Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype

Background

Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer.

Methods

Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method.

Results

Of 132 MBC patients, those with heterologous mesenchymal MBC (n?=?45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78–0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32–0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6–3.3; p?<?0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response.

Conclusions

Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC’s unique biology.

     

Quality assurance management methods applied to a local-level primary health care system in rural Nigeria

Introduction. Management of primary health care (PHC) systems in less developed countries is often impeded by factors such as poorly trained personnel, limited financial resources, and poor worker morale. This study explored the ability of local-level PHC supervisors in rural Nigeria to use quality assurance (QA) management methods to improve the quality of the PHC system. Methods. PHC supervisors from Bama Local Government Area were trained for 3 days in the use of QA methods and tools. The supervisors targeted the supervisory system and the health information system (HIS) for improvement. Health worker performance in diarrhoea case management was assessed, using a simulated case, to measure the impact of supervision. A HIS audit assessed data collection forms used by 17 PHC facilities. Gaps in quality were monitored over a 2-month study period and flaws in work processes were modified. Results. PHC supervisors introduced a checklist during monthly visits to facilities to monitor how workers managed cases of diarrhoea. Performance in history-taking, physical examination, disease classification, treatment and counselling improved over the evaluation period. The HIS audit found that a variety of reporting forms were used at PHC facilities. After HIS reporting was standardized, the number of health facilities using a daily disease registry significantly improved during the study period. Conclusions. QA management methods were used by PHC supervisors in Nigeria to improve supervision and the HIS. QA management methods are appropriate for improving the quality of the PHC in Nigeria and in other less developed countries where at least a minimal PHC infrastructure exists.     

Steady state assumptions in DALYs: effect on estimates of HIV impact

OBJECTIVE: The disability adjusted life year (DALY) and the healthy life year (HeaLY) are both composite indicators of disease burden in a population, which combine healthy life lost from mortality and morbidity. The two formulations deal with the onset and course of a disease differently. The purpose of this paper is to compare the DALY and HeaLY formulations as to differences in apparent impact when a disease is not in an epidemiological steady state and to explore the implications of the differing results. DESIGN: HIV is used as a case study of a major disease that is entering its explosive growth phase in large areas of Asia. Data from the global burden of disease study of the World Bank and World Health Organisation for 1990 has been used to compare burden of disease measures in the two formulations. SETTING: The data pertain to global and regional estimates of HIV impact. RESULTS: The DALY attributes life lost from premature mortality to the year of death, while the HeaLY to the year of disease onset. This results in very large differences in estimates of healthy life lost based upon the DALY construct as compared with the HeaLY, for diseases such as HIV or those with a strong secular trend. CONCLUSION: The demonstration of the dramatic difference between the two indicators of disease burden reflects a limitation of the DALY. This information may directly influence decision making based on such methods and is critical to understand.     

Increased CSF F2-isoprostane concentration in probable AD

OBJECTIVE: To quantify F2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls. BACKGROUND: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans. Recently, we showed that F2-isoprostane concentrations are significantly elevated in CSF obtained postmortem from the lateral ventricles of patients with definite AD compared with controls. METHODS: F2-isoprostanes were quantified by gas chromatography/negative ion chemical ionization mass spectrometry. RESULTS: CSF F2-isoprostanes were increased significantly in patients with probable AD, but not in ALS patients, compared with controls. CONCLUSIONS: Increased CSF F2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD.     

Changes in clinical measures of autonomic nervous system function related to cancer chemotherapy-induced nausea

Individual cancer patients differ in their nausea/vomiting response to chemotherapy. It is not known why patients receiving the same chemotherapy have different severity of side effects. Several lines of research implicate the autonomic nervous system (ANS) in the development of chemotherapy-induced nausea. We examined the association between autonomic reactivity and the level of nausea experienced following chemotherapy in 20 patients with ovarian cancer treated with cisplatin or carboplatin who received the same antiemetic. We applied eight common non-invasive clinical tests of autonomic function prior to inpatient chemotherapy treatment, 2 h after treatment and again 24 h following treatment. Two hours after chemotherapy and before any nausea was reported by the patients, the nine patients who subsequently experienced high levels of nausea had a greater overall percentage of abnormal clinical ANS tests than the 11 patients who subsequently developed low levels of nausea (P < 0.01). Twenty-four hours after treatment, the overall number of abnormal autonomic tests remained non-significantly higher than at the pretreatment baseline for the high nausea group. Demographic and clinical characteristics were not related to chemotherapy-induced nausea in this sample. Autonomic reactivity appears to be related to the development of nausea following chemotherapy. Further investigation of ANS involvement in chemotherapy-induced nausea could increase understanding of nausea etiology and potentially lead to the prediction of susceptible patients.     

Generation of antigen specific CD8+ cytotoxic T cells following immunization with soluble protein formulated with novel glycoside adjuvants.

Presentation of peptide on MHC class I molecules is essential to elicit cytolytic T cell (CTL) activity. Such peptides are a result of the cytosolic, or class I, antigen processing pathway. Due to the segregation of the class I and the exogenous processing pathway, soluble protein cannot enter the class I pathway and is thus incapable of inducing CTL. However careful formulation with adjuvants can overcome this obstacle. In this study we evaluated the capacity of two novel amphiphilic adjuvants, better termed delivery vehicles, to elicit CTL activity in a C57Bl/6 murine model with ovalbumin (OVA) as an antigen. Incomplete Freund's adjuvant and aluminium hydroxide (Alhydrogel) were used as reference adjuvants. In addition the oil-in-water emulsion Provax was used throughout as a positive control adjuvant. Both amphiphile preparations were capable of eliciting potent CTL activity after administration of one immunizing dose of ovalbumin. CTL were CD8+ restricted as assessed by in vitro depletion of CD8+ and CD4+ T cells. CTL activity was also MHC-restricted as well as specific for the H-2Kb OVA motif SIINFEKL.     

Laparoscopy in the evaluation of gynecologic cancer.

Laparoscopy was used to evaluate 60 patients with a variety of known or suspected gynecologic neoplasms. Diagnostic laparoscopy was performed on 18 patients to confirm benign or malignant pelvic masses or to confirm peritoneal carcinomatosis. Ten of these 18 patients (56%) were found to have unresectable carcinomatosis or benign disease which did not require further surgery. Staging laparoscopy was performed on 13 patients of which 3 had clinically unsuspected intraperitoneal spread of their disease. Surveillance laparoscopy was performed on 29 patients to determine the remission, regression, or progression of their disease following treatment; 8 (27%) had progressive or unresectable persistent disease. Despite the fact that the study comprised a high-risk group of previously operated on or irradiated patients, there was only one major complication. There was, however, a 10% incidence of laparoscopic failure from inadequate visualization. Twenty-one of the study patients (35%) were spared a laparotomy by the use of laparoscopy. The findings of this investigation help to identify those gynecologic oncology patients who should benefit most from the use of laparoscopy as an adjunct to the diagnosis, staging, or surveillance of intraabdominal malignant tumors.