Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer.

Purpose: In KATHERINE, adjuvant T-DM1 reduced risk of disease recurrence or death by 50% compared with trastuzumab in patients with residual invasive breast cancer after neoadjuvant therapy (NAT) comprised of HER2-targeted therapy and chemotherapy. This analysis aimed to identify biomarkers of response and differences in biomarker expression before and after NAT.

Experimental Design: Exploratory analyses investigated the relationship between invasive disease-free survival (IDFS) and HER2 protein expression/gene amplification, PIK3CA hotspot mutations, and gene expression of HER2, PD-L1, CD8, predefined immune signatures, and Prediction Analysis of Microarray 50 intrinsic molecular subtypes, classified by Absolute Intrinsic Molecular Subtyping.

Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE).

Background: KRISTINE is an open-label, phase III study of trastuzumab emtansine + pertuzumab (T-DM1 + P) versus docetaxel + carboplatin + trastuzumab + pertuzumab (TCH + P) in patients with HER2-positive, stage II-III breast cancer. We investigated the association of biomarkers with clinical outcomes in KRISTINE.

Methods: Patients were randomized to receive neoadjuvant T-DM1 + P or TCH + P and assessed for pathologic complete response (pCR; ypT0/is, ypN0).

ASTEFANIA: adjuvant ado-trastuzumab emtansine and atezolizumab for high-risk, HER2-positive breast cancer.

There is a strong rationale for combining HER2-targeted therapies with cancer immunotherapy to increase efficacy in breast cancer, particularly in the early-stage setting, where the immune system has not been weakened by heavy pretreatment. ASTEFANIA aims to evaluate the efficacy of adjuvant atezolizumab in combination with ado-trastuzumab emtansine in patients with high-risk, HER2-positive early breast cancer and residual disease following HER2-based neoadjuvant therapy. Eligible patients will be randomized to receive ado-trastuzumab emtansine in combination with either atezolizumab or placebo for 14 cycles within 12 weeks of primary surgery.

Adjuvant trastuzumab emtansine in HER2-positive breast cancer patients with HER2-negative residual invasive disease in KATHERINE.

Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the pre-treatment core biopsy with HER2-negative central testing on their corresponding surgical specimen after neoadjuvant treatment. In the 70/845 (8.

Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study.

Purpose: We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1).

Methods: The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor-negative, and tumor > 2.0 cm).

Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE.

Background: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses.

Patients And Methods: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab).

Patient-reported outcomes from KATHERINE: A phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer.

Background: The phase 3 KATHERINE trial demonstrated significantly improved invasive disease-free survival with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy.

Methods: Patients who received taxane- and trastuzumab-containing neoadjuvant therapy (with/without anthracyclines) and had residual invasive disease (breast and/or axillary nodes) at surgery were randomly assigned to 14 cycles of adjuvant T-DM1 (3.6 mg/kg intravenously every 3 weeks) or trastuzumab (6 mg/kg intravenously every 3 weeks).

Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study.

Purpose: The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% 55.

Lymphoma and Epstein-Barr virus DNA in blood during interleukin-2 therapy in antiretroviral-naïve HIV-1-infected patients: a substudy of the ANRS 119 trial.

Objectives: Interleukin-2 (IL-2) therapy increased CD4 cell counts and delayed antiretroviral therapy (ART) initiation in HIV-infected patients in the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) 119 trial. However, four cases of lymphoma were reported. Epstein-Barr virus (EBV) replication is associated with an increased risk of lymphoma in immunocompromised patients.

Long-term in vivo imaging of viscoelastic properties of the mouse brain after controlled cortical impact.

Traumatic brain injury (TBI) presents a variety of causes and symptoms, thus making the development of reliable diagnostic methods and therapeutic treatments challenging. Magnetic resonance elastography (MRE) is a technique that allows for a noninvasive assessment of the mechanical properties of soft biological tissue, such as tissue stiffness, storage modulus, and loss modulus. Importantly, by quantifying the changes in the stiffness of tissue that is often associated with disease, MRE is able to detect tissue pathologies at early stages.

Magnetic resonance elastography methodology for the evaluation of tissue engineered construct growth.

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use of destructive assessment is not acceptable. A proposed alternative is the use of an imaging process called magnetic resonance elastography. Elastography is a nondestructive method for determining the engineered outcome by measuring local mechanical property values (i.

Microscopic magnetic resonance elastography of traumatic brain injury model.

Traumatic brain injury (TBI) is a major cause of death and disability for which there is no cure. One of the issues inhibiting clinical trial success is the lack of targeting specific patient populations due to inconsistencies between clinical diagnostic tools and underlying pathophysiology. The development of reliable, noninvasive markers of TBI severity and injury mechanisms may better identify these populations, thereby improving clinical trial design.

Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia.

Background: The emergence of integrase strand-transfer inhibitor (INSTI) resistance-associated mutations was examined in patients with low-level viremia after switching from enfuvirtide to raltegravir in the ANRS 138-Easier trial.

Methods: Integrase genes of plasma virus from raltegravir-treated patients in the Easier trial with low-level viremia (50-500 copies/ml) were sequenced to determine INSTI resistance-associated mutations. Baseline viral load, baseline and nadir CD4 cell count, antiretroviral treatment, genotypic susceptibility score, level of viremia and degree of treatment adherence during the study period were also analyzed.

Impact on health-related quality of life of a switch from enfuvirtide to raltegravir among multidrug-resistant HIV-1-infected patients: a randomized open-label trial (EASIER-ANRS 138).

Background: among multidrug-resistant HIV-1-infected patients, enfuvirtide has demonstrated sustained efficacy, but long-term use is inconvenient due to twice-daily subcutaneous injections which often induce injection-site reactions. We investigated whether a switch from enfuvirtide to raltegravir, an orally available HIV-integrase inhibitor, may improve health-related quality of life (HRQoL).

Methods: 170 multidrug-resistant HIV-1-infected patients who were receiving enfuvirtide-based regimens were randomised to the maintenance of enfuvirtide or the switch to raltegravir at day 0.

CXCR4 expression in early breast cancer and risk of distant recurrence.

Background: Chemokine receptor 4 (CXCR4) has been demonstrated to have a critical role in the early metastatic process. The aim of this study was to evaluate the prognostic value of CXCR4 expression in primary breast tumors and describe correlations with the occurrence of metastasis in organs expressing the CXCR4 ligand stromal cell-derived factor 1 (i.e.

[Prevalence of elevated serum CA 15-3 at time of metastatic relapse of breast cancer and correlation with hormone receptor status].

CA15-3, a peptide derived from MUC-1, an hormonally-regulated protein, is the most widely used serum marker of breast cancer. CA15-3 level increases at the metastatic phase in 50-80% breast cancer patients. Although rise of CA15-3 precede symptoms of metastasis by a mean time of 2-9 months, current international guidelines do not recommend its routine use for screening for metastases because of moderate sensitivity and absence of clinical impact.

Interleukin-2 before antiretroviral therapy in patients with HIV infection: a randomized trial (ANRS 119).

Background: Interleukin (IL)-2 increases CD4 T cell counts when combined with antiretroviral therapy (ART). Whether IL-2 alone can increase CD4 cell counts is unknown.

Methods: A total of 130 adults who had a CD4 cell count of 300-500 cells/microL (and, thus, were not eligible to receive ART) were randomized to receive either intermittent IL-2 therapy or no treatment.

Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.

Several defense mechanisms have been developed and maintained during the evolution to protect human cells against damage produced from exogenous or endogenous sources. We examined the associations between bladder cancer and a panel of 652 polymorphisms from 85 genes involved in maintenance of genetic stability [base excision repair, nucleotide excision repair, double-strand break repair (DSBR) and mismatch repair, as well as DNA synthesis and cell cycle regulation pathways] in 201 incident bladder cancer cases and 326 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model.

Variants in DNA double-strand break repair and DNA damage-response genes and susceptibility to lung and head and neck cancers.

Cigarette smoking is the major risk factor for lung cancer, and together with alcohol for head and neck (H--N) cancer. These genotoxics produced DNA damage and particularly double-strand breaks (DSB) that are removed by various repair pathways. To understand the initiation of these cancers, we performed a genotype analysis to correlate some variants in specific genes in a case-control study of lung and H-N cancers.

"Natural history" of complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Background: Combining complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a new approach allowing curatively intended treatment of multiple malignant peritoneal tumour seedings. This aggressive treatment is frequently followed by a complicated or an unusual postoperative course, that has yet to be described.

Aim: To describe the clinical and biological post-therapeutic course of patients treated with CCRS plus HIPEC, who were considered uncomplicated cases, and were discharged from hospital before the 15th postoperative day.

[Gene expression profiling in cancer research].

Gene expression profiling is increasingly used in cancer research. For each patient, the expression of thousands of genes in the tumour can be measured simultaneously on a microarray. Microarray studies aim at classifying patients based on two types of classification schemes: unsupervised classification, which uses clustering in order to identify homogeneous subtypes of a disease on the basis of gene expression, or supervised classification, which principally aims at the identification of genes or set of genes differentially expressed between tumours with different characteristics (molecular signature), for instance between a group of patients with bad and good prognosis.

Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer.

Background: AKT phosphorylation is a critical step in the activation of growth factor receptors and can mediate tumor resistance to anthracyclines. We evaluated the expression patterns and predictive value of phosphorylated AKT (pAKT) in breast cancer tissues.

Patients And Methods: pAKT expression was assessed by immunohistochemistry in 823 tumors from patients with early breast cancer enrolled in two randomized trials.

Breast cancer molecular subclassification and estrogen receptor expression to predict efficacy of adjuvant anthracyclines-based chemotherapy: a biomarker study from two randomized trials.

Background: The purpose of this study was to determine the predictive value of breast cancer molecular subclassification regarding the benefit of adjuvant anthracycline-based chemotherapy.

Patients And Methods: Tumor samples from 823 patients included in two randomized trials that compared an anthracycline-based chemotherapy with no treatment were used to construct a tissue array. Estrogen receptor (ER), Her2, epidermal growth factor receptor, cytokeratine 5/6 expressions were determined by immunohistochemistry (IHC).