RESUMO
Aberrations in the PI3K signaling pathway are frequently observed in patients with breast cancer. Because of that, PI3K inhibitors are attractive options for the treatment of breast cancer because PI3K is the most proximal component of the pathway other than receptor tyrosine kinases. Buparlisib is a potent and highly specific oral pan-class I PI3K inhibitor, which is currently under investigation in patients with breast cancer. In this article, we describe the PI3K signaling pathway, the prognostic value of PI3K pathway mutations, as well as the mechanism of action of buparlisib. Lastly, we discuss preliminary results of preclinical and clinical studies showing the efficacy and safety profile of this agent in breast cancer patients.
Assuntos
Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Terapia de Alvo Molecular/métodos , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Neoplasias da Mama/metabolismo , Feminino , Humanos , Camundongos , Transdução de Sinais/efeitos dos fármacosRESUMO
Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Oncologia , Guias de Prática Clínica como Assunto/normas , Sociedades Médicas , Feminino , Humanos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Use of breast magnetic resonance imaging (MRI) to detect breast cancer has generated significant debate. We analyze the role of breast MRI in the detection of additional disease and the need to perform additional biopsies in early breast carcinoma patients. In addition, we correlate the detection of new foci with tumor pathological features. METHODS: Early breast carcinoma patients that had undergone an MRI as well as a mammography as diagnostic procedures were included in the study. The following pathologic features were studied: carcinoma type, histological grade, estrogen receptors (ER), progesterone receptors (PR), HER2 and Ki67. Univariate analysis was conducted to ascertain significant correlation among detection of new foci and each of the tumor pathological features. RESULTS: Data from 98 patients have been analyzed: median age 49 years (range 35-79); carcinoma type: (a) infiltrative ductal carcinoma (n = 73, 74 %), (b) infiltrative lobular cancer (n = 12, 12 %), (c) ductal carcinoma in situ (n = 6, 6 %); amplified HER2 (n = 18, 18 %); grade III (n = 33, 33 %); Ki67 ≥ 25 % (n = 33, 33.67 %); positive ER and PR (n = 79, 80 %); triple negative tumors (n = 8, 8 %). MRI detected additional disease in 38 cases (39.58 %), and 20 led to an additional biopsy (20.4 %). Thirty-eight patients (39 %) underwent mastectomy. We found a statistically significant correlation between new foci in MRI and high Ki67 ≥ 25 % (p < 0.005). No other statistically significant correlation was established. CONCLUSION: MRI detected additional disease in 39 % cases, requiring an additional biopsy 20 %. Tumors with high proliferative index were significantly correlated with the detection of new foci in MRI.
Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Lobular/diagnóstico , Imageamento por Ressonância Magnética , Adulto , Idoso , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Lobular/metabolismo , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Medical professionals in general, and medical oncologists in particular, have highly stressful practices because they are under constant pressure to have the highest-quality, up-to-date evidence available in order to make the right decision for each individual patient. From a practical point of view, being updated on oncological and other medical specialties may seem an insurmountable task because the number of scientific publications has increased dramatically. The use of systematic reviews of randomised controlled trials or the application of results obtained from high-quality randomised controlled trials are some of the most common ways to address this need. Unfortunately, they do not cover all complex clinical situations that the majority of medical oncologists face in their outpatient consultations. In this review, we report the conclusions achieved in a multiexpert meeting where five important controversies in the treatment of breast cancer were analysed. Five highly experienced medical oncologists were required to defend an affirmative answer and another five were required to defend a negative answer for each of the clinical questions. After that, a one-day meeting was organised to debate each clinical question and to reach a consensus. We report here the content of this multi-expert meeting along with the conclusions drawn.
Assuntos
Neoplasias da Mama/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Regulação Neoplásica da Expressão Gênica , Genes erbB-2/genética , Humanos , Terapia Neoadjuvante , Ovariectomia , Biópsia de Linfonodo Sentinela , TrastuzumabRESUMO
INTRODUCTION: The purpose of this phase II study was to evaluate the efficacy and safety of neoadjuvant docetaxel/gemcitabine treatment in a biweekly regimen. MATERIALS AND METHODS: Patients with stage II/III breast cancer were treated with docetaxel (65 mg/m(2)) followed by gemcitabine (2500 mg/m(2)) every 2 weeks for 6 cycles. Patients with a clinical response or stable disease underwent mastectomy or breast-conserving surgery plus axillary dissection. After surgery, patients received 4 cycles of standard doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. RESULTS: Thirty-five patients were included in the trial. The overall response rate was 71.4% (95% CI: 53.7-85.4), with 8 complete and 17 partial responses. Breast conservation was possible in 59% of the patients. Toxicity was manageable. CONCLUSIONS: We consider biweekly docetaxel and gemcitabine could be an active and tolerable regimen option in the neoadjuvant setting sequentially with standard adjuvant doxorubicin-cyclophosphamide in patients with stage II or III breast cancer.