Erika P Hamilton

Duke University Medical Center | DUMC · Division of Medical Oncology

Triple negative breast cancer (TNBC) represents a particularly aggressive and difficult to treat form of breast cancer. No specific genetic alterations have been described as characteristic of the disease, with the exception of association with BRCA1/2, EGFR, and KRAS mutations. In this study, we sought to define clinically actionable mutations in...

Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated...

Triple negative metastatic breast cancer can be difficult to treat with primarily cytotoxic options. Nab-paclitaxel has demonstrated improved PFS and tolerability compared with standard cremophor-solubilized paclitaxel; based on this, we examined the efficacy and safety of combining weekly nab-paclitaxel with carboplatin and bevacizumab in TNMBC. I...

This study evaluated self-reported knowledge, practice, and attitudes toward commercially available cytochrome P450 2D6 (CYP2D6) pharmacogenomic testing for patients on tamoxifen for breast cancer (CYPT) among US oncologists while evidence for the use of the test was evolving. A self-administered survey of medical oncology breast cancer specialists...

Correlative science (CS) can potentially augment clinical trial results by identifying biomarkers of response and resistance to a novel intervention. We evaluated recently published breast cancer phase II trials (BP2T) to determine prevalence, characteristics, and outcomes of CS. Through Pubmed, we identified BP2T of systemic therapy published betw...

Sustained HER2 signaling at the cell surface is an oncogenic mechanism in a significant proportion of breast cancers. While clinically effective therapies targeting HER2 such as mAbs and tyrosine kinase inhibitors exist, tumors overexpressing HER2 eventually progress despite treatment. Thus, abrogation of persistent HER2 expression at the plasma me...

Figure S4 showing inhibition of HER2-VIA-induced HER2 ubiquitination by lapatinib. SK-BR-3 cells were pretreated with the proteasome inhibitor MG132 (10 µM) and lapatinib for 30 minutes before HER2-VIA application for 2 hours. After the indicated treatment, cells were lysed and HER2 was precipitated using anti-HER2 rabbit antibody 29D8. Precipitate...

Figure S5 showing the effect of human HER2-specific antibodies on HER2 tyrosine 877 phosphorylation. SK-BR-3 cells were stimulated for 1 hour with the indicated sera from either patients or mice. Protein samples were immunoblotted with anti-HER2 PY877 antibodies (upper panel) or anti-HER2 antibodies (lower panel).

Figure S3 showing sucrose inhibits HER2-VIA-induced internalization of HER2. SK-BR-3 cells were treated with 20 µl HER2-VIA and then incubated with FITC 488-conjugated goat anti-mouse antibody on ice. The cells were then exposed to the following conditions and were then imaged by confocal microscopy: (a) incubation on ice for 1 hour; (b) incubation...

Background Zoledronic acid (ZA) in combination with endocrine therapy (ET) and ovarian ablation (OA) reported a DFS advantage in premenopausal women with early stage breast cancer (EBC) in ABCSG-12. Emerging evidence from pre-clinical studies suggests that ZA increases gamma/delta T-cells (GDT), an immune cell population with anti-tumor activity. T...

Patients with HER2-overexpressing metastatic breast cancer, despite initially benefiting from the monoclonal antibody trastuzumab and the EGFR/HER2 tyrosine kinase inhibitor lapatinib, will eventually have progressive disease. HER2-based vaccines induce polyclonal antibody responses against HER2 that demonstrate enhanced anti-tumor activity when co...

Figure S1 showing flow cytometric assessment of the relative HER2-VIA and trastuzumab binding intensity to HER2-positive SK-BR-3 human breast tumor cells. SK-BR-3 cells were incubated with the indicated dilution of (A) HER2-VIA (1:100 to 1:102,400) or (B) trastuzumab (20 to 0.02 μg/ml) and then stained with the appropriate phycoerythrin-conjugated...

Figure S1. Reduced phosphorylation of AKT following dHER ASCI immunization.

Activation status of the phosphatidylinositol 3-kinase (PI3K) pathway in breast cancer brain metastases (BCBMs) is largely unknown. We examined expression of phospho(p)-AKT, p-S6, and phosphatase and tensin homologue (PTEN) in BCBMs and their implications for overall survival (OS) and survival after BCBMs. Secondary analyses included PI3K pathway a...

A small subset of T cells (gamma-delta T cells) is able to recognize phosphoantigens that are overexpressed in some cancer cells and may selectively target and kill cancer cells with high levels of phosphoantigen. Moreover, nitrogen-containing bisphosphonates, such as zoledronic acid, are able to induce accumulation of specific phosphoantigens in s...

A phase II study of dasatinib, an inhibitor of multiple oncogenic tyrosine kinases including Src, was conducted to evaluate 16-week progression-free rate and tolerability in patients with previously treated metastatic breast cancer (MBC). Real-time assessment of potential tissue biomarkers of Src inhibition was used to optimize dosing. Eligibility...

Five randomized phase III trials - AVF2119g, E2100, AVADO, RIBBON-1, and RIBBON-2 - have reported data on the efficacy and safety of bevacizumab, combined with a variety of chemotherapy agents and in various settings, in patients with metastatic breast cancer (MBC). The E2100 trial demonstrated a significant improvement in progression-free survival...

Investigational cancer therapies may be available outside trials as "off-protocol therapy" (OPRx), with implications for patient safety, trial accrual, and access to care. We conducted a literature-based analysis of recent randomized trials to evaluate the potential scope and impact of OPRx in the United States. A MEDLINE search identified all Engl...

BACKGROUND: This study evaluated self-reported knowledge, practice, and attitudes toward commercially available cytochrome P450 2D6 (CYP2D6) pharmacogenomic testing for patients on tamoxifen for breast cancer (CYPT) among US oncologists while evidence for the use of the test was evolving. METHODS: A self-administered survey of medical oncology brea...

There are now several efficacious treatments for early-stage hormone-receptor-positive breast cancer. Although tamoxifen reduces disease recurrence and death from breast cancer and previously was the standard of care for decades, third-generation aromatase inhibitors (AIs) are now the treatment of choice for postmenopausal women with early-stage br...