Care of Seniors with Breast Cancer - Treatment Received and Refining Decision Making.

AIMS: Treatment decisions for older patients with breast cancer are complex and evidence is largely extrapolated from younger populations. Frailty and comorbidity need to be considered. We studied the baseline characteristics and treatment decisions in older patients in Christchurch with breast cancer and assessed survival outcomes and prognostic/discriminatory performance of several tools. MATERIALS AND METHODS: We searched the Canterbury Breast Cancer Registry and identified patients aged 70 years or older at diagnosis with invasive, non-metastatic breast cancer between 1 June 2009 and 30 June 2015. We retrieved demographics, treatment and outcome information. Overall survival and breast cancer-specific survival were estimated. Tools analysing performance status and comorbidity were assessed for their prognostic and discriminatory power. RESULTS: In total, 440 patients were identified. Primary surgery was carried out for 362 patients (82.3%): breast-conserving surgery in 114 (of whom 88.6% received radiation therapy); mastectomy in 248 (of whom 24.6% received radiation). Hormone therapy was given for 265 (71.1%) patients with oestrogen receptor-positive cancers. Two hundred and seventy-four (62.3%) patients received full standard treatment, which was associated with significantly improved 5-year survival and 5-year breast cancer-specific survival. The median estimated overall survival was 8.2 years (95% confidence interval 7.3-9.1 years). Of those who died, 71.3% of deaths were due to causes other than breast cancer or unknown causes. The comorbidity-adjusted life expectancy (CALE) showed partial prognostic accuracy. CALE, Charlson and Eastern Cooperative Oncology Group tools all showed discriminatory value. CONCLUSION: In this population-based series of older patients with breast cancer, showing high levels of primary and adjuvant treatment, patients were more likely to die of causes other than breast cancer. Performance status and comorbidity tools showed prognostic and discriminatory potential in this population supporting their use in treatment decision making. CALE showed the most potential to improve treatment decisions but requires validation in this population to improve prognostic accuracy.

Smoking habits in a cohort of U.K. adolescents.

Active smoking is an increasing problem amongst U.K. teenagers. The smoking habits of a cohort of 14-16-year-olds were determined and the association between regular active smoking and domestic and social factors investigated. Current smoking habits of a cohort of 2289 14-16-year-olds were assessed using a simple postal questionnaire. Data concerning potential factors associated with active smoking were collected from questionnaire completed by parents. Nine hundred and sixty-nine (44.8%) children admitted to having smoked at some time, with 562 (30.0%) having smoked in the previous 12 months. Three hundred and six (14.1%) children were regular smokers and 158 (51.6% of regular smokers, 7.3% of total cohort) smoked daily. Age, number of other children in the household, parental smoking, smoking sibling(s) and living in a single parent household were all independently associated with regular smoking. Regular smoking was a significant problem amongst this cohort of teenagers. Living with other smokers, age, household size and living with one parent all predicted a regular smoking habit.

The natural history of respiratory symptoms in a cohort of adolescents.

A cohort of 2,289 children, previously studied at the age of 6-8 yr, were followed up by means of a postal questionnaire when aged 14 -16 yr to examine the association between potential risk factors and the natural history of respiratory symptoms. Children with current symptoms, persistent symptoms, and late-onset symptoms were identified and multivariate analyses were performed to determine the independent association between risk factors and these various symptom-based subgroups. Personal and family history of atopy was significantly associated with all symptom groups and with the presence of doctor-diagnosed asthma. Smoking, either active or passive, was shown to be significantly associated with current, persistent, and late-onset symptoms. Other factors shown to be significantly associated with certain symptom groups were gender (late-onset wheeze), single-parent households (current cough, persistent cough), social class (late-onset wheeze), number of children in the household (persistent wheeze, late-onset cough), number of furry pets in the household (current wheeze), birth weight (late-onset wheeze), and gas cookers (current wheeze, persistent wheeze). In a subgroup of children studied in more detail in 1987, bronchial hyperresponsiveness in 1987 was positively associated with persistent wheeze in 1995, whereas positive skin-prick testing in 1987 was not.

Effects of 0.2 ppm ozone on biomarkers of inflammation in bronchoalveolar lavage fluid and bronchial mucosa of healthy subjects.

Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.

Effects of ozone on epithelium and sensory nerves in the bronchial mucosa of healthy humans.

Neuropeptides released from sensory nerves during inflammation have potent effects on bronchomotor tone, airway secretion, and inflammatory cells. We investigated the effects of ozone on sensory nerves by exposing 12 healthy, nonsmoking subjects to 0.2 ppm ozone and filtered air (FA) for 2 h on separate occasions, with intermittent exercise and rest. Spirometry was performed at baseline and 15 min after exposures, and bronchoscopy (bronchial biopsy and bronchoalveolar lavage [BAL]) was done 6 h after exposure. Frozen sections were immunostained for the anatomic neural marker protein gene peptide (PGP) 9.5 and the sensory neutropeptides substance P (SP) and calcitonin-gene-related peptide (CGRP). Nerves in the submucosa were quantified by image analysis. A trend toward an increase in the levels of polymorphonuclear leukocytes (PMNs) (air versus ozone, median [interquartile range]: 3.5 [2 to 5.3%] versus 9.8 [4.2 to 16.3%], p = 0.07) and ciliated epithelial cells (median [interquartile range]: 1.6 [1.3 to 3.4%] versus 5 [2.2 to 9.8%], p = 0.05) was observed in the BAL fluid (BALF). There was a significant decrease in SP immunoreactivity following ozone exposure (median [interquartile range]: 0.6 [0.05 to 1.2] versus 0.15 [0.08 to 0.18], p < 0.05). A significant inverse correlation was observed between SP immunoreactivity and: (1) percent PMNs and ciliated epithelial cells in the BALF; and (2) percent change in FEV1 following exposure to ozone. These findings indicate that short-term exposure to 0.2 ppm ozone causes epithelial shedding and stimulates subepithelial sensory nerves to release SP into the airways. The release of SP could contribute to bronchoconstriction and subsequent neutrophil infiltration into the airways.

Tracheobronchomegaly: an unusual presentation of a rare condition.

Tracheobronchomegaly is a rare cause of recurrent chest infections often with persistent, unproductive cough. A case is described which presented as a severe life threatening pneumonia in which the bronchoscopic, radiographic, and computed tomographic findings are given.