Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer.

This account of the highlights of the eighth St Gallen (Switzerland) meeting in 2003 emphasizes new information that has emerged during the 2 years since the seventh meeting in 2001. This article should be read in conjunction with the report of that earlier meeting. Recommendations for patient care are so critically dependent on assessment of endocrine responsiveness that the importance of high-quality steroid hormone receptor determination and standardized quantitative reporting cannot be overemphasized. The International Consensus Panel modified the risk categories so that only endocrine receptor-absent status was sufficient to reclassify an otherwise low-risk, node-negative disease into the category of average risk. Absence of steroid hormone receptors also was recognized as indicating endocrine nonresponsiveness. Some important areas highlighted at the recent meeting include: (1) recognition of the separate nature of endocrine-nonresponsive breast cancer-both invasive cancers and ductal carcinoma-in-situ; (2) improved understanding of the mechanisms of acquired endocrine resistance, which offer exciting prospects for extending the impact of successful sequential endocrine therapies; (3) presentation of high-quality evidence indicating that chemotherapy and tamoxifen should be used sequentially rather than concurrently; (4) availability of a potential alternative to tamoxifen for treatment of postmenopausal women with endocrine-responsive disease; and (5) the promise of newly defined prognostic and predictive markers.     

Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.

BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.     

Diet Quality Index as a predictor of short-term mortality in the American Cancer Society Cancer Prevention Study II Nutrition Cohort

The Diet Quality Index (DQI) was developed to measure overall dietary patterns and to predict chronic disease risk. This study examined associations between DQI and short-term all-cause, all-circulatory-disease, and all-cancer mortality in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, a cohort of US adults aged 50-79 years enrolled in a prospective study. After 4 years of follow-up (1992-1996), there were 869 deaths among 63,109 women and 1,736 deaths among 52,724 men. All study participants reported being disease free at baseline in 1992-1993. In age-adjusted Cox models, a higher DQI, which was indicative of a poorer quality diet, was positively related to all-cause and all-circulatory-disease mortality rates in both women and men and to cancer mortality in men only. However, in fully adjusted Cox models, only circulatory disease mortality was clearly positively related to DQI and only in women (medium-low-quality diet vs. highest-quality diet: rate ratio = 1.86, 95% confidence interval: 1.19, 2.89). Although trend tests indicated significant positive relations between DQI and all-cause mortality, effects were small (rate ratios 相似文献   

Evaluation of the effectiveness of a community-based enriched model prenatal intervention project in the District of Columbia.

OBJECTIVE: To evaluate an enriched prenatal intervention program designed to reduce the risk of low birth weight. STUDY SETTING: Freestanding community-based prenatal intervention project located in a poor inner-city community, serving mostly African American women. STUDY DESIGN: All women less than 29 weeks pregnant were eligible to participate. They were compared to women who lived in neighborhoods with similar rates of poverty. DATA COLLECTION: The birth certificate was the source of data on maternal age, education, marital status, timing and frequency of prenatal care attendance, parity, gravidity, prior pregnancy terminations, fetal and child deaths, and birth weight. PRINCIPAL FINDINGS: Thirty-eight percent of the women who delivered live-born infants in the study area participated in the program. There were no differences in low- and very low birthweight rates in the study and comparison groups. In a secondary analysis comparing participants and nonparticipants in the study census tracts, participants were at higher risk for low and very low birth weight, and they adhered more closely to the schedule of prenatal visits than nonparticipants. Low- and very low birthweight rates were lower among participants than among nonparticipants and comparison women. CONCLUSION: The Better Babies Project did not have an effect on the overall low- and very low birthweight rates in the study census tracts. This was probably due to the low participation rates and the high population mobility.     

Predominance of nontypeable Haemophilus influenzae in children with otitis media following introduction of a 3+0 pneumococcal conjugate vaccine schedule

In Australia the 7-valent pneumococcal conjugate vaccine (PCV7) is administered at 2, 4 and 6 months of age, with no booster dose. Information on bacterial carriage and the aetiology of recurrent acute otitis media (rAOM) after introduction of PCV7 using the 3 + 0 schedule is required to evaluate the potential impact of second generation pneumococcal vaccines. We found that 2-4 years after introduction of PCV7 in the National Immunisation Program, nontypeable Haemophilus influenzae (NTHi) was the predominant pathogen isolated from the nasopharynx and middle ear of children with a history of rAOM. Compared with healthy controls (n = 81), NTHi and Streptococcus pneumoniae carriage rates were significantly higher in children with a history of rAOM (n = 186) (19% vs. 56% p < 0.0001 and 26% vs. 41%, p = 0.02, respectively). Carriage of PCV7 pneumococcal serotypes was rare, whereas PCV7-related and non-PCV7 serotypes were isolated of 38% of cases and 24% of controls. Serotype 19A was the most common serotype isolated from the nasopharynx and middle ear and accounted for 36% (14/39) of total pneumococcal isolates with reduced susceptibility to cotrimoxazole. Of the 119 children carrying NTHi, 17% of isolates were β-lactamase positive.The scarcity of PCV7 serotypes in children with and without a history of rAOM indicates that the 3 + 0 PCV7 schedule is preventing carriage and rAOM from PCV7 serotypes. Introduction of new vaccines in Australia with increased pneumococcal serotype and pathogen coverage, including 19A and NTHi, should decrease the circulation of antibiotic-resistant bacteria and reduce the burden of rAOM.     

Treatment of adolescent overweight and obesity

Adolescence is a vulnerable period for the development of obesity, and adolescent weight tracks strongly into adulthood. Previous reviews of treatment strategies have failed to discriminate between adolescents and children, thereby, disregarding the uniqueness of this population. Hence, this review aims to summarise the evidence for treatment approaches for adolescent obesity. Pubmed, OVID, EBSCOhost and Google Scholar were searched for randomised controlled trials, meta-analyses and systematic reviews testing treatments for overweight/obese adolescents (aged 12–19 years), published from 1982–2006 in English. Eligible studies had to assess either weight, percentage overweight, body mass index (BMI) or body fat. Thirty-four randomised controlled trials were eligible. The results of this review indicate that the safety and efficacy of surgical and pharmacotherapy treatments for adolescent obesity is uncertain. Diet and physical activity approaches may improve obese status in the short term. However, obesity interventions appear more effective when strategies are combined, rather than when used in isolation. Psychological interventions, such as behavioural and cognitive behavioural therapy, show promise in achieving the necessary lifestyle changes for obesity reduction; however, long-term follow-up studies are needed. There were multiple limitations in appraising the literature. Inconsistent definitions of overweight/obesity make comparisons between studies difficult. Many studies have not used direct adiposity measures, have failed to assess pubertal status or have not used an exclusive adolescent sample. We conclude that, despite these limitations, current evidence indicates that behavioural and cognitive behavioural strategies combined with diet and physical activity approaches may assist in reducing adolescent obesity,although long-term follow-up studies are needed. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Growth factor-induced mobilization of dendritic cells in kidney and liver of rhesus macaques: implications for transplantation

Hematopoietic growth factors (HGF) mobilize potential tolerogenic cells in transplant donors. Fms-like tyrosine kinase 3 ligand (Flt3L) mobilizes stem cells and dendritic cells (DCs) in human and nonhuman primate blood. Blood and renal and liver biopsies were obtained from untreated and Flt3L-mobilized rhesus macaques. Flt3L increased the number of myeloid CD11c(hi) and plasmacytoid CD123(hi) precursors in blood and both myeloid CD11c(+) HLA-DR(+) fascin(+) (CD45RA(-)) DCs and putative plasmacytoid CD11c(lo) CD45RA(hi) DC precursors in liver and kidneys, without affecting organ function. DC in Flt3L-treated monkeys were concentrated in the glomeruli and interstitium of kidneys, and in the portal triads and parenchyma of liver. These DCs exhibited the phenotype of immature antigen-presenting cells (APCs; CD83(-) CD86(lo) CCR5(+) CCR7(-)). HGF-induced changes reversed significantly within 7 days of Flt3L withdrawal. Therapeutic protocols that mobilize donor hematopoietic cells should consider the influence of HGF on the APC constituency of prospective organ allografts.