Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer.

Purpose: This multicenter, randomized, double-blind, phase II study assessed safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC).

Patients And Methods: Women with MBC were randomly assigned 2:1 to receive docetaxel 80 mg/m2 once every 3 weeks plus axitinib 5 mg twice per day (combination arm) or placebo (placebo arm), following a lead-in phase I trial. The primary end point was time to progression (TTP).

PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer.

The purpose of this work was to determine whether there are differences in PIK3CA mutation status and PTEN protein expression between primary and matched metastatic breast tumors as this could influence patient management. Paraffin sections of 50 μm were used for DNA extraction and slides of 3 μm for immunohistochemistry (IHC) and FISH. Estrogen receptor, progesterone receptor, and HER2 IHC were repeated in a central laboratory for both primary tumors and metastases.

Etiology of Kienböck disease.

The etiology of Kienböck disease is still unknown and, consequently, the ideal treatment is in doubt. Many different hypotheses have been suggested. There are reasons to believe that there are mechanical, vascular, and metabolic factors predisposing to the disease, and probably some factors triggering the development of the process.

Adjuvant docetaxel for high-risk, node-negative breast cancer.

Background: A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined.

Methods: We randomly assigned 1060 women with axillary-node-negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St.

Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper.

Background: Comorbidities and risk factors likely to complicate treatment are common in elderly cancer patients. Anthracyclines remain the cornerstone of first-line therapy for non-Hodgkin's lymphoma (NHL) and metastatic and early breast cancer but can cause congestive heart failure. Elderly patients are at increased risk of this event and measures to reduce it should be considered.

The Sauvé-Kapandji procedure: indications and tips for surgical success.

Arthrodesis is the most reliable and durable surgical procedure for the treatment of a joint disorder, with the main disadvantage of loss of motion of the fused joint. The distal radioulnar joint can be arthrodesed, while forearm pronation and supination are maintained or even improved by creating a pseudoarthrosis of the ulna just proximal to the arthrodesis. This is known as the Sauvé-Kapandji procedure.

Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer.

Purpose: We examined in a prospective, randomized, international clinical trial the performance of a previously defined 30-gene predictor (DLDA-30) of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide (T/FAC) chemotherapy, and assessed if DLDA-30 also predicts increased sensitivity to FAC-only chemotherapy. We compared the pCR rates after T/FAC versus FACx6 preoperative chemotherapy. We also did an exploratory analysis to identify novel candidate genes that differentially predict response in the two treatment arms.

Phase I study of oral vinorelbine and capecitabine in patients with metastatic breast cancer.

Background: To determine the recommended doses of oral vinorelbine (VN) and capecitabine (C) in metastatic breast cancer.

Patients And Methods: Eighteen patients with metastatic breast cancer received oral VN (on days 1 and 8) and C (on days 1 to 14) every three weeks at one of four dose levels: I) 60 mg/m(2) and 1650 mg/m(2)/day; II) 70 mg/m(2) and 1650 mg/m(2)/day; III) 70 mg/m(2) and 2000 mg/m(2)/day; IV) 80 mg/m(2) and 2000 mg/m(2)/day, respectively. The primary endpoint was to determine the recommended doses for the combination of oral VN and C in metastatic breast cancer.

Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer.

Purpose: To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development.

Patients And Methods: The frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node-negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from > 400 breast cancer samples.

Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer.

Introduction: Accumulating evidence suggests that both levels and activity of the estrogen receptor (ER) and the progesterone receptor (PR) are dramatically influenced by growth-factor receptor (GFR) signaling pathways, and that this crosstalk is a major determinant of both breast cancer progression and response to therapy. The phosphatidylinositol 3-kinase (PI3K) pathway, a key mediator of GFR signaling, is one of the most altered pathways in breast cancer. We thus examined whether deregulated PI3K signaling in luminal ER+ breast tumors is associated with ER level and activity and intrinsic molecular subtype.

Current controversies in the management of breast cancer.

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'.

Mechanisms of resistance to hormonal treatment in breast cancer.

Endocrine therapy is a cornerstone in hormone-dependent breast cancer treatment. Despite the effectiveness of this type of treatment, a significant percentage of tumours develop resistance, and hence, patients relapse. This raises the question of which mechanisms are activated by hormone-dependent tumours to become resistant to antihormonal therapy.

Current perspectives of treatment of ductal carcinoma in situ.

DCIS is a genetically diverse group of diseases with different prognosis. The similarities between DCIS and ductal infiltrating carcinoma (DIC) suggest that the key step in tumorigenesis is the transformation from high grade ductal hyperplasia to DCIS. The prognostic factors of DCIS include anatomo-pathologic factors, age and molecular factors.

Gastrointestinal targets of appetite regulation in humans.

The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions - and related biomarkers - implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies.

Appetite control: methodological aspects of the evaluation of foods.

This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report.

Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort.

Background: The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.

Methods: We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil.

Supportive care for patients with early breast cancer.

Breast cancer treatment currently requires the joint efforts of a multidisciplinary team to effectively combine chemotherapy, hormone therapy, biological agents, surgery and radiation therapy when needed. To develop such a treatment plan, it is important to know the benefits as well as the potential toxic effects of each therapy. Thus, many patients with early breast cancer complain of collateral adverse events such as fatigue, nausea, vomiting, loss of libido, hot flashes, night sweats or neuropathy due to the complex therapies they are receiving.

Practical prognostic index for patients with metastatic recurrent breast cancer: retrospective analysis of 2,322 patients from the GEICAM Spanish El Alamo Register.

Women with recurrent metastatic breast cancer from a Spanish hospital registry (El Alamo, GEICAM) were analyzed in order to identify the most helpful prognostic factors to predict survival and to ultimately construct a practical prognostic index. The inclusion criteria covered women patients diagnosed with operable invasive breast cancer who had metastatic recurrence between 1990 and 1997 in GEICAM hospitals. Patients with stage IV breast cancer at initial diagnosis or with isolated loco-regional recurrence were excluded from this analysis.

Triple-negative breast cancer: molecular features, pathogenesis, treatment and current lines of research.

Breast cancer is a heterogeneous disease with different morphologies, molecular profiles, clinical behaviour and response to therapy. The triple negative is a particular type of breast cancer defined by absence of oestrogen and progesterone receptor expression as well as absence of ERBB2 amplification. It is characterized by its biological aggressiveness, worse prognosis and lack of a therapeutic target in contrast with hormonal receptor positive and ERBB2+ breast cancers.

Gemcitabine and capecitabine in previously anthracycline-treated metastatic breast cancer: a multicenter phase II study (SOLTI 0301 trial).

Background: On the basis of clinical activity of capecitabine and gemcitabine for metastatic breast cancer, we carried out a multicenter phase II clinical trial on the combination of these two agents in advanced anthracycline-pretreated breast cancer patients. Main objectives were to assess its efficacy and safety profile.

Patients And Methods: Seventy-six anthracycline-pretreated breast cancer patients were evaluated and were stratified according to previous treatment of advanced disease (group-1: not previously treated and group-2: previously treated).

Outcome differences between patients with node-negative breast cancer classified according to the st. Gallen risk categories.

Purpose: The purpose of this study was to compare the 2007 St. Gallen risk categories with the outcomes of patients with node-negative breast cancer (NNBC).

Patients And Methods: We retrospectively reviewed the medical records of 1500 women with pathologically T1-T3 NNBC treated at the Clinic Hospital, Valencia University (Spain) from 1982 to 2000.

The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial.

Background: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy.

Patients And Methods: This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed.

Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients: the impact of addition of taxanes to anthracycline-based regimens.

Adjuvant chemotherapy prolongs survival in patients with breast cancer, but it also causes side effects such as ovarian-function suppression. The incidence of chemotherapy-induced amenorrhea (CIA) varies depending on the patients' age, dose and the type of chemotherapy that they receive. CIA produced by anthracycline-based regimens has been widely studied, but less is known about the incidence of CIA caused by the combined use of taxanes and anthracyclines.

AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer.

Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth.