaxel may offer some advantage in terms of response rate and resulted in a significantly prolonged overall survival, which, because of the retrospective design of our study, deserves further investigation in prospective trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Receptor ErbB-2/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxoides/administração & dosagem , Trastuzumab , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
BACKGROUND: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. METHODS: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). RESULTS: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35-82) for the EVA and 57.8 years (range 35.0-82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1-48) and 12.4 months (range 2.9-70.0) in the two data sets, respectively. CONCLUSION: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.
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Sex Hormone-Binding Globulin, the specific carrier for sex steroids, regulates hormone bioavailable fraction and estrogen signaling system in breast cancer cells. A common single nucleotide polymorphism in the human SHBG gene results in an amino acid substitution (Asp327Asn), which introduces an additional N-glycosylation site, and is associated with reduced breast cancer risk in postmenopausal women. The frequency of this polymorphism was evaluated in a group of patients that developed breast cancer while taking hormonal replacement therapy (HRT) for menopause, an interesting model of estrogen exposure. The polymorphism frequency was significantly higher in women taking HRT that didn't develop any breast cancer than in breast cancer patients (P<0.05). To get insight into the underlying mechanisms, we compared the ability of recombinant wild type and variant (D327N) SHBG to influence estradiol effects in MCF-7 breast cancer cells. D327N SHBG was more effective than wild type protein in inhibiting estradiol-induced cell proliferation and anti-apoptosis. This depended on the fact that D327N SHBG binding to MCF-7 cells was significantly higher than that of wild type protein. As a consequence, D327N caused a larger induction of the second messenger cAMP and a deeper inhibition of the estradiol-induced Erk (1/2) phosphorylation. Our observations, demonstrating the increased efficiency of D327N SHBG in counteracting estradiol action and a significantly higher frequency of Asp327Asn polymorphism in women not developing breast cancer after estrogen exposure, first provide evidence for the mechanism of D327N SHBG protective action.
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Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Estrogênios/metabolismo , Polimorfismo de Nucleotídeo Único , Globulina de Ligação a Hormônio Sexual/genética , Globulina de Ligação a Hormônio Sexual/fisiologia , Animais , Apoptose , Neoplasias da Mama/etiologia , Células CHO , Linhagem Celular Tumoral , Cricetinae , Cricetulus , AMP Cíclico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Terapia de Reposição Hormonal , Humanos , Globulina de Ligação a Hormônio Sexual/biossíntese , Transdução de SinaisRESUMO
The prognosis for patients with locally advanced or metastatic breast cancer (mBC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed breast cancer patients present with metastatic disease, and 30%-50% of those diagnosed at earlier stages will subsequently progress to mBC. In terms of ongoing management for advanced/metastatic breast cancer after failure of hormonal therapy, there is a high medical need for new treatment options that prolong the interval to the start of intensive cytotoxic therapy, which is often associated with potentially serious side effects and reduced quality of life. Oral chemotherapeutic agents such as capecitabine and vinorelbine have demonstrated efficacy in patients with mBC, with prolonged disease control and good tolerability. Use of oral chemotherapy reduces the time and cost associated with treatment and is often more acceptable to patients than intravenous drug delivery. Metronomic administration of oral chemotherapy is therefore a promising treatment strategy for some patients with mBC and inhibits tumor progression via multiple mechanisms of action. Ongoing clinical trials are investigating metronomic chemotherapy regimens as a strategy to prolong disease control with favorable tolerability. This article provides an overview of metronomic chemotherapy treatment options in mBC, with perspectives on this therapy from a panel of experts.
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BACKGROUND: Trastuzumab is a monoclonal antibody selectively directed against Her2 and approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include mediation of antibody-dependent cellular cytotoxicity (ADCC) by triggering FcgammaRIII on natural killer (NK) cells. This study addresses the correlation between overall NK function and trastuzumab's clinical activity. SUBJECTS AND METHODS: Clinical and immunological responses were assessed in 26 patients receiving trastuzumab monotherapy as maintenance management after chemotherapy (8 mg/kg load and then standard doses of 6 mg/kg every 3 weeks). Cytotoxic activity against the MHC class I-negative standard NK target K562 cell line and HER2-specific ADCC against a trastuzumab-coated Her2-positive SKBR3 cell line were assessed in peripheral blood mononuclear cells (PBMC) harvested after the first standard dose. After six months, seventeen patients were scored as responders and nine as non-responders according to the RECIST criteria, while Progression-Free Survival (PFS) was calculated during a 12 months follow-up. RESULTS: The responders had significantly higher levels of both NK and ADCC activities (p < 0.05) that were not different from those of eleven normal controls. The NK activity of the non-responders was significantly (p < 0.05) lower than that of the normal controls. At twelve months, there was a marked correlation between PFS and NK activity only. PFS was significantly longer in patients with high levels of NK activity, whereas its pattern was unrelated to high or low ADCC activity. CONCLUSION: One of the mechanisms of action of trastuzumab is NK cell-mediated ADCC lysis of the Her2-positve target cell. We show here that its potency is correlated with the short-term response to treatment, whereas longer protection against tumor expansion seems to be mediated by pure NK activity.
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Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Células Matadoras Naturais/citologia , Anticorpos Monoclonais/química , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-2/química , Células K562 , Leucócitos Mononucleares/metabolismo , Metástase Neoplásica , Receptor ErbB-2/química , Proteínas Recombinantes/química , TrastuzumabRESUMO
BACKGROUND: Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy. PATIENTS AND METHODS: From the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone. RESULTS: We found no difference in response rate (28% vs. 30%; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08). CONCLUSION: Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.
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Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Quinazolinas/uso terapêutico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Lapatinib , Pessoa de Meia-Idade , Estudos Retrospectivos , TrastuzumabRESUMO
BACKGROUND: The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. METHODS: We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR) and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months), time to progression (TTP) and overall survival (OS) from the initiation of vinorelbine-based salvage therapy. RESULTS: In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41%) and 50% (95% C.I. 38%-62%), respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1-63 months). Median TTP and OS were 7.1 months (95% C.I. 6.6-7.7 months) and 21 months (95% C.I. 14.3-27.7 months), respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. CONCLUSION: our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/biossíntese , Terapia de Salvação/métodos , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Estudos Retrospectivos , Trastuzumab , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
To evaluate feasibility, safety, toxicity profile and dosimetric results of volumetric modulated arc therapy (VMAT) to deliver regional nodal irradiation (RNI) after either mastectomy or breast conservation (BCS) in high-risk breast cancer patients. Between January 2015 and January 2017, a total of 45 patients were treated with VMAT to deliver RNI together with whole breast or post-mastectomy radiotherapy. The fractionation schedule comprised 50 Gy in 25 fractions given to supraclavicular and axillary apex nodes and to whole breast (after BCS) or chest wall (after mastectomy). Two opposite 50°-60° width arcs were employed for breast ad chest wall irradiation, while a single VMAT arc was used for nodal treatment. Treatment was generally well tolerated. Acute skin toxicity was G2 in 13.3% of patients. Late skin toxicity consisted of G1 induration/fibrosis in six patients (13.3%) and G2 in 1 (2.2%). Dosimetric results were consistent in terms of both target coverage and normal tissue sparing. In conclusion, VMAT proved to be a feasible, safe and effective strategy to deliver RNI in breast cancer patients after either BCS or mastectomy with promising dosimetric results and a mild toxicity profile.
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Neoplasias da Mama/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Fracionamento da Dose de Radiação , Feminino , Humanos , Linfonodos/patologia , Linfonodos/efeitos da radiação , Mastectomia Segmentar , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Resultado do TratamentoRESUMO
This retrospective multicenter analysis was aimed to evaluate clinical activity and tolerability of eribulin in pretreated metastatic breast cancer patients in clinical practice. Patients treated with eribulin from January 2012 to July 2013 were enrolled in the observational study from 10 italian hospitals. Tumor and toxicity evaluation were performed according to Agenzia Italiana Farmaco. One-hundred and thirteen patients were included in the study. Median age 62 years old. 71.7 % of the patients had visceral involvement and the majority had a burden of disease involving two or more organs with a median number of 2 (1-6). The median number of previous chemotherapy regimens for advanced disease was 3 (1-10). Median number of eribulin cycles was 4 (1-27). Overall response rate was 24 % (95 % CI 16.0-31.8). Clinical benefit rate, was 35.4 % (95 % CI 26.6-44.2). At a median follow-up of 29.6 months (8.3-41.9) the median progression free survival was 3.3 months (0.6-26.7; 95 % CI 2.4-4.2), and the median overall survival 11.6 months (0.6-33.3; 95 % CI 8.7-14.5). No correlation was recorded between subtypes in terms of ORR and CBR. Toxicity was manageable. Main common grade 3-4 toxicities were neutropenia (19.4 %), febrile neutropenia (0.9 %), asthenia (3.5 %), abnormal liver function test (1.8 %), stomatitis (0.9 %). Our results confirm that treatment with eribulin is feasible and safe in real-world patients.
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The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46 Gy/20 fractions or 40.05 Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57 months (range 6-124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6 %, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2 % of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95 %) had good-excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity.
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Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Hipofracionamento da Dose de Radiação , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
We investigated the activity and toxicity of a combination of vinorelbine 25 mg/m2 on days 1 and 15; epirubicin 25 mg/m2 on days 1, 8, 15; and 5-fluorouracil continuous infusion at 200 mg/m2 every day, administered as first-line chemotherapy in anthracycline-naive metastatic breast cancer patients. Fifty-three patients entered the study. Cycles were repeated every 28 days. Objective response was 60% by World Health Organisation (WHO) criteria and 63% by Response Evaluation Criteria in Solid Tumours (RECIST). The median time to progression was 12.7 months (17.6 months in responders) and the median survival duration was 32.9 months. The dose-limiting toxicity was leucopenia (grade 3/4 in 36% of patients). Grade 3/4 non-haematological toxicities included mucositis in 11% of patients, skin and cardiac toxicity in 4% and 2%, respectively. The combination of vinorelbine, epirubicin and 5-fluorouracil continuous infusion was found to be an active and manageable first-line regimen for metastatic breast cancer patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalos de Confiança , Relação Dose-Resposta a Droga , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , VinorelbinaRESUMO
Pituitary metastases occur in 6-8% of breast cancer cases, but are seldom diagnosed and rarely reported. Therefore, it can be challenging to establish a clinical differential diagnosis, and at present, a definitive criteria is not available. The present study discusses the pituitary lesions identified in three patients with breast cancer, and describes their management within the collaborative framework of the Breast Unit at the Città della Salute Hospital, which also included assessment by endocrinologists. The patients were evaluated for anterior and posterior pituitary function, the appearance of the pituitary upon magnetic resonance imaging (MRI), and the oncology status and treatment. In addition, successive analysis of prolactin levels and the MRI was performed. The patients, aged 75, 83 and 76 years old, differed in their clinical presentation and successive evolution. One patient demonstrated an abrupt onset of diabetes insipidus, the second exhibited overt hypopituitarism and the final patient had a pituitary mass discovered by chance. Cases one and three exhibited systemic spread of the breast cancer, with bone and/or parenchymal metastasis, but not brain metastasis. Case two presented with a secondary pituitary tumour alone. In case three, a secondary nature to the pituitary lesion was unlikely, since there was no lesion evolution evident following MRI and as stable prolactin levels were observed over the course of the study period. By contrast, case one presented with a rapid increase of sellar lesions on MRI, together with a progressive rise in prolactin levels. Taking into account the frailty of breast cancer patients who are monitored for disease progression, management in a collaborative framework, such as at the Breast Unit, makes it possible to establish a diagnosis of sellar lesions, which is adequate for the comprehensive management of the patient with successive pituitary MRIs and prolactin evaluations, and avoids unnecessary invasive neurosurgery.
RESUMO
BACKGROUND: To evaluate the feasibility and activity of gemcitabine and vinorelbine as a second/third-line approach in patients with advanced breast cancer. METHODS: Entered into the study were 51 consecutive patients. All had been previously treated with anthracyclines. Of these 51 patients, 36 had experienced failure or relapse after one chemotherapy line for advanced disease, and 15 after two chemotherapy lines. The dominant sites of involvement were brain in 4 patients (7.8%), liver in 22 (43.2%), lung in 10 (19.6%), bone in 10 (19.6), and soft-tissue in 5 (9.8%). Treatment consisted of vinorelbine 25 mg/m(2) and gemcitabine 1000 mg/m(2) administered on days 1 and 8 every 21 days. RESULTS: The scheme was well tolerated. Grade 3/4 neutropenia was observed in 11% of patients. Grade 3 nausea and vomiting occurred in 6%, and grade 2 neurotoxicity in 6%. No patients experienced grade 3/4 alopecia. The median relative dose intensity was 94.6% (49.7-100%) and 90.0% (23.1-100%) for vinorelbine and gemcitabine, respectively. Two patients (3.9%) were not evaluable for disease response, 4 (7.8%) attained a clinical complete response, 13 (25.5%) a partial response (for an overall response rate of 33.3%, 95% coefficient interval 20.0-46.0%), 23 (45.2%) showed stable disease, and 9 (17.6%) progressed. The median time to progression of responding patients was 10.8 months, and the median overall survival of the entire population was 17.8 months. CONCLUSIONS: Vinorelbine and gemcitabine is a manageable scheme with moderate activity in pretreated patients with advanced breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Metástase Neoplásica , Vimblastina/administração & dosagem , Vinorelbina , GencitabinaRESUMO
We conducted a pilot phase II trial of trastuzumab administered concurrently with docetaxel in women with HER2-overexpressing advanced breast cancer. Twenty-five women with HER2-positive (3+ by immunohistochemistry = 16, 2+ = 9) metastatic breast cancer received docetaxel (75 mg/m every 3 weeks for 6 cycles) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). Twenty-three patients (92%) had visceral metastatic involvement. Twenty-three patients had received prior chemotherapy as part of adjuvant (18), metastatic (2), and both (3) treatment. The number of cycles administered was 121 (median 6, range 1-6). Symptomatic cardiotoxicity (GIII) occurred in one patient. The most common grade GIII/IV toxicity was neutropenia (80% of the cycles), although febrile neutropenia did not occur. No other GIII/IV toxicities were observed. Response rate was 70% (1 complete response and 15 partial responses) in 23 evaluable patients. The combination of docetaxel and trastuzumab is well tolerated and has clinically meaningful antitumor activity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Genes erbB-2 , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/patologia , Docetaxel , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Projetos Piloto , TrastuzumabRESUMO
In 2009 a prospective, randomized Phase II trial (NCT00842998) was initiated to evaluate the activity of HER2-targeting agents without chemotherapy (CT) in HER2-positive metastatic breast cancer (MBC) patients. The primary tumors of the patients enrolled in this study offered a unique opportunity to identify biomarkers that could predict durable clinical benefit from CT-free anti-HER2 therapy. Patients with HER2-positive MBC were randomized to trastuzumab or lapatinib as first-line therapy. CT was added to anti-HER2 therapy in patients failing to achieve tumor regression at the 8-week evaluation and in those progressing at any time. Expression analysis of 105 selected genes was performed from formalin-fixed paraffin-embedded primary tumor samples. The research-based PAM50 intrinsic subtypes were also identified. Additionally, quantitative HER2 (H2T) and p95HER2 (p95) protein expression were evaluated by HERmark® and VeraTag® assay, respectively. Predictors of persistence on protocol (PP) were studied by Cox univariate and multivariate analysis. Nineteen patients were enrolled. Median overall survival was 43 months and median PP was 3.8 months (0.8-38.8+), with 4 patients (21.1%) persisting on single agent trastuzumab or lapatinib for longer than 12 mo (14.9-38.8 + mo). Seventeen patients were evaluable for PP. Gene expression analysis revealed that high expression of the 17q12-21 amplicon genes HER2 and GRB7, and the PAM50 HER2-enriched intrinsic profile, were significantly associated with longer PP. Conversely, high expression of luminal-related genes such as PGR, MDM2 or PIK3CA, or the PAM50 luminal intrinsic profile correlated with reduced PP. Moreover, increasing H2T/p95 ratio was found to be significantly associated with longer PP (HR 0.56 per 2-fold increase in H2T/p95, P = 0.0015). Our data suggest that patients belonging to the "HER2-enriched" subtype and/or having high H2T/p95 protein expression ratio are exquisitely sensitive to anti-HER2 agents. MBC patients with these tumors could be candidates for studies aimed at establishing chemotherapy-free regimens.