PURPOSE Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. PATIENTS AND METHODS Eligible patients were those with operable, node-positive—or node negative with tumor 1 cm or greater—TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. RESULTS Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = .136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = .0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = .0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. CONCLUSION This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation.

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A comparison of toluene and ethanol (EtOH) induced changes in central nervous system (CNS) function and symptoms were evaluated in two studies, and when possible the effects of toluene were expressed in EtOH equivalent units. The toluene concentrations were 0, 75, and 150 ppm, bracketing the American Conference of Governmental Industrial Hygienists threshold limit value (ACGIH TLV) of 100 ppm. The socially relevant EtOH doses were 0-00, 0 33, and 0-66g EtOH/kg body weight, equivalent to two and four 3 5% 12 ounce beers. Forty two paid college students were used in each study. In the first study, subjects were exposed to toluene and an odour masking agent menthol (0-078 ppm) for seven hours over three days. In the second study EtOH or a placebo was administered at 1530 across three days also in the presence of menthol. Verbal and visual short term memory (Sternberg, digit span, Benton, pattern memory), perception (pattern recognition), psychomotor skill (simple reaction time, continuous performance, symboldigit, hand-eye coordination, finger tapping, and critical tracking), manual dexterity (one hole), mood (profile on mood scales (POMS), fatigue (fatigue checklist), and verbal ability were evaluated at 0800, 1200, and 1600. Voluntary symptoms and observations of sleep were collected daily. A 3 x 3 latin square design evaluated solvent effects simultaneously controlling for learning and dose sequence. An analysis of variance and test for trend were performed on am-pm differences reflecting an eight hour workday and on pm scores for each solvent, in which subjects were their own control. Intersubject variation in absorbance was monitored in breath. A 5 to 10% decrement was considered meaningful if consistent with a linear trend at p < 0-05. At 150 ppm toluene, British Journal of Industrial Medicine 1991;48:750-761 losses in performance were 6-0% for digit span, 12 1% for pattern recognition (latency), 5% for pattern memory (number correct), 6-5% for one hole, and 3% for critical tracking. The number of headaches and eye irritation also increased in a dose-response manner. The greatest effect was found for an increasing number ofobservations ofsleep. A range of2 to 7% decrements suggest the ACGIH TLV of 100 ppm toluene may be a good estimate of the biological threshold supporting a re-evaluation ofthe TLV. At 0-66g EtOH/kg body weight symptoms and performance decrements were 6-6% for digit span, 9-2% for pattern recognition, 4 0% for continuous performance, 7-9% for symbol-digit, 16-5% for finger tapping, 6-2% for critical tracking, and 5-2% for the one hole test. The EtOH equivalents at 150 ppm toluene for digit span (0-56g EtOHlkg/body weight), the latency for pattern recognition (0-66 g EtOH kg body weight), and the one hole element "move" (0-37 g EtOH kg body weight) show that the first two xneasures would be affected at or above the 50 mg% blood alcohol concentration. This concentration is recognised as the lowest alcohol concentration associated with increased numbers of automobile accidents. The r...

An acute inhalation chamber study of 42 college students was performed to investigate the relation between exposure to 0, 75, and 150 ppm of toluene and changes in central nervous system function and symptoms. Paid subjects were exposed for seven hours over three days. Verbal and visual short term memory (Steinberg, digit span, Benton, pattern memory); perception (pattern recognition); psychomotor skill (simple reaction time, continuous performance, digit symbol, handeye coordination, finger tapping, and critical tracking); manual dexterity (one hole); mood (profile of mood scales (POMS)); fatigue (fatigue checklist); and verbal ability were evaluated at 0800, 1200, and 1600 hours. Voluntary symptoms and observations of sleep were collected daily. An analysis of variance and test for trend was performed on the difference and score for each concentration reflecting an eight hour workday where each subject was their own control. A 3 x 3 Latin square study design evaluated toluene effects simultaneously, controlling for learning across the three days and the solvent order. Intersubject variation in solvent uptake was monitored in breath and urine. A 5-10% decrement in performance was considered significant ifit was consistent with a linear trend at p < 0 05. Adverse performance at 150 ppm toluene was found at 6-0% for digit span, 12-1% for pattern recognition (latency), 5-0% for pattern memory (number correct), 6-5% for one hole, and 3 0% for critical tracking. The number of headaches and eye irritation also increased in a dose response manner. The greatest effect was found for an increasing number of observations of sleep. Overall, no clear pattern of neurobehavioural effects was found consistent with the type 1 central nervous system as classified by the World Health Organisation. Subtle acute effects, however, were found just below and above the ACGIH TLV of 100 ppm toluene, supporting the position that the guideline be lowered since the biological threshold ofbehavioural effects may be comparable with the TLV.The acute behavioural effects of inhaling toluene after a single exposure are reversible,' but although reversible, they may also be an early sign of central nervous system (CNS) impairment leading to irreversible losses in performance with repeated exposures.23 Acute decrements may be large enough to decrease the safety margin of industrial tasks or to lower productivity. Evidence from solvent studies suggests that symptoms might occur before other measurable acute CNS effects are apparent."The effects of toluene were first studied under controlled eight hour exposures in 1942.4 Mild CNS symptoms and irritation were reported at 200 ppm, fatigue and muscular weakness were noted at 300 ppm, and headache, dizziness, and staggering were incapacitating at 600 ppm. Mild physiological effects have also been reported at 200 ppm.78Later studies emphasised detecting changes in The evidence suggests that inhaling toluene at 100 ppm over seven hours can cause slight impairments in vigilance, manual dexterity...

Most breast tumors depend on female sex hormones for development and growth, thus being amenable to endocrine therapies. In the management of estrogen receptor (ER)-positive, advanced breast cancer, conventional wisdom dictates the use of endocrine therapy for patients with good prognostic features, whereas chemotherapy is recommended for the treatment of visceral crisis. There is, however, considerable uncertainty regarding the best initial strategy for patients with poor prognostic features other than visceral crisis, such as small-volume visceral involvement and a short disease-free interval after adjuvant therapy. In this article, we examine the role of chemotherapy in ER-positive, advanced breast cancer. Our review of the literature suggests that, in the absence of visceral crisis, endocrine agents should always be considered a major option for the initial treatment of ER-positive, metastatic breast cancer due to their proven efficacy and favorable toxicity profile. Although certain chemotherapy agents can induce higher response rates and more rapid responses, which are desirable effects in particular situations, the up-front use of chemotherapy does not seem to influence the overall outcome of the disease. In the subset of patients with epidermal growth factor type 2-positive disease, on the other hand, current data still do not support the use of endocrine agents alone.