Jennifer A. Crozier

Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines

Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclines in the adjuvant setting for patients with breast cancer. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.

Vemurafenib: an evidence-based review of its clinical utility in the treatment of metastatic melanoma

The discovery of BRAF mutations in the majority of patients with metastatic melanoma combined with the identification of highly selective BRAF inhibitors have revolutionized the treatment of patients with metastatic melanoma. The first highly specific BRAF inhibitor, vemurafenib, began clinical testing in 2008 and moved towards a rapid approval in 2011. Vemurafenib induced responses in ~50% of patients with metastatic BRAF-mutant melanoma and demonstrated improved overall survival in a randomized Phase III trial. Furthermore, vemurafenib is well-tolerated with a low toxicity profile and rapid onset of action. Finally, vemurafenib is active even in patients with widely metastatic disease. Despite the success of vemurafenib in treating patients with BRAF-mutant metastatic melanoma, most, if not all, patients ultimately develop resistance resulting in disease progression at a median time of ~6 months. Multiple mechanisms of resistance have been described and rationale strategies are underway to combat resistance. This review highlights the development, clinical utility, resistance mechanisms, and future use of vemurafenib both in melanoma and other malignancies. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.

Effect of body mass index on tumor characteristics and disease-free survival in patients from the HER2-positive adjuvant trastuzumab trial N9831

Data suggest that weight, and specifically body mass index (BMI), plays a role in breast cancer development and outcome. The authors hypothesized that there would be a correlation between BMI and clinical outcome in patients with early stage, human epidermal receptor 2 (HER2)‐positive breast cancer enrolled in the N9831 adjuvant trial.

N0436 (Alliance): A Phase II Trial of Irinotecan With Cetuximab in Patients With Metastatic Breast Cancer Previously Exposed to Anthracycline and/or Taxane-Containing Therapy.

BACKGROUND Irinotecan has a 20% to 25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). Epidermal growth factor receptor (EGFR) is overexpressed in some MBC, especially in triple-negative breast cancer (TNBC). Cetuximab is a monoclonal antibody against EGFR with additive preclinical activity with irinotecan. PATIENTS AND METHODS We report a 1-stage phase II study on MBC, measurable disease, and previous anthracycline and/or taxane therapy. Patients received cetuximab 400 mg/m(2) on day 1 cycle 1 then 250 mg/m(2) weekly thereafter and irinotecan 80 mg/m(2) on days 1 and 8 of each 21-day cycle. The primary end point was overall RR (ORR) according to Response Evaluation Criteria in Solid Tumors criteria (version 1.1). RESULTS Of 19 eligible patients enrolled from February to September 2006, 14 patients (74%) had visceral disease, seven patients (37%) were hormone receptor-positive, two patients (11%) HER2-positive, and 11 patients (58%) were triple-negative. Patients received a median of 2 cycles (range, 1-37). Confirmed ORR was 11% (95% confidence interval [CI], 1%-33%), with 1 partial response and 1 complete response. One patient had stable disease for 8 months. RR for TNBC versus non-TNBC was 18% versus 0% (P = .49). Median time to progression was 1.4 months (95% CI, 1.0-2.2) and median overall survival was 9.4 months (95% CI, 2.8-16.1). Twelve patients had disease progression within 2 cycles during therapy. Because of a low RR and rapid disease progression, the study leadership decided to close the trial early. CONCLUSION The tolerability of the combination of cetuximab and irinotecan is acceptable but demonstrated low overall activity. Potentially promising results were noted in patients with TNBC and further studies of these patients might be considered.

Persistent Disparities Among Patients With T-Cell Non-Hodgkin Lymphomas and B-Cell Diffuse Large Cell Lymphomas Over 40 Years: A SEER Database Review.

BACKGROUND As of 2013, more than 550,000 people are living with non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS We undertook a large Surveillance Epidemiology and End Results (SEER) based analysis to describe outcome disparities in different subgroups of aggressive T-cell and B-cell NHL patients, with a focus on various ethnicities. RESULTS The final analysis included 7662 patients with T-cell and 84,910 with B-cell NHL. Survival analysis revealed that male sex and increasing age were independent predictors of worse overall survival (OS; P < .001). For aggressive T-cell NHL, there was no significant improvement in median OS between 1973 and 2011 (P = .081), and ethnic minorities (Asians, Hispanics, and African Americans) had significantly worse OS than whites (P < .001). There were similar trends for age, sex, and race for diffuse large B-cell NHL, but a significant improvement in median OS was seen over time (P < .001). CONCLUSION These results are the first to elicit outcomes in a broad classification of ethnic minorities and underscore the urgency for development of novel therapeutics, especially in T-cell NHL. In addition, in-depth studies of disease biology and health care utilization are required for better triage of health care resources, especially for ethnic minorities.

HER2 testing and its predictive utility in anti-HER2 breast cancer therapy

Breast cancer treatment is dependent on accurate pathologic diagnosis. HER2 testing is now universally recommended as part of evaluation of invasive breast cancer. HER2 testing is available via various slide and non-slide based assays, and interpretation of results continues to evolve. Herein we review these testing modalities and their incorporation into the 2013 ASCO/CAP guidelines. Once accurate HER2 status has been established the proper treatment based on recent clinical trials can be instituted.

First Report of Nocardia beijingensis Infection in an Immunocompetent Host in the United States

ABSTRACT Here we describe the first reported case of Nocardia beijingensis infection in the United States, made rarer by its presence in an immunocompetent patient.

Breast cancer brain metastases: Molecular subtype, treatment and survival

BACKGROUND No clear guidelines exist for management of breast cancer brain metastases (BCBM). OBJECTIVE We assessed the relationship between patient and tumor characteristics, treatment, and overall survival (OS). METHODS We conducted a retrospective review of 196 patients who received brain radiation for BCBM between 2009-2013 at Mayo Clinic. Primary tumor characteristics were collected, including simplified molecular subtype. Other characteristics included patients ECOG, number of brain lesions at BCBM diagnosis, and treatment received, including neurosurgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). The primary endpoint was OS from time of BCBM diagnosis. RESULTS Single-variable analysis revealed patients with HER2+ breast cancer had improved OS (HR = 0.6, p = 0.008). Compared to patients with 1-3 brain lesions, the risk of death in patients with leptomeningeal disease was 2.5-fold higher (p = 0.003). Worsening ECOG status was associated with worsening OS. Patients who received SRS and WBRT had improved OS (HR = 0.37, p < 0.001) compared to patients receiving WBRT alone. CONCLUSIONS Patients with the best OS had an ECOG of 0, HER2+ disease, and 1-3 brain lesions. The best OS was associated with the combination of neurosurgery and radiation therapy. A comprehensive treatment plan including neurosurgical evaluation and radiation therapy should be considered for patients with BCBM.

Vancomycin Induced Neutropenia: A Case Report

Vancomycin is a glycopeptide antibiotic with widespread use since 1958. Vancomycin is clinically indicated for the treatment of methicillin-resistant strains of coagulase negative and coagulase positive staphylococcal infections, gram-positive penicillin-resistant infections and as an alternative treatment for penicillin-allergic patients. Vancomycin induced neutropenia is a rare side effect. We present the case of a 23 year old man with recurrent fevers and persistently positive blood cultures growing viridans group streptococci. He was found to have endocarditis requiring aortic valve replacement. Due to the patient’s allergies he was treated with IV vancomycin therapy. This resulted in the uncommon adverse event of vancomycin induced neutropenia. The patient subsequently responded to granulocyte colony stimulating factor. Vancomycin induced neutropenia is an uncommon but serious adverse reaction with the potential for morbidity and mortality. Further guidelines are needed for leukocyte monitoring during vancomycin therapy and the use of granulocyte colony stimulating factor to treat this adverse effect.

Correction: Folate receptor-α (FOLR1) expression and function in triple negative tumors.

The tenth author’s name is spelled incorrectly. The correct name is: Alvaro Moreno-Aspitia. The Academic Editor field is missing from the published paper. The name of the Academic Editor is: Aamir Ahmad, Wayne State University School of Medicine, United States.