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2.
Breast J ; 26(4): 630-642, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31709685

RESUMO

Endocrine therapy (ET) has been regarded for many years as the standard treatment for patients with hormone receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer (ABC) without visceral crisis. However, the efficacy of single-agent ET is constrained by the development of resistance, attributed to alterations in several intracellular signaling pathways, including those related to cell cycle dysregulation. The cyclin-dependent kinases 4 and 6 (CDK4/6) are principal regulators of cell cycle progression from the G1-phase into the DNA synthesis (S)-phase. In vitro inhibition of CDK4/6 activity has potent antiproliferative properties against luminal breast cancer cell lines, which are enhanced when combined with traditional ET. This has led to a substantial interest in targeting this pathway to overcome endocrine resistance in the clinic. Three selective CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) have been approved as first-line therapy in combination with an aromatase inhibitor, or fulvestrant in the case of ribociclib in patients with ER+/HER2- ABC. To date, there is no clue as to which subgroup of patients might benefit most from these combinations. Here, we outline some of the established approaches to overcome endocrine resistance, with special emphasis on the unique mechanism of action of CDK4/6 inhibitors.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina , Feminino , Humanos , Terapia de Alvo Molecular , Pós-Menopausa , Inibidores de Proteínas Quinases/uso terapêutico
3.
Breast Cancer Res Treat ; 160(1): 145-152, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27628191

RESUMO

PURPOSE: To evaluate breast cancer-specific survival at 10 years in patients who present with primary stage IV breast cancer, and to determine whether survival varies with age of diagnosis. METHODS: We retrieved the records of 25,323 women diagnosed with primary stage IV breast cancer in the surveillance, epidemiology, and end results 18 registries database from 1990 to 2012. For each case, we extracted information on age at diagnosis, tumour size, nodal status, oestrogen receptor status, progesterone receptor status, ethnicity, cause of death and date of death. The Cox proportional hazards model was used to estimate the unadjusted and adjusted hazard ratio (HR) of death due to stage IV breast cancer, according to age group. RESULTS: Among 25,323 women with stage IV breast cancer, 2542 (10.0 %) were diagnosed at age 40 or below, 5562 (22.0 %) were diagnosed between ages 41 and 50 and 17,219 (68.0 %) were diagnosed between ages 51 and 70. After a mean follow-up of 2.2 years, 16,387 (64.7 %) women died of breast cancer (median survival 2.3 years). The ten-year actuarial breast cancer-specific survival rate was 15.7 % for women ages 40 and below, 14.9 % for women ages 41-50 and 11.7 % for women ages 51 to 70 (p < 0.0001). In an adjusted analysis, the risk of death from breast cancer at 10 years was significantly lower for women ages 40 and below (HR 0.78; 95 % CI 0.74-0.82; p < 0.0001) and for women ages 41-50 (HR 0.82; 95 % CI 0.79-0.85; p < 0.0001), compared to women ages 51-70. CONCLUSIONS: Approximately 13 % of women with primary stage IV breast cancer survive 10 years after diagnosis. Women diagnosed with stage IV breast cancer before age 50 have better survival at 10 years compared to older women.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , Estados Unidos/epidemiologia
4.
Breast Cancer Res ; 17: 2, 2015 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-25572591

RESUMO

INTRODUCTION: Circulating tumor cells (CTCs) are an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer. Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. The prognostic value of a CTC count in newly diagnosed IBC has not been established. The aim of this study was to assess the prognostic value of a baseline CTC count in patients with newly diagnosed IBC. METHODS: This retrospective study included 147 patients with newly diagnosed IBC (77 with locally advanced and 70 with metastatic IBC) treated with neoadjuvant therapy or first-line chemotherapy during the period from January 2004 through December 2012 at The University of Texas MD Anderson Cancer Center. CTCs were detected and enumerated by using the CellSearch system before patients were started with chemotherapy. RESULTS: The proportion of patients with ≥1 CTC was lower among patients with stage III than among patients with metastatic IBC (54.5% versus 84.3%; P=0.0002); the proportion of patients with ≥5 CTCs was also lower for stage III than for metastatic IBC (19.5% versus 47.1%; P=0.0004). Patients with fewer than five CTCs had significantly better progression-free survival (PFS) (hazard ratio (HR)=0.60; P=0.02) and overall survival (HR=0.59; P=0.03) than patients with five or more CTCs. Among patients with stage III IBC, there was a nonsignificant difference in PFS (HR=0.66; 95% confidence interval (CI), 0.31 to 1.39; P=0.29) and OS (HR=0.54; 95% CI, 0.24 to 1.26; P=0.48) in patients with no CTCs compared with patients with one or more CTCs. In multivariate analysis, CTC was prognostic for PFS and OS independent of clinical stage. CONCLUSIONS: CTCs can be detected in a large proportion of patients with newly diagnosed IBC and are a strong predictor of worse prognosis in patients with newly diagnosed IBC.


Assuntos
Neoplasias Inflamatórias Mamárias/diagnóstico , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Neoplasias Inflamatórias Mamárias/mortalidade , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
5.
Oncology ; 89(2): 79-87, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25832113

RESUMO

BACKGROUND: Studies have shown a moderate increase in survival over time among patients with stage IV breast cancer. Median survival is approximately 2 years. The aim of this study was to evaluate trends over time in survival of >2 years of patients with synchronous stage IV disease. METHODS: Using the SEER (Surveillance, Epidemiology and End Results) registry, we identified patients with synchronous stage IV breast cancer diagnosed between 1990 and 2007. Patients were divided into 3 groups according to the year of diagnosis (1990-1995, 1996-2000, and 2001-2007). The probability of survival of >2 years was computed within each group of diagnosis years. A multivariate logistic regression model was then fit to determine the association between year of diagnosis and probability of surviving >2 years after adjusting for important prognostic factors. RESULTS: 22,601 patients were identified, of whom 9,435 (41.7%) had an overall survival of >2 years. The probability of breast cancer-specific survival (BCSS) of >2 years was 40.1, 44, and 48.1% among patients diagnosed in the periods 1990-1995, 1996-2000, and 2001-2007, respectively (p < 0.001). In the multivariate model, the probability of BCSS of >2 years increased with the more recent year of diagnosis (OR 1.058, 95% CI 1.046-1.069, p < 0.001). Other factors significantly associated with an increased probability of surviving >2 years included surgery of the primary tumor, lower grade, younger age, hormone receptor-positive disease, and noninflammatory disease. CONCLUSION: Our results indicate that among the patients with synchronous stage IV breast cancer, the probability of BCSS of >2 years in the US has increased over time. Attributable factors may be the increasing number of efficacious agents and improved palliative care services over time.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Resultado do Tratamento
6.
Future Oncol ; 11(6): 923-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25760974

RESUMO

Pertuzumab is a humanized monoclonal antibody targeting HER2 that is different from trastuzumab in that it binds to a different domain of HER2; hence, combining the two drugs leads to a more comprehensive blockade of the receptor. This is the first drug to receive fast-track approval from US FDA based on the pathologic complete response (as the primary end point) attained in patients treated with neoadjuvant chemotherapy for breast cancer. Pertuzumab is approved in first-line treatment in metastatic setting both by FDA and EMA in combination with trastuzumab and docetaxel. Combining two targeted therapies ('dual blockade') will certainly escalate treatment costs and it remains to be seen if this strategy will find its way in to the clinic for all patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Feminino , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Resultado do Tratamento
7.
Future Oncol ; 11(10): 1463-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25963424

RESUMO

Buparlisib (formerly BKM 120), an oral 2,6-dimorpholino pyrimidine derivative is a potent pan-PI3K inhibitor causing inhibition of PI3K downstream signaling including downregulation of p-Akt and p-S6R and apoptosis of cancer cells. Buparlisib is rapidly absorbed, has more than 90% bioavailability, good blood-brain barrier penetration and half-life of 40 h. Phase I trials have shown good disease control rate with tolerable toxicity profile at the recommended doses of 100 mg. The most common adverse events noted with buparlisib are rash, hyperglycemia, derangement of liver functions and psychiatric events. Several clinical trials with buparlisib alone or in combination with chemotherapy and targeted therapies are underway. Buparlisib has not yet been approved for regular use. Further randomized trials are required before buparlisib is approved for treatment of breast cancer.


Assuntos
Aminopiridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Morfolinas/uso terapêutico , Aminopiridinas/química , Aminopiridinas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Morfolinas/química , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento
8.
Future Oncol ; 11(8): 1191-200, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25832876

RESUMO

BACKGROUND: Gemcitabine-platinum (Gem-P) is the current standard for patients with advanced gall bladder cancer. MATERIALS & METHODS: This is retrospective analysis of a prospectively maintained database of 210 patients with advanced gall bladder cancer treated with Gem-P between January 2012 and September 2013. RESULTS: Median age was 53 years, 65.2% females. In total,158 patients had metastatic and 52 had locoregional disease. Median number of cycles was 5 (1-12). At a median follow-up of 10 months, median overall survival/progression-free survival was 10/5 months, respectively. On multivariate analysis, patients who underwent prior surgery for primary and locoregional disease had a significantly better progression-free survival and those with locoregional disease had a significantly better overall survival. A total of 45.7% received second-line chemotherapy. CONCLUSION: Use of Gem-P in Indian patients leads to slightly worse outcomes suggesting an aggressive biology.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/patologia , Cuidados Paliativos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Índia , Mosquiteiros Tratados com Inseticida , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Gencitabina
9.
Oncology (Williston Park) ; 28(12): 1101-7, 1110, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25510809

RESUMO

The survival of patients with cancer has improved significantly, primarily because of multidisciplinary care, improved chemotherapeutic agents in both the adjuvant and metastatic settings, the introduction of targeted biologic agents, and the incorporation of palliative care services into the management scheme. However, despite these advances, a significant proportion of patients continue to experience recurrence after adjuvant treatment, and survival associated with stage IV solid tumors still remains low. A primary or acquired resistance to chemotherapeutic and biologic agents is responsible for the failure of many of the agents used to treat patients with a malignancy. This can be explained by the presence of intratumoral heterogeneity and the molecular complexity of many cancers. Factors contributing to intratumoral heterogeneity include genetic mutations, interactions with the microenvironment-and the presence of cancer stem cells. Cancer stem cells have been identified in a number of solid tumors, including breast cancer, brain tumors, lung cancer, colon cancer, and melanoma. Cancer stem cells have the capacity to self-renew, to give rise to progeny that are different from them, and to utilize common signaling pathways. Cancer stem cells may be the source of all the tumor cells present in a malignant tumor, the reason for the resistance to the chemotherapeutic agent used to treat the malignant tumor, and the source of cells that give rise to distant metastases. This review will focus on properties of cancer stem cells; will compare and contrast the cancer stem cell model with the clonal evolution model of tumorigenesis; will discuss the role of cancer stem cells in the development of resistance to chemotherapy; and will review the therapeutic implications and challenges of targeting cancer stem cells, with an assessment of the potential such an approach holds for improving outcomes for patients with cancer.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/patologia , Animais , Humanos , Terapia de Alvo Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo
10.
Front Oncol ; 14: 1374087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800398

RESUMO

Background: Comprehensive molecular profiling of tissue samples that can help guide therapy management is not widely available across the globe. Methods: Comprehensive molecular profiling through Caris Molecular Intelligence involves the analysis of DNA through next-generation sequencing, chromogenic or fluorescent in situ hybridization, pyrosequencing, and copy number alterations; RNA through whole-transcriptome sequencing and multiplex PCR of RNA; and protein through immunohistochemistry. Results: Here we describe the experience of molecular profiling of tumor tissue samples from patients diagnosed with advanced solid tumors and treated in two countries, the United Arab Emirates and Thailand. Tumor cancer cases submitted to Caris Life Sciences (Phoenix, Arizona, USA) for molecular profiling from the UAE and Thailand were retrospectively analyzed (data accessed between 2019 and 2020) for their molecular alterations and clinical biomarkers, without regard to ethnicity. A total of 451 samples from 35 distinct types of advanced cancers were examined for mutations, amplifications, overexpression, exon copy number alterations, microsatellite instability, deficient mismatch repair, tumor mutational burden, and fusions. Interrogating each step of the biological pathway, from DNA to RNA to distinct protein, identified an alteration with an associated therapy for 75% of these tumor samples. The most common alterations identified included elevated PDL-1 that can be targeted with an immune checkpoint inhibitors and amplification of HER2 for which a variety of anti HER2 therapies are available. Conclusion: Comprehensive molecular profiling in patients with advanced malignancies can help optimize therapeutic management allowing for improved prognostic outcome.

11.
JCO Glob Oncol ; 10: e2300330, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484196

RESUMO

PURPOSE: Accurate understanding of the genomic and transcriptomic data provided by next-generation sequencing (NGS) is essential for the effective utilization of precision oncology. Molecular tumor boards (MTBs) aim to translate the complex data in NGS reports into effective clinical interventions. Often, MTB treatment recommendations differ from those in the NGS reports. In this study, we analyze the discordance between these recommendations and the rationales behind the discordances, in a non-high-income setting, with international input to evaluate the necessity of MTB in clinical practice. METHODS: We collated data from MTB that were virtually hosted in Chennai, India. We included patients with malignancies who had NGS reports on solid tissue or liquid biopsies, and excluded those with incomplete data. MTB forms and NGS reports of each clinical case were analyzed and evaluated for recommendation concordance. Concordance was defined as an agreement between the first recommendation in the MTB forms and the therapeutic recommendations suggested in the NGS report. Discordance was the absence of the said agreement. The rationales for discordance were identified and documented. RESULTS: Seventy MTB reports were analyzed with 49 cases meeting the inclusion criteria. The recommendation discordance was 49% (24 of 49). Discordant recommendations were mainly due to low level of evidence for the drug (75% of cases). CONCLUSION: The discordance between MTB and NGS vendor recommendations highlights the clinical utility of MTB. The educational experiences provided by this initiative are an example of how virtual academic collaborations can enhance patient care and provider education across geographic borders.


Assuntos
Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão , Índia , Oncologia , Sequenciamento de Nucleotídeos em Larga Escala
12.
Oncologist ; 18(6): 675-84, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23740934

RESUMO

Metastasis to the central nervous system (CNS) is a devastating neurological complication of systemic cancer. Brain metastases from breast cancer have been documented to occur in approximately 10%-16% of cases over the natural course of the disease with leptomeningeal metastases occurring in approximately 2%-5% of cases of breast cancer. CNS metastases among women with breast cancer tend to occur among those who are younger, have larger tumors, and have a more aggressive histological subtype such as the triple negative and HER2-positive subtypes. Treatment of CNS metastases involves various combinations of whole brain radiation therapy, surgery, stereotactic radiosurgery, and chemotherapy. We will discuss the progress made in the treatment and prevention of breast cancer-associated CNS metastases and will delve into the biological underpinnings of CNS metastases including evaluating the role of breast tumor subtype on the incidence, natural history, prognostic outcome, and impact of therapeutic efficacy.


Assuntos
Neoplasias da Mama/patologia , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias Meníngeas/patologia , Barreira Hematoencefálica , Neoplasias da Mama/terapia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/cirurgia , Feminino , Humanos , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/cirurgia , Prognóstico , Radiocirurgia , Receptor ErbB-2/genética , Resultado do Tratamento
13.
Case Rep Oncol ; 16(1): 1451-1459, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028569

RESUMO

Introduction: The burden of melanoma is increasing globally. Despite the use of immunotherapy and targeted therapy, the prognosis of metastatic melanoma remains relatively poor. The integration of comprehensive molecular profiling can lead to the detection of actionable biomarkers and the expansion of treatment options, thereby prolonging cancer patient survival. Case Presentation: We herein present the case of a female 54-year-old patient diagnosed with melanoma of the right knee, for which she underwent surgery. Patient showed progression of disease after 10 cycles of adjuvant nivolumab. Ipilimumab (1 mg/kg every 3 weeks) was added to the treatment regimen but no clinical improvement was observed. Molecular profiling was conducted based on patient tissue, and an ANXA2-NTRK3 fusion was detected in the tumor. This specific fusion has not been previously reported; however, it is in-frame and similar to other known oncogenic NTRK fusions. At the time of entrectinib initiation, the patient had clear disease progression on the right leg on standard of care immunotherapy. She was commenced on entrectinib 200 mg once daily for 2 weeks. Dose escalation was attempted, and treatment intensity was managed based on drug tolerability. Good treatment response was observed on laboratory and radiologic parameters. As of September 2023, i.e., 2.5 years after treatment initiation, patient disease continues to be controlled with entrectinib. Conclusion: Profiling of advanced tumors is important to determine the presence of agnostic markers that can be targeted and ultimately improve the prognostic outcome of patients after the failure of standard of care.

14.
Cancers (Basel) ; 15(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37760527

RESUMO

Background: CDK4/6-inhibitors have demonstrated similar efficacy and are considered an effective first-line endocrine treatment of patients with hormone-receptor positive (HR+)/human-epidermal-growth-factor-receptor-2 negative (HER2-) metastatic breast cancer (MBC) in the endpoint of progression-free survival (PFS). Amongst these, palbociclib was first to achieve regulatory approval, followed subsequently by ribociclib and abemaciclib. However, recent updates of overall survival (OS) showed inconsistencies in the OS benefit for palbociclib compared with the other two CDK4/6-inhibitors. With the lack of head-to-head comparison studies, our study sought to compare indirect survival outcomes between CDK4/6-inhibitors in this setting using a novel reconstructive algorithm. Methods: Phase III randomized trials comparing first-line aromatase inhibitor with/without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2- MBC were identified through systemic review and literature search of online archives of published manuscripts and conference proceedings. A graphical reconstructive algorithm was utilized to retrieve time-to-event data from reported Kaplan-Meier OS and PFS plots to allow for comparison of survival outcomes. Survival analyses were conducted with Cox proportional-hazards model with a shared-frailty term. Results: Three randomized phase III trials-PALOMA-2, MONALEESA-2 and MONARCH-3-comprising 1827 patients were included. Indirect pairwise comparisons of all CDK4/6-inhibitors showed no significant PFS differences (all p > 0.05). Likewise, indirect treatment comparison between ribociclib vs. palbociclib (one-stage: HR = 0.903, 95%-CI: 0.746-1.094, p = 0.297), abemaciclib vs. palbociclib (one-stage: HR = 0.843, 95%-CI: 0.690-1.030, p = 0.094) and abemaciclib vs. ribociclib (one-stage: HR = 0.933, 95%-CI: 0.753-1.157, p = 0.528) failed to demonstrate a significant OS difference. Conclusions: Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitors in post-menopausal patients with HR+/HER2- MBC.

15.
Cancer ; 118(19): 4652-9, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22359359

RESUMO

BACKGROUND: This retrospective study sought to define the incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer (TNBC). METHODS: A total of 2448 patients with stage I through III TNBC who were diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. The Kaplan-Meier product limit method was used to compute survival following a diagnosis of brain metastases. RESULTS: At a median follow-up of 39 months, 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95% confidence interval [CI] = 2.9%-4.5%) and 5.4% (95% CI = 4.4%-6.5%), respectively. Among patients with stage I, II, and III disease, the 2-year cumulative incidence of brain metastases was 0.8%, 3.1%, and 8%, respectively (P < .0001). The 5-year cumulative incidence was 2.8%, 4.6%, and 9.6% among patients with stage I, II, and III disease, respectively (P < .0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (hazards ratio = 3.51; 95% CI = 1.85-6.67; P = .0001) compared to patients with stage I disease. Those with stage II disease had a nonsignificant increased risk of developing brain metastases as a first site of recurrence (hazards ratio = 1.61; 95% CI = 0.92-2.81; P = .10) compared with patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range, 5.7-9.4 months). CONCLUSIONS: Patients with nonmetastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort in which to research preventive strategies.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/secundário , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Neoplasias Encefálicas/epidemiologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Incidência , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Estudos Retrospectivos , Estados Unidos/epidemiologia
16.
Cancer ; 118(11): 2780-6, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22614656

RESUMO

BACKGROUND: The US Food and Drug Administration's (FDA's) recent decision to remove the indication of bevacizumab for metastatic breast cancer (MBC) has fueled a debate in the breast cancer community. We conducted a survey to assess the perception of health care workers involved in the management of women with MBC on the FDA's decision to ascertain how it will affect practice and to determine how bevacizumab is commonly used in the community for MBC. METHODS: E-mails were sent out between September and November 2010 using a database of 3000 addresses maintained by the United Arab Emirates Cancer Congress. Individuals working for Roche or Genentech were excluded. The survey consisted of 22 questions that were divided into 3 parts addressing each participant's demographic profile, their opinion of the FDA's decision, and the typical use of bevacizumab in the community in the setting of MBC. RESULTS: A total of 564 participants were included in the final analysis, contributing to an 18.8% response rate. Of these participants, 14.6% were from the United States, 7.8% were from Canada, 31.1% were from Europe, 2.0% were from the United Arab Emirates, 11.1% were from Asia, and 33.3% were from other countries. The majority of participants believed progression-free survival to be a surrogate for overall survival, that cost played a role in the FDA's decision, and that the decision would adversely affect the future of newer drugs currently being investigated for MBC. The majority of participants indicated that they would use bevacizumab for triple receptor-negative MBC (46.5%), would use it in a first-line setting (44.7%), and would use it in combination with paclitaxel (51.9%). CONCLUSION: Our survey results highlight the discord between the opinion of community oncologists and the FDA's recent decision to withdraw the indication of bevacizumab for MBC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Atitude do Pessoal de Saúde , Neoplasias da Mama/tratamento farmacológico , Aprovação de Drogas , Pesquisas sobre Atenção à Saúde , Oncologia , Adulto , Anticorpos Monoclonais Humanizados/economia , Bevacizumab , Neoplasias da Mama/patologia , Uso de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estados Unidos , United States Food and Drug Administration
17.
Cancer ; 118(20): 4936-43, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22511276

RESUMO

BACKGROUND: Previous studies have shown that hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status influence the outcome of locoregional treatments. However, the interrelationship of these factors with trastuzumab is unclear. In this study, the role of HR and HER2 status on the locoregional benefit of trastuzumab treatment was investigated in patients with nonmetastatic breast cancer. METHODS: Locoregional outcomes of 5683 women treated at The University of Texas MD Anderson Cancer Center from 2000 to 2008 for invasive breast cancer were analyzed using Kaplan-Meier and Cox regression methods to compare 6 subgroups: HR-positive (HR+)/HER2-negative (HER2-), HR-/HER2- (triple-negative), HR+/HER2+ with or without trastuzumab, and HR-/HER2+ with or without trastuzumab. RESULTS: Overall, locoregional recurrence (LRR) was 5% at 5 years among patients with HER2+ disease. Patients with HR+/HER2+ disease treated with trastuzumab had half the rate of LRR as patients who did not receive trastuzumab, whereas patients with HR-/HER2+ disease had similar rates of LRR regardless of trastuzumab treatment. On Cox regression analysis comparing LRR risk to the cohort with HR+/HER2- disease, only the HR+/HER2+ cohort treated with trastuzumab had similar LRR risk (hazard ratio = 1.24, 95% confidence interval = 0.56-2.73, P = .591). All other subgroups, including the HR+/HER2+ cohort who did not receive trastuzumab, had significantly worse outcomes. LRR risk was highest among patients with triple-negative disease (hazard ratio = 4.73, 95% confidence interval = 3.42-6.54, P < .001). CONCLUSIONS: Among patients with HR+/HER2+ disease, treatment with trastuzumab reduces LRR risk to the more favorable outcome of patients with HR+/HER2- disease. In contrast, the increased LRR risk among patients with HR-/HER2+ disease remains despite treatment with trastuzumab. Additional locoregional strategies are needed in this subgroup of patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Trastuzumab , Resultado do Tratamento
18.
Breast Cancer Res Treat ; 126(1): 185-92, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20711652

RESUMO

The objective of this study is to define the survival outcomes associated with distinct molecular phenotypes defined by immunohistochemical staining of paraffin-embedded tissues among invasive breast cancer cases identified from the Nurses' Health Study (NHS). Tissue microarrays were constructed from archived tissue blocks of women diagnosed with breast cancer in the NHS (1976-1997). Invasive non-metastatic breast cancer tumors (n = 1,945) were classified into 1 of 5 molecular phenotypes based on immunohistochemistry assays for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and grade. Survival outcomes were estimated using the Kaplan-Meier product limit method. Cox-proportional hazards models were fitted to determine the association of molecular phenotype with survival outcomes after adjusting for covariates. 1,279 (65.8%) tumors were classified as luminal A, 279 (14.3%) as luminal B, 95 (4.9%) as HER2 type, 203 (10.4%) as basal-like and 89 (4.6%) tumors were unclassified. The 5-year breast cancer-specific survival estimates for women with luminal A, luminal B, HER2-type, basal-like and unclassified tumors were 96, 88, 81, 89 and 85%, respectively. In the multivariable model, compared to cases with luminal A tumors, cases with luminal B (HR 1.90, 95% CI 1.33-2.71), HER2-type (HR 1.36, 95% CI 0.87-2.12), basal-like (HR 1.58, 95% CI 1.05-2.39) and unclassified (HR 1.38, 95% CI 0.87-2.20) tumors had higher hazard of breast cancer death. Similar trends were observed for both overall and recurrence-free survival. In conclusion, compared to women who have luminal A tumors those with luminal B, HER2-type, basal-like and unclassified tumors had a worse prognosis, when tumor subtype was defined by immunohistochemistry. This method may provide a cost-effective means of determining prognosis in the clinical setting.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Adulto , Neoplasias da Mama/terapia , Estudos de Coortes , Receptores ErbB/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Queratina-5/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida , Análise Serial de Tecidos
19.
Oncology (Williston Park) ; 25(3): 264-70, 273, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21548470

RESUMO

Inflammatory breast cancer (IBC) is a rare and aggressive subtype of locally advanced breast cancer (LABC). Its diagnosis is primarily clinical; however, a pathological confirmation of invasive cancer is required. Historically, IBC was a uniformly fatal disease. A major advance in the last three decades has been the introduction of a multidisciplinary approach to the management of this aggressive disease, incorporating pre-operative chemotherapy, surgery, and radiation therapy; this approach has significantly improved survival. Our review focuses on the progress made in the field of IBC research over the last decade, with particular attention to advances in the areas of epidemiology, molecular biology, arid clinical management.


Assuntos
Neoplasias Inflamatórias Mamárias/diagnóstico , Neoplasias Inflamatórias Mamárias/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/mortalidade , Taxa de Sobrevida
20.
Ann Transl Med ; 9(14): 1175, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430616

RESUMO

BACKGROUND: Clinical practice guidelines are an essential tool for translating evidence into practice. Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist assists to guide the reporting in guidelines. We used RIGHT to assess the reporting completeness and quality of guidelines on colorectal cancer (CRC). METHODS: We searched the electronic databases Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) from January 1st, 2018 to December 1st, 2020 for guidelines on CRC. Websites of guideline development organizations were also searched. Two investigators assessed the reporting quality of the included guidelines, and calculated the numbers of guidelines that were compliant with each RIGHT checklist item and the mean proportions of reported items for each of the seven RIGHT checklist domains. RESULTS: Twenty-seven colorectal guidelines were included. The proportions of reported items in each RIGHT domain were 71.0% for Basic information, 66.2% for Background, 45.9% for Evidence, 68.8% for Recommendations, 24.1% for Review and quality assurance, 33.3% for Funding and declaration and management of interests, and 40.7% for Other information. CONCLUSIONS: The reporting quality of colorectal guidelines was moderate. A systematic use of the RIGHT checklist during the development process could improve the reporting quality of guidelines in the future.

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