Paula T. Rieger

Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk.

PURPOSE Previous studies of mutations in BRCA1 or BRCA2 have used detection methods that may underestimate the actual frequency of mutations and have analyzed women using heterogeneous criteria for risk of hereditary cancer. PATIENTS AND METHODS A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one first- or second-degree relative with either diagnosis underwent sequence analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was discovered in BRCA1). Results were correlated with personal and family history of malignancy. RESULTS Deleterious mutations were identified in 94 (39%) women, including 59 of 117 (50%) from families with ovarian cancer and 35 of 121 (29%) from families without ovarian cancer. Mutations were identified in 14 of 70 (20%) women with just one other relative who developed breast cancer before age 50. In women with breast cancer, mutations in BRCA1 and BRCA2 were associated with a 10-fold increased risk of subsequent ovarian carcinoma (P = .005). CONCLUSION Because mutations in BRCA1 and BRCA2 in women with breast cancer are associated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data.

Phase Ia/Ib trial of anti-GD2 chimeric monoclonal antibody 14.18 (ch14.18) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in metastatic melanoma

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral nerve dysesthesias, myalgias, and weakness. Dose-limiting toxicity was observed at 60 mg/m2 and consisted of severe hypertension, hypotension, and atrial fibrillation in one patient each, respectively. Significant increases in white blood cell count, granulocyte count, eosinophil count, and monocyte count occurred after rhGM-CSF treatment. Significant enhancement of in vitro and in vivo monocyte and neutrophil tumoricidal activity and antibody-dependent cellular cytotoxicity along with significant elevations in C-reactive protein and neopterin were observed. Despite these immunological and biological changes, no antitumor activity was seen. In short, the combination of ch14.18 and rhGM-CSF resulted in toxicity similar to that observed with ch14.18 alone without improvement in tumor response.

Assessment and epidemiologic issues related to fatigue

At The University of Texas M. D. Anderson Cancer Center, a multidisciplinary workgroup was assembled to review issues, current research, and areas of future research related to the assessment and epidemiology of cancer‐related fatigue. Interactive discussion facilitated by a moderator determined the major areas of focus for future research in this arena. The groups ideas were presented to the entire conference following the session. Several gaps in current research related to the assessment and epidemiology of cancer‐related fatigue were identified. Cancer 2001;92:1733–1736.

Phase II radioimmunotherapy trial with131I-CC49 in colorectal cancer

Background. Radiolabeled CC49, a second generation high affinity monoclonal antibody (MoAb) reactive with tumor‐associated glycoprotein 72 (TAG72) has undergone previous Phase I testing in patients with colon cancer. Based on this report, the authors treated 15 refractory metastatic colon cancer patients with 131I‐CC49 to determine its overall toxicity and the response to therapy of patients treated with it.

Genetic testing and informed consent.

OBJECTIVES To discuss unique issues related to cancer predisposition genetic testing and informed consent. DATA SOURCES Published professional articles, review articles, research articles, clinical practice, position statements, websites, and textbooks. CONCLUSIONS The discovery of germline mutations that confer a predisposition for the development of cancer will continue. The provision of adequate information is central to the process of genetic counseling and testing so that individuals may give informed consent and make choices appropriate to their own specific circumstances. IMPLICATIONS FOR NURSING PRACTICE The use of genetic information for the management of cancer will impact the practice of all oncology nurses in the coming years. Knowledge of genes that predispose for cancer and standards that delineate essential components of quality care during the informed consent process is vital.

Future projections in biotherapy

OBJECTIVES To review barriers to effective biotherapy and future trends in biotherapy and the expertise needed by oncology nurses to address the challenges that will result from these changes. DATA SOURCES Review articles and book chapters related to biotherapy. CONCLUSIONS To sustain the progress made in biotherapy, barriers that limit the effectiveness of treatment must be addressed and basic research continued. Targeted areas for new biotherapy strategies are interference with cellular communication, control of the cell cycle, and interference with the process of metastasis. IMPLICATIONS FOR NURSING PRACTICE Nurses with creativity and motivation will continue to lead the way in developing management strategies for patients receiving future therapies.