ABSTRACT
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.
Subject(s)
Aminopyridines/pharmacology , Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Molecular Targeted Therapy/methods , Morpholines/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Animals , Breast Neoplasms/metabolism , Female , Humans , Mice , Signal Transduction/drug effectsABSTRACT
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.
Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/prevention & control , Medical Oncology , Practice Guidelines as Topic/standards , Societies, Medical , Female , Humans , Neoplasm StagingABSTRACT
The increase in life expectancy in the western world means that we are faced with patients diagnosed with breast cancer in old age with increasing frequency. The management of these cases is a challenge for the oncologist, who must take into account the conditions associated with advanced age and the lack of trials in this population. In this review, we addressed the incorporation of geriatric assessment methods that may be useful in making decisions, the particular biological characteristics of breast cancer in elderly patients and their treatment in both localized and advanced disease. Finally, we collected recommendations based on scientific evidence regarding the monitoring and life-style after finishing treatment.
Subject(s)
Breast Neoplasms/therapy , Geriatric Assessment/methods , Aged , Aged, 80 and over , Female , HumansABSTRACT
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.
Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Lobular/diagnosis , Magnetic Resonance Imaging , Adult , Aged , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Lobular/metabolism , Early Detection of Cancer , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Survival RateABSTRACT
The following manuscript summarises the content of the Breast Symposium that was held in May 2008 in Barcelona in which four controversies regarding the management of breast cancer were discussed. The design of the symposium included two speakers per controversy, one in favour and one diverging, and the audience had to vote before and after the presentations to assess changes in the participants' views. The four controversies included: (1) the role of non-conventional predictive factors in selecting treatment for breast cancer; (2) the role of surgery in disseminated disease; (3) are taxanes indicated in the adjuvant treatment of patients with lymph-node-negative disease?; (4) is treatment with tamoxifen (TAM) always required after surgery in patients with ductal carcinoma in situ (DCIS)? The symposium concluded with the presentation titled: 'Features of a well designed clinical trial in the adjuvant treatment of breast cancer'.
Subject(s)
Breast Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Combined Modality Therapy , Female , Humans , MastectomyABSTRACT
INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Breast Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/biosynthesis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , DNA Topoisomerases, Type II/biosynthesis , DNA-Binding Proteins/biosynthesis , Docetaxel , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Immunohistochemistry , Inhibitor of Apoptosis Proteins , Microtubule-Associated Proteins/biosynthesis , Middle Aged , Neoplasm Staging , Proliferating Cell Nuclear Antigen/biosynthesis , Survivin , Taxoids/administration & dosage , Taxoids/adverse effectsABSTRACT
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.
Subject(s)
Breast Neoplasms/therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Female , Gene Expression Regulation, Neoplastic , Genes, erbB-2/genetics , Humans , Neoadjuvant Therapy , Ovariectomy , Sentinel Lymph Node Biopsy , TrastuzumabABSTRACT
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.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cyclophosphamide/therapeutic use , Deoxycytidine/analogs & derivatives , Doxorubicin/therapeutic use , Taxoids/administration & dosage , Adult , Aged , Chemotherapy, Adjuvant , Deoxycytidine/administration & dosage , Docetaxel , Drug Administration Schedule , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , GemcitabineABSTRACT
Experimental leptospirosis was reproduced in golden Syrian hamsters (Mesocricetus aureatus). Evaluation of three Leptospira serogroups (canicola, icterohaemorrhagiae and pomona) was carried out regarding their virulence, production of symptoms and lethal activity. Macroscopic and microscopic studies of tissue lesions were also made. Animals were inoculated with 3.75 x 10(6) to 6 x 10(7) bacteria through the intraperitoneal (IP) route. The clinical development of the disease in Syrian hamsters was characterized by the presence of general symptoms between the third and fifth day after inoculation. With highly virulent strains, the distinctive clinical picture occurred and death followed before the seventh day. The strain of the pomona serogroup proved to be more virulent than those of the other serogroups and produced the most florid picture of the disease. Pathogenic aspects of this process were also studied.
Subject(s)
Disease Models, Animal , Leptospirosis/pathology , Mesocricetus/microbiology , Animals , Cricetinae , MaleABSTRACT
Con el objeto de valorar las propiedades profilácticas de la teofilina de acción prolongada y el ketotifeno, se realizó un estudio comparativo y cruzado, con 29 niños de la consulta de pediatría y de emergencia del Departamento de Pediatría del Hospital General "José Ignacio Baldó" de Caracas, de febrero a noviembre de 1986. Todos los niños recibieron ambos medicamentos en un esquema secuencial cruzado, ciego. Los pacientes estaban comprendidos en edades de 5 a 11 años, 19 masculinos y 10 femeninos; la mayoría con asma severa y compromiso de la función pulmonar. Durante el periodo de tratamiento con la teofilina de acción prolongada se observó mayor protección frente a los alergenos conocidos (75%), mayor número de pacientes con períodos libre de crisis, reducción de la frecuencia y severidad de la crisis (29%), menos hospitalizaciones (33.33%), reducción del uso de broncodilatadores inhalados (40%), mejoría de la función pulmonar y buena tolerancia, estos dos últimos resultados fueron similares al periodo con ketotifeno. Su mayor eficacia fue ante las formas moderadas y severas de asma. Los mejores resultados fueron con la teofilina de acción prolongada, la cual presenta mayor acción profiláctica antiasmática, cuando se compara con el ketotifeno
Subject(s)
Child, Preschool , Child , Humans , Male , Female , Asthma/drug therapy , Theophylline/therapeutic useABSTRACT
We report 41 patients with myocardial infarction who were less than forty years old and that had been studied by coronary angiography. 97.5% were male mostly in their thirties. Coronary risk factors in this group were similar to the old one; excepting for mental stress present in 75% of our patients. There was not predominant infarction site. We observed different disturbances of the cardiac rhythm but no patient had congestive heart failure or cardiogenic shock. Mortality due to the infarct itself was none .61% of the cases had univascular lesions or normal coronary angiography and only 12% had trivascular lesions. The patients with normal coronary angiography had no significant difference in the mayor coronary risk factors and in our group we found patients with arterial hypertension, hyperlipidemia, cigarette smoking and obesity. We suggest that mental stress is an important coronary risk factor; the evolution of these patients is favorable and the mortality is low as compared with previous reports.