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BACKGROUND: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2-positive ABC patients with stable or active brain metastases (BMs); however, its efficacy in patients with HER2-low ABC with BMs is not well established yet. METHODS: DEBBRAH is a single-arm, five-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n = 6, asymptomatic untreated BMs) and 4 (n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. RESULTS: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. CONCLUSIONS: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.
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Neoplasias Encefálicas , Neoplasias da Mama , Camptotecina , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Trastuzumab/uso terapêutico , Trastuzumab/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Idoso , Adulto , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologiaRESUMO
BACKGROUND: The Phosphoinositide 3-kinase (PI3K) inhibitors may be used in cancer progression and mortality along with standard therapy to improve therapeutic efficacy of Advanced Breast Cancer (ABC). PURPOSE: This systematic review and meta- analysis were conducted to understand the therapeutic and toxicity profile of PI3K inhibitors in ABC. METHODS: The electronic databases were searched for suitable trials as per the criteria. The outcomes assessed were Progression- Free Survival, Objective Response Rate and Disease Control Rate. The data were systematically reviewed and meta-analyzed by Mantele- Haenszel method. RESULTS: Seven studies were included in the systematic review and meta- analysis. The co- administration of PI3K inhibitors with standard therapy improved the Progression- Free Survival significantly, while a marginal improvement was observed in Objective Response Rate, no difference in Disease Control Rate and toxicity significantly increased. CONCLUSIONS: The addition of PI3K inhibitors decreased the risk of progression but increased the risk of toxicity.
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BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NCH) has demonstrated efficacy in downsizing tumors and facilitating less extensive surgery. However, immediate breast reconstruction (IBR) after NCH has raised concerns regarding higher complication rates. This study evaluates the impact of NCH on outcomes following IBR with a latissimus dorsi flap and implant (LDI) after mastectomy. METHODS: Cases from a prospective maintained database were reviewed, and patients classified according to whether or not they received NCH. Risk factors and major and minor complications in both groups were then analyzed. RESULTS: Among the 196 patients who underwent 198 IBR procedures, 38.4% received NCH and 66.1% did not. The overall complication rate was 46.7% in the non-NCH group and 53.3% in the NCH group (p = 0.650). The presence of comorbidities increased the likelihood of any complication (odds ratio [OR]: 3.46; 95% confidence interval [CI]: 1.38-8.66; p = 0.008) as well as major complications (OR: 3.35; 95% CI: 1.03-10.95; p = 0.045). Although patients in the NCH group experienced more major complications (10.5% vs. 4.9%; p = 0.134) and early loss of breast reconstruction (3.9% vs. 0.8%; p = 0.128), these findings were not statistically significant. CONCLUSION: This study found no statistically significant association between NCH and higher risk of complications or loss of IBR with LDI after mastectomy.
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Neoplasias da Mama , Mamoplastia , Músculos Superficiais do Dorso , Humanos , Feminino , Mastectomia/efeitos adversos , Mastectomia/métodos , Terapia Neoadjuvante/métodos , Resultado do Tratamento , Estudos Prospectivos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/etiologia , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Silicones , Estudos RetrospectivosRESUMO
Background: Recent data suggest that breast-conserving surgery (BCS) may positively impact overall survival (OS) in early breast cancer. However, the role of BCS in locally advanced breast cancer (LABC) following neoadjuvant therapy (NAT) remains uncertain. Methods: We conducted a retrospective cohort study involving 530 LABC patients who underwent surgery after NAT between 2010 and 2015. Outcomes examined included OS, distant recurrence rates (DRR), and loco-regional recurrence rates (LRRs). Results: Among the 927 breast cancer patients who received NAT, 530 were eligible for our study. Of these, 24.6% underwent BCS, while 75.4% underwent mastectomy (MS). The median follow-up duration was 79 months. BCS patients exhibited a higher pathological complete response (PCR) rate compared to those who underwent MS (22.3% vs. 10%, p < 0.001). The 6-year OS rates for BCS and MS were 81.5% and 62%, respectively (p < 0.000). In multivariate OS analysis, MS was associated with worse outcomes (OR 1.678; 95% CI 1.069-2.635; p = 0.024), as was body mass index (BMI) (OR 1.031; 95% CI 1.006-1.058; p = 0.017), and stage IIIB or IIIC (OR 2.450; 95% CI 1.561-3.846; p < 0.000). Conversely, PCR (OR 0.42; 95% CI 0.220-0.801; p = 0.008) was associated with improved survival. DRR was significantly lower in BCS (15.4%) compared to MS (36.8%) (OR 0.298; 95% CI 0.177-0.504). LRRs were comparable between BCS (9.2%) and MS (9.5%) (OR 0.693; 95% CI 0.347-1.383). Conclusion: Our findings suggest that BCS is oncologically safe, even for patients with large lesions, and is associated with superior OS rates compared to MS. Additionally, lower BMI, lower pretreatment stage, and achieving PCR were associated with improved survival outcomes.
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Advanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer.
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Neoplasias da Mama , Médicos , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , GenômicaRESUMO
Background: Breast cancer is the most frequent malignant tumor in women. Objective: To identify clinico-pathological and molecular markers as predictors of survival in patients with locally advanced breast cancer (LABC). Methods: Retrospective and observational study. The clinical factors of clinico-pathological and molecular predictors in relation with overall survival (OS) were assessed by the survival function, baseline hazard with smoothing and Cox regression. Results: 126 patients were assessed. OS at five years was significantly superior in patients with clinical stage IIIA (87%; p < 0.001), grade 2 tumor (81%; p < 0.001), pathological node stage (ypN0: 90%; p < .001), low-risk Nottingham prognostic index (86%; p < 0.001) and luminal A subtype (88%; p = 0.022). Baseline hazard with smoothing exhibited an increase in the mortality rate at 50 months for the luminal B/ HER2+ subtype compared with other subtypes. The multivariate analysis ascertained that the stage ypN2-3 (hazard ratio [HR] = 7.3; 95% confidence interval [95% CI]: 2.2 to 23.9) and the HER2+ nonluminal (HR = 7.8; 95% CI: 2 to 29.6) and triple negative (HR = 5.4; 95% CI: 1.7 to 17.2) subtypes were associated with a poor OS. Conclusions: The comprehensive evaluation of the molecular marker and clinico-pathological factors provides more accurate predictive and prognostic information. The nodal stage and molecular subtype are suitable clinical parameters on survival for LABC patients.
Introducción: el cáncer de mama es el tumor maligno más frecuente en las mujeres. Objetivo: identificar marcadores clínico-patológicos y moleculares como predictores de la supervivencia en pacientes con cáncer de mama localmente avanzado (CMLA). Material y métodos: estudio retrospectivo y observacional. Los factores clínico-patológicos y moleculares fueron evaluados en relación con la supervivencia global (SG) mediante la función de supervivencia, riesgo basal con suavizamiento y regresión de Cox. Resultados: 126 pacientes fueron evaluadas. La SG a cinco años fue significativamente superior en pacientes con estadio clínico IIIA (87%; p < 0.001), tumor de grado 2 (81%; p < 0.001), ausencia de ganglios patológicos (ypN0: 90%; p < 0.001) y en el subtipo luminal A (88%; p = 0.022). El riesgo basal con suavizamiento exhibió un incremento en la tasa de mortalidad a los 50 meses para el subtipo luminal B/ HER2+ comparado con los otros subtipos. En el análisis multivariado, el estadio ypN2-3 (razón de riesgo [RR] = 7.3; intervalo de confianza del 95% [IC 95%]: 2.2 a 23.9) y los subtipos HER2+ (RR = 7.8; IC 95%: 2 a 29.6) y triple negativo (RR= 5.4; IC 95%: 1.7 a 17.2) se asociaron con una pobre SG. Conclusiones: la evaluación integral del marcador molecular y de los factores clínico-patológicos proporciona información predictiva y pronóstica más precisa. El estadio ganglionar y subtipo molecular son parámetros adecuados con un impacto pronóstico en la SG para las pacientes con CMLA.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Prognóstico , Estudos Retrospectivos , Receptor ErbB-2 , Modelos de Riscos Proporcionais , Biomarcadores TumoraisRESUMO
Background: The addition of cyclin-dependent kinases inhibitors (CDKi) to endocrine therapy (ET) as the first- or second line treatment improves progression-free and overall survival (OS) in hormone receptor-positive, HER2 negative (HR+/HER2-) advanced stage breast cancer (ABC). Our study compared survival rates and prognostic factors in Chilean patients that used palbociclib as first or subsequent (≥second) lines of treatment in a real-world setting. Methods: Our retrospective population-cohort study included HR+/HER2- ABC patients. We calculated 5-year OS and performed a multivariate analysis to determine prognostic factors. Results: A total of 106 patients were included. Median age was 49 years (19-86), 28.3% (30) had de novo stage IV disease; 63% received palbociclib with ET as first line, 54% of them with aromatase inhibitor over fulvestrant. Median OS for the entire cohort was 99 months and 5-year OS was 69%. Patients that received first line palbociclib had a 5-year OS of 89% versus 43% for ET monotherapy or ≥second line palbociclib (p = 0.0062). Multivariate analysis showed that the year at diagnosis and CDKi timing (first line versus ≥second line) were significantly associated with OS. Conclusion: Our real-world data show that first-line CDKi + ET provides a statistically significant benefit in OS versus ≥second line in HR+/HER2- ABC patients.
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OBJECTIVES: Several trials have demonstrated the benefit of the CDK 4/6 inhibitors for postmenopausal women with luminal advanced breast cancer. This research aims to compare the cost-utility of the CDK 4/6 inhibitors in patients with no history of resistance to endocrine therapy. METHODS: A Markov model was constructed to estimate the incremental cost per quality-adjusted life-years (QALYs) of treatments from the Brazilian public health system perspective over a lifetime horizon (30 years) with 5% annual discount rate for both benefits and costs. Efficacy parameters were extracted from the pivotal studies. Costs were based on open data from the Brazilian Ministry of Health. The utilities were calculated according to the overall population preferences from a British study. Deterministic and probabilistic sensitivity analyses evaluated the robustness of the results. RESULTS: The most cost-effective drug was ribociclib (US$50 748/QALY), followed by abemaciclib (US$64 052/QALY) and palbociclib (US$65 289/QALY). The univariate analysis showed that the incremental cost-utility ratio (ICUR) was mainly sensitive to the overall survival hazard ratio. The one thousand-probabilistic simulation showed that all ICUR values were above classical thresholds such as 1 to 3 gross domestic product (GDP) per capita per QALY. CONCLUSIONS: Even though there is no established willingness to pay threshold in Brazil, the estimated ICUR for CDK 4/6 inhibitors is >6 times the Brazilian GDP per capita (GDP per capita = US$5694.73), which might be a barrier to their inclusion in the Brazilian public health system.
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Neoplasias da Mama , Brasil , Neoplasias da Mama/tratamento farmacológico , Análise Custo-Benefício , Feminino , Humanos , Modelos Econômicos , Pós-MenopausaRESUMO
Introduction: The objective of this study is to describe the profile of patients from a public institution, submitted to neoadjuvant chemotherapy (NACT), comparing the verified pathological response with literature data. Methods: Observational retrospective cohort study on breast cancer patients diagnosed between September 2001 and October 2018 and treated with NACT at Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ), located in Rio de Janeiro, Brazil. The adopted neoadjuvant chemotherapy regimen was based on anthracycline and docetaxel. Results: A total of 133 patients were evaluated. The average age in this group was 54 years (28-86), 49 women (37%) were under 50 years old. The following distribution by molecular subtype was observed: overexpression or amplification of the human epidermal growth factor receptor 2 (HER2+) (13 women, 26.6%), Luminal (19 women, 38.8%), and Triple-negative (TN) (17 women, 34.6%). The HER2+ and TN subtypes had a higher incidence of cases between 40-49 years and 50-59 years. As for the initial staging, 34% were IIIA; 26%, IIB; and 19%, IIIB. Only one patient did not undergo surgery after NACT, 33 (24.8%) underwent conservative surgery, and 99 patients (74.4%) underwent mastectomy. Regarding the axillary approach, 41 (31%) underwent sentinel lymph node biopsy and 88 (66%) had an indication for lymphadenectomy. In the anatomopathological evaluation of the surgery, 12 (9.1%) patients obtained a pathologic complete response (pCR) and 113 (84.9%), partial or no response to chemotherapy. Conclusion: This research enabled the identification of clinicopathologic characteristics and outcome of patients who received neoadjuvant chemotherapy in a public university service. The predominance of advanced tumors was observed, stressing the need for public health policies for the screening of breast cancer as well as the guarantee of timely treatment for diagnosed cases. The data somewhat reflect the difficulty that the public sector encounters to carry out the most appropriate treatment. The authors expect that this article, by analyzing the profile and the adopted treatment in real-life cases and in a public university institution, can contribute to the improvement of breast cancer treatment in Brazil.
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HER2-positive breast cancer is an aggressive subtype identified in the 1980s. The development of therapies targeting the HER2 has improved outcomes. The current standard of care, established in 2012 is dual blockade with trastuzumab + pertuzumab as first-line followed by TDM-1 as second-line. Several suboptimal choices are available in third-line or more. In 2019 the presentation of several trials evaluating new drugs and regimens in third-line has re-opened questions about sequencing, treatment of triple positive disease and treatment choice after exposure to TDM-1. These include tucatinib, neratinib and trastuzumab-deruxtecan. Other agents - including other antibody drug conjugates and bispecific antibodies as well as combinations - will lead to further changes in coming years. Additionally, should the numerous putative biomarkers thus identified ever come into use at the clinic, choice of treatment and response evaluation may be substantially changed.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: In hormone receptor-positive, HER-2 negative (HR+/HER2-) advanced breast cancer (ABC) endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in first and second line improved progression-free survival (PFS), overall response rate (ORR) and clinical benefit rate (CB) without deterioration in quality of life compared with ET alone. In addition, recent data showed improvement in overall survival (OS) for premenopausal women in first line setting and for different subgroups of patients in second line. Since 2015, in Argentina, the combination of ET with CDK4/6i is a standard of care in HR+/HER2- ABC. METHODS: We carried out a prospective analysis of real-world use of palbociclib with ET in HR+/HER2- ABC patients who received treatment between October 2015 and August 2019 in two private institutes from Buenos Aires, Argentina. The aims of the study were to determine efficacy and safety of patients treated with ET and palbociclib, describe patient profile and treatment strategy beyond progression. RESULTS: One-hundred and twenty-eight patients were included in the final analysis. Main baseline characteristics include, median age 57 years, 20% were premenopausal women, 44% had visceral metastasis and 26% bone only disease. More than half of patients had two or more metastatic sites, 44.4% had performance status 1, and most of them (59.4%) were treated with palbociclib in first-line setting. Palbociclib was preferentially associated with aromatase inhibitors in 63.9% of patients, and with fulvestrant in the remaining. All premenopausal women received ovarian suppression or ovarian ablation (OS/OA). The median PFS was 36.7 months in first line and 24.2 months in second line. The ORR was 45.3% and 25.0% in first and second line, respectively. The median OS in the entire population was not reached. Half of patients did not require dose interruption and/or delay, dose reduction was required in 15% of patients and almost no patients required drug discontinuation (2.0%). With regard to safety, 55% of patients developed grade 3-4 adverse events, 20% neutropenia grade 3-4, and 7% febrile neutropenia. Infections were presented in one out of three patients, mostly uncomplicated. CONCLUSIONS: This is the first prospective evidence of real-world use of palbociclib in a Latin American population. We found similar outcomes to the PALOMA-2 and PALOMA-3 randomised trials and Real-World Data already published, with lower incidence of side effects and treatment discontinuation, but with higher incidence of febrile neutropenia.
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Breast cancer (BC) is the most common malignancy in women. We retrieved medical records from >2,000 Chilean BC patients over the 1997-2018 period. The objective was to assess changes in clinical presentation or prognosis of our patients throughout these 20 years of practice. Although most variables did not display significant variations, we observed a progressive increase in stage IV BC over this period. Our data showed that tumour stage III/IV or HER2-enriched subtype tumours were associated with poorer prognosis. In contrast, we found that patients diagnosed by mammography had better overall survival. We speculate that better screenings and more sensitive imaging could explain the unexpected rise in stage IV cases. Our results support mammography screenings as an effective measure to reduce BC-related mortality.
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BACKGROUND: The management of small skin-involved (SI) invasive breast cancers is controversial because although they are considered unresectable, their prognosis is far better than their stage III classification. This study was undertaken to determine how SI lesions are treated in the United States and to discern the benefit of systemic therapy. PATIENTS AND METHODS: Data of patients diagnosed with stage I-III breast cancer in the National Cancer Data Base between 2004 and 2011 were reviewed. Treatment patterns were examined and overall survival assessed. RESULTS: A total of 3485 patients had SI and 456,287 patients had non-SI breast cancers. Chemotherapy was administered to 68.5% of SI and 45.9% of non-SI tumors (P < .001), including 77.2% of SI and 33% of non-SI tumors < 2 cm (P < .001). After adjusting for patient and tumor characteristics, SI patients were 19.4% more likely to receive chemotherapy than non-SI patients. Radiotherapy was provided to 61.1% of SI and 64.3% of non-SI tumors (P < .001), including 65.5% of SI and 66.5% non-SI tumors < 2 cm (P = .711). After adjusting for patient and tumor characteristics, SI patients were 76.6% more likely to receive radiotherapy than non-SI patients. Chemotherapy and radiotherapy provided an overall survival benefit for stage II and III SI and non-SI tumors. CONCLUSION: Despite controversy regarding staging and prognosis of SI tumors, the majority of patients are provided systemic therapy and radiotherapy. Varied patterns of chemotherapy administration for SI tumors suggests that further treatment guidance and standardization are required, especially because chemotherapy and radiotherapy are equally efficacious in SI and non-SI tumors alike.
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Neoplasias da Mama/terapia , Quimiorradioterapia/mortalidade , Terapia Neoadjuvante/mortalidade , Aceitação pelo Paciente de Cuidados de Saúde , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias Cutâneas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
Breast cancer (BC) is a highly prevalent malignancy in Latin American women, most cases being diagnosed at locally advanced or metastatic stages when options for cancer care are limited. Despite its label as a public health problem in the region, Latin American BC patients face several barriers in accessing standard of care treatment when compared with patients from developed countries. In this review, we analyse the landscape of the four main identified barriers in the region: i) high burden of locally advanced/advanced BC; ii) inadequate access to medical resources; iii) deficient access to specialised cancer care and iv) insufficient BC research in Latin America. Unfortunately, these barriers represent the main factors associated with the BC poor outcomes seen in the region. Targeted actions should be conducted independently by each country and as a region to overcome these limitations and create an enhanced model of BC care.
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OBJECTIVE: To assess the pathological complete response (pCR) rate after neoadjuvant chemotherapy (NC) with anthracyclines with or without taxanes in management of locally advanced breast cancer (LABC). METHOD: Patients with LABC were included. A cohort received four cycles of 5-fluorouracil [FEC] (FEC 500 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2) every 3 weeks followed by four cycles of docetaxel (D) 75 mg/m2 as 1 h infusion intravenous every 3 weeks. Another cohort received six cycles of FE100C (500, 100 and 600 mg/m2). The chemotherapy was followed by surgery and radiotherapy. RESULTS: There was no statistically significant difference in overall response rate (ORR) (ORR: 78.5 vs. 85%; p = 0.299) and clinical complete response (cCR) (c CR: 20.6 vs. 33.3%; p = 0.103) for 4FECâ4D compared to 6FE100C, respectively. Instead, there was a statistically significant improved rate of pCR (30.2 vs. 16.7%; p = 0.049) and negative axillary lymph nodes (51.6 vs. 35%; p = 0.03) for 4FECâ4D compared to 6FE100C, respectively. Serious toxicity was low and non-significant in both cohorts. The logistic regression multivariate models showed that main significant predictors to obtain a pCR were 4FECâ4D NC (odds ratio [OR]: 2.7; p = 0.019) and stage IIIA (OR: 3.8; p = 0.002). CONCLUSION: This study showed that 4FECâ4D regimen with conventional dose is highly active and well tolerated in patients with LABC in our hospital.
OBJETIVO: Evaluar la tasa de respuesta patológica completa (RPc) posterior a la quimioterapia neoadyuvante (QN) con antraciclinas con o sin taxanos en el manejo del cáncer de mama localmente avanzado (CMLA). MÉTODO: Se incluyeron pacientes con CMLA. Una cohorte recibió cuatro ciclos de FEC (5-fluorouracilo 500 mg/m2, epirubicina 75 mg/m2, ciclofosfamida 500 mg/m2) cada 3 semanas seguido por cuatro ciclos de docetaxel (D) 75 mg/m2 en infusión intravenosa de 1 hora cada 3 semanas. Otra cohorte recibió seis ciclos de FE100C (500, 100 y 600 mg/m2). Se realizó cirugía posterior a la quimioterapia. RESULTADOS: No hubo diferencia estadísticamente significativa en las tasas de respuesta objetiva (78.5 vs. 85.0%; p = 0.299) ni en la respuesta clínica completa (20.6 vs. 33.3%; p = 0.103) para 4FECâ4D comparado con 6FE100C, respectivamente. En cambio, hubo una mejora significativa en la tasa de RPc (30.2 vs. 16.7%; p = 0.049) y en los ganglios linfáticos axilares negativos (51.6 vs. 35%; p = 0.03) para 4FECâ4D en comparación con 6FE100C, respectivamente. La toxicidad grave fue baja y no significativa en ambas cohortes. Los modelos multivariados de regresión logística mostraron que los principales predictores significativos para obtener una RPc fueron la QN con 4FECâ4D (odds ratio [OR]: 2.7; p = 0.019) y el estadio IIIA (OR: 3.8; p = 0.002). CONCLUSIÓN: Este estudio mostró que el régimen 4FECâ4D con dosis convencional es muy activo y bien tolerado en pacientes con CMLA en nuestro hospital.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Docetaxel/administração & dosagem , Epirubicina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Estudos de Coortes , Docetaxel/efeitos adversos , Quimioterapia Combinada , Epirubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The estrogen receptor (ER) has been targeted for breast cancer treatment for over a century, but many challenges persist. ER-positivity identifies the largest breast cancer subgroup, and ER-directed therapies prolong survival and improve symptoms in the advanced setting with a very favorable side effect profile. Treatment strategies have included decreasing estrogen synthesis and modulating or degrading the ER. However, ER+ breast cancer once diagnosed in the advanced setting still represents an incurable condition. Many efforts are ongoing to circumvent resistance mechanisms with a few strategies already incorporated into clinical practice such as the combination of endocrine agents with drugs that interfere with other signaling pathways and cell-cycle progression. Important questions remain as how best to select each available strategy, how to sequence them and ultimately how to extend benefits to the largest number of patients in need.
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Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Neoplásica , Receptor ErbB-2/genética , Receptores de Estrogênio/genéticaRESUMO
The purpose of this study was to investigate some possible mechanisms underlying the in vitro antitumor activity of tea tree oil (TTO) on human and mouse breast cancer cells (MCF-7 and 4T1, respectively) and its cytotoxicity on fibroblasts (HFF-1) and on peripheral blood mononuclear cells (PBMCs). TTO High-Resolution Gas Chromatography (HRGC) showed seventeen main constituents, such as Terpinen-4-ol, γ-Terpinene, and α-Terpinene. High TTO concentrations (≥ 600⯵g/mL) showed a remarkable antitumor activity, decreasing cell viability and cell proliferation of MCF-7 and 4T1 cells. TTO at 300⯵g/mL increased the number of MCF-7 cells in the early stages of apoptosis and increased the BAX/BCL-2 genes ratio. TTO, mainly at 300⯵g/mL, decreased cell growth and arrested MCF-7 cells in the S phase of the cell cycle. Lower antitumor concentrations (≤300⯵g/mL) evaluated in MCF-7 and 4T1 cells were not cytotoxic to PBMCs and HFF-1. Also, TTO (300⯵g/mL) was able to induce cell proliferation in fibroblasts after 72â¯h, indicating non-cytotoxic effect in these cells. TTO exhibited in vitro antitumor effect on MCF-7 and 4T1 cells by decreasing cell viability and modulating apoptotic pathways and cell cycle arrestment of MCF-7 cells. In this sense, our study provides new perspectives on the potential use of TTO for the development of new alternative therapies to treat topically locally advanced breast cancer (LABC).
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Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Fibroblastos/citologia , Leucócitos Mononucleares/citologia , Óleo de Melaleuca/farmacologia , Adulto , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Modelos Biológicos , Adulto JovemRESUMO
BACKGROUND: Over the last 20 years, aromatase inhibitors (AI) have been tested in clinical trials as first-line therapy for hormone receptor-positive (HR-positive) advanced breast cancer (ABC), firstly as experimental arms, when they proved to be effective, and recently as control arms. This analysis aims to evaluate trends in progression-free survival (PFS) and time to progression (TTP) over time. PATIENTS AND METHODS: A literature review was conducted using the MEDLINE database to identify randomized controlled phase II or III trials which reported PFS or TTP of at least one arm using first-line AI HR-positive ABC patients. A linear correlation was used to access the association between the year of the first patient enrolled and the observed PFS/TTP. RESULTS: The search retrieved 19 trials, accounting for 4552 postmenopausal patients divided into 21 separate AI treatment arms. The PFS/TTP increased from 6 to 9 months in the earlier trials to 13-16 months in the current era, representing an absolute gain of approximately 7 months, without the addition of any other drug. Our analysis showed a positive correlation between the year of the first patient enrolled in these trials and median PFS/TTP reported (R 2 = 0.34; p < 0.01). No correlation was found between the year of the first patient included in these trials and other potential prognostic factors such as visceral metastasis at baseline (R 2 = 0.26; p = 0.20) or exposure to adjuvant therapy (R 2 = 0.05; p = 0.18). CONCLUSION: Patients treated with first-line AIs in the more recently conducted trials have longer PFS/TTP when compared to their counterparts treated with the same drugs in older studies. These findings have important implications for the estimation of sample size and follow-up periods for the planning of future trials as well as in the translation of the results into clinical practice decisions.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Progressão , Neoplasias da Mama/patologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Feminino , Humanos , Mortalidade/tendências , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores de TempoRESUMO
INTRODUCTION: This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data. MATERIALS AND METHODS: Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile. RESULTS: A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%). CONCLUSIONS: Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.