Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population.

Purpose: To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression.

Methods: We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression.

Estimated Life-Years Saved in Women with HER2-Positive Metastatic Breast Cancer Receiving First-Line Trastuzumab and Pertuzumab in the United States.

Background: HER2 positive (HER2+) metastatic breast cancer (MBC) is associated with high mortality. Trastuzumab was approved for use in 1998, but the life-years saved from first-line use are unknown, as are the potential US population benefits from adding pertuzumab.

Objectives: The first aim was to estimate the number of life-years saved by using first-line trastuzumab between 1999 and 2013 in HER2+ women with MBC.

The Lifetime Economic Burden of Inaccurate HER2 Testing: Estimating the Costs of False-Positive and False-Negative HER2 Test Results in US Patients with Early-Stage Breast Cancer.

Background: Patients with breast cancer whose tumors test positive for human epidermal growth factor receptor 2 (HER2) are treated with HER2-targeted therapies such as trastuzumab, but limitations with HER2 testing may lead to false-positive (FP) or false-negative (FN) results.

Objectives: To develop a US-level model to estimate the effect of tumor misclassification on health care costs and patient quality-adjusted life-years (QALYs).

Methods: Decision analysis was used to estimate the number of patients with early-stage breast cancer (EBC) whose HER2 status was misclassified in 2012.

Investigation of adverse-event-related costs for patients with metastatic breast cancer in a real-world setting.

Background: Existing treatments for metastatic breast cancer (mBC) are often effective but can cause adverse events (AEs). This study aimed to identify AEs associated with chemotherapies commonly used in mBC treatment (phase 1) and to quantify the economic impact of these AEs (phase 2).

Materials And Methods: Patients in phase 1 had at least one claim for therapy for mBC, with at least one episode with single or multiple agents.

Comparison of treatment patterns and economic outcomes in metastatic breast cancer patients initiated on trastuzumab versus lapatinib: a retrospective analysis.

Few studies have compared treatment patterns, healthcare resource utilization (HRU), and costs in patients with metastatic breast cancer (mBC) receiving HER2 directed therapy. This study evaluated these outcomes in patients receiving trastuzumab or lapatinib. Adult women with mBC, who were initiated on trastuzumab or lapatinib, on or after March 13, 2007, were selected from the US-based PharMetrics® Integrated Database (2000-2011).

Assessing the discordance rate between local and central HER2 testing in women with locally determined HER2-negative breast cancer.

Background: The importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in invasive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options.

Methods: Breast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared.

Identification and cost of adverse events in metastatic breast cancer in taxane and capecitabine based regimens.

Purpose: We sought to compare the economic impact of treatment-related adverse events (AEs) in patients with metastatic breast cancer (mBC) using taxane- or capecitabine-based treatment regimens as either first- or second-line (FL or SL) therapy in the US.

Methods: We used healthcare claims data from the Truven Health Analytics MarketScan® Commercial Databases to conduct a retrospective cohort study comparing the economic impact of AEs amongst taxane- and capecitabine-treated mBC patients in the US. We selected women diagnosed with mBC between 2008-2010 who received a taxane or capecitabine as first- or second-line (FL or SL) chemotherapy.

Health care utilization and costs by site of service for nonmetastatic breast cancer patients treated with trastuzumab.

Background: Adjuvant trastuzumab treatment is administered to early stage breast cancer patients in physician office (POV) or hospital outpatient (HOP) settings.

Objective: To identify treatment patterns, utilization, and costs by site of care (POV vs. HOP) of patients with adjuvant treatment of breast cancer with trastuzumab.

Bevacizumab confers additional advantage to the combination of trastuzumab plus pertuzumab in trastuzumab‑refractory breast cancer model.

Purpose: We investigated antitumor activity of trastuzumab (T)/T-DM1 + pertuzumab (P) + bevacizumab (B) in T-sensitive (BT474) and T-resistant (BT474HerR) BC models in order to test whether or not the addition of an anti-angiogenic drug can provide a supplementary advantage to the antitumor activity of double HER2–mAB combination.

Methods: In addition to the antitumor activity (xenograft model), we tested antiproliferative effect, and HER2-mediated signals of different antibodies (T or P or T-DM1) in HER2-amplified T-sensitive, T-resistant and HER2-amplified/PIK3CA mutated (HCC1954) BT cell lines by 3D ON-TOP clonogenic growth assay and Western blots.

Results: Data show (1) T, T-DM1 or P blocked p-AKT (>60 %), p-ERK (>50 %) following heregulin in only T-sensitive cells, (2) T/T-DM1 + P, T/T-DM1 + B, and P + B reduced tumor growth as compared to any single-agent treatment, (3) T + P + B achieved almost complete regression of tumor growth, decreased cell proliferation, and inhibited tumor-induced angiogenesis, in both models, (4) antitumor activity of T + P + B was associated with the pharmacodynamic knockdown of p-AKT, and (5) T-DM1 + P caused complete regression of tumor volume in both models.

Assessing the potential cost-effectiveness of retesting IHC0, IHC1+, or FISH-negative early stage breast cancer patients for HER2 status.

Background: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests are commonly used to assess human epidermal growth factor 2 (HER2) status of tumors in patients with breast cancer. This analysis evaluates the likely cost-effectiveness of expanded retesting to assess HER2 tumor status in women with early stage breast cancer.

Methods: We developed a decision-analytic model to estimate the incremental cost-effectiveness ratio (ICER) of expanded reflex testing from a US payer perspective.

Effect of central nervous system metastases on treatment discontinuation and survival in older women receiving trastuzumab for metastatic breast cancer.

Background. Trastuzumab improves survival in HER2-positive women with metastatic breast cancer (MBC). The consequences of longer survival include a higher likelihood of additional metastases, including those in the central nervous system (CNS).

Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab.

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane.

Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER.

Purpose: registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients.

Experimental Design: Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated.

Estimating recurrences prevented from using trastuzumab in HER-2/neu-positive adjuvant breast cancer in the United States.

Background: Breast cancer recurrence is associated with significant morbidity, mortality, and cost. Patients with early stage HER2+ tumors are at increased risk of recurrence. The use of trastuzumab for these patients has been shown to reduce recurrences and improve overall survival.

Effect of trastuzumab on health-related quality of life in patients with HER2-positive metastatic breast cancer: data from three clinical trials.

Background: Trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA) provides clinical benefit when combined with chemotherapy or as monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Given the demonstrated improvement in standard outcomes, it is important to assess this therapy's effect on patients' health-related quality of life (HRQOL).

Effectiveness of superselective chemoembolization and radiofrequency ablation of hepatocellular carcinoma assessed in 21 explanted livers.

The efficacy of superselective transcatheter chemoembolization (TACE) and chemoembolization taking advantage of pharmacologic (noradrenaline) flow manipulation was assessed on 21 explanted livers with hepatocellular carcinoma (HCC). There was a high concentration of chemoembolizate in the target area. Correlation of gross anatomical and immunohistochemical findings (gold standard) of tumor volume, necrosis and residual viable tumor to predicted results by multiphasic helical computed tomography (CT) was poor.

Aminocaproic-acid seal to reduce or prevent bleeding after liver biopsy.

This study investigates the efficacy of an aminocaproic-acid seal to prevent or reduce the risk of bleeding attendant to liver biopsies. The simple technique of occluding the biopsy tract by injecting 1-2 mL of aminocaproic acid, a fibrinolysis inhibitor, while withdrawing the biopsy sheath appears to reduce substantially the risk of delayed bleeding. The technique may be most useful if large core biopsy needles must be used to provide an adequate specimen.

Identification of proteases employed by dendritic cells in the processing of protein purified derivative (PPD).

Dendritic cells (DC) are known to present exogenous protein Ag effectively to T cells. In this study we sought to identify the proteases that DC employ during antigen processing. The murine epidermal-derived DC line Xs52, when pulsed with PPD, optimally activated the PPD-reactive Th1 clone LNC.