Selecting postoperative adjuvant systemic therapy for early-stage breast cancer: An updated assessment and systematic review of leading commercially available gene expression assays.

Gene expression assays (GEAs) can guide treatment for early-stage breast cancer. Several large prospective randomized clinical trials, and numerous additional studies, now provide new information for selecting an appropriate GEA. This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®).

Management of melanoma: can we use gene expression profiling to help guide treatment and surveillance?

Although the incidence of cutaneous melanoma (CM) has been increasing annually, the mortality rate has been decreasing, likely due to better prevention, earlier detection, improved surveillance, and the development of new therapies. Current clinical management guidelines by the National Comprehensive Cancer Network (NCCN) are based on patient risk assignment using staging criteria established by the American Joint Committee on Cancer (AJCC). However, some patients with localized disease (stage I-II), generally considered to have a good prognosis, will develop metastatic disease and die, whereas some patients with later stage disease (stage III-IV) will be cured by surgery, adjuvant therapy, and/or systemic therapy.

Integrating 31-Gene Expression Profiling With Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction.

Unlabelled: National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time.

Clinical Considerations for Integrating Gene Expression Profiling into Cutaneous Squamous Cell Carcinoma Management.

Gene expression profile (GEP) testing is now commercially available for metastatic risk prediction in patients with cutaneous squamous cell carcinoma (CSCC) and one or more high-risk factors. The purpose of this article is to provide an early framework for healthcare providers looking to integrate patient-specific tumor biology into their clinical practice using GEP testing. To develop a framework for clinical use, an expert panel was convened to identify CSCC management decision points where GEP testing may be immediately incorporated into practice until the definitive results of prospective trials become available.

Integrating the melanoma 31-gene expression profile test with surgical oncology practice within national guideline and staging recommendations.

Define changes in clinical management resulting from the use of the prognostic 31-gene expression profile (31-GEP) test for cutaneous melanoma in a surgical oncology practice. Management plans for 112 consecutively tested patients with stage I-III melanoma were evaluated for duration and number of clinical visits, blood work and imaging. 31-GEP high-risk (class 2; n = 46) patients received increased management compared with low-risk (class 1; n = 66) patients.

A path to improve colorectal cancer screening outcomes: faculty roundtable evaluation of cost-effectiveness and utility.

The American Journal of Managed Care® and Exact Sciences Corporation hosted a roundtable meeting to discuss the impact of colorectal cancer (CRC) screening modalities on improving patient outcomes. The roundtable participants were a diverse panel of experts, including primary care, gastroenterology, and oncology providers; experts in health outcomes research and health policy; and managed care executives with commercial and public payer experience. Participants discussed CRC prevention and treatment strategies, screening modalities and adherence, molecular diagnostics, patient navigation, evaluation of large data sets, managed care, outcomes research, quality improvement, and reimbursement policies.

Merkel cell carcinoma: long-term follow-up of a single institution series and clinical outcomes by immunological status.

Merkel cell carcinoma (MCC) usually arises in sun-exposed areas of older patients and might be more aggressive in the immunocompromised. We performed a retrospective chart review of 40 consecutive MCC patients treated at our institution between the years 2006-2017. Clinical and epidemiologic data were utilized and therapy and survival were analyzed.

Identification of risk in cutaneous melanoma patients: Prognostic and predictive markers.

New therapeutic modalities for melanoma promise benefit in selected individuals. Efficacy appears greater in patients with lower tumor burden, suggesting an important role for risk-stratified surveillance. Robust predictive markers might permit optimization of agent to patient, while low-risk prognostic markers might guide more conservative management.

Inferior outcomes in immunocompromised Merkel cell carcinoma patients: Can they be overcome by the use of PD1/PDL1 inhibitors?

Cases of Merkel cell carcinoma have become increasingly more common in the last two decades, and its incidence has been predicted to climb further. Immunosenescence might explain in part the higher Merkel cell carcinoma prevalence in seniors aged 70 and older. This cancer might also be more aggressive in immunocompromised patients.

Adenocarcinoma of the appendix occurring in a patient treated with paclitaxel for locally advanced esophageal cancer.

Paclitaxel has been linked with a number of immunosuppressive effects such as decreased numbers and activity of dendritic cells, NK-cells and monocytes, which may in turn lead to defective T-cell activation. In addition, this agent was shown to cause mitotic arrest resembling high-grade dysplasia throughout the gastrointestinal tract, including the appendix. We have previously documented a series of lung cancer patients who developed pre-malignant colonic polyps and/or colon cancer either during or weeks following chemotherapy with paclitaxel, suggesting a potential role of this agent in their pathogenesis.

Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays.

Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision-making. This review details the development and validation of six multi-gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use.

Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized Phase II study.

Hormone receptor-positive breast cancer is treated with estrogen inhibitors. Fulvestrant (FASLODEX™), an estrogen receptor (ER) antagonist with no known agonist effects, competitively binds, blocks and degrades the ER. Vascular endothelial growth factor (VEGF) may mediate resistance to ER antagonists.

A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma.

Background: Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab.

Methods: In this randomized, double-blind, phase II biomarker study (ClinicalTrials.

Understanding tumor profiling and assessing treatment.

Gene expression profiling allows us to look into a tumor cell to see how genetic information is communicated and affects cell behavior. Data gathered during the development of the 70-gene assay (MammaPrint) set the stage for future assay development. Recently, a 21-gene assay (Oncotype DX) was recommended by ASCO and NCCN as a standard of care for newly diagnosed, stage 1 or 2, node-negative, estrogen-receptor-positive breast cancer patients.

Breast cancer chemoprevention phase I evaluation of biomarker modulation by arzoxifene, a third generation selective estrogen receptor modulator.

Purpose: Arzoxifene, a new selective estrogen receptor modulator with strong breast antiestrogen activity and absence of uterine agonist activity, was explored as a potential chemoprevention agent. We performed a multi-institutional evaluation of arzoxifene in women with newly diagnosed ductal carcinoma in situ or T1/T2 invasive cancer.

Experimental Design: In a Phase IA trial, 50 pre- or postmenopausal women were randomized to 10, 20, or 50 mg of arzoxifene daily in the interval between biopsy and re-excision or were enrolled as no-treatment controls.