Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

Triplet morbidity and mortality in a large case series.

OBJECTIVE: A significant increase in the triplet birth rate has occurred recently. This rise is of concern, as these infants are historically reported to be at risk of adverse outcome. Thus, we examined the outcome of triplet births in a large contemporary case series. STUDY DESIGN: Since 1993, detailed clinical data have been collected on all patients admitted to our Neonatal Intensive Care Unit. We retrospectively analyzed this database to examine triplet outcome. RESULTS: A total of 51 consecutive sets of triplets were born over a 9-year period. The mean birth weight for triplets was 1789+/-505 g, mean gestational age was 32.6+/-2.7 weeks, with discordancy present in 17.6% of neonates. Complications of prematurity were infrequent. Triplet survival to discharge was 96%. CONCLUSIONS: This large contemporary case series of triplets demonstrates excellent survival with low associated morbidity. These data suggest that there may no longer be medical justification for offering selective fetal reduction to parents with triplet pregnancies.     

Longitudinal,population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status,treatment and comorbidity

Background  

Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods.     

Follow up study of children born elsewhere but attending schools in Seascale, West Cumbria (schools cohort)

Records on 1546 children who were identified as having attended schools in Seascale up to November 1984 and were born since 1950 but not in the civil parish were studied. These children lived in or near Seascale for a period of time while they were attending one or more of three local schools and are an additional group to the 1068 children who were identified as born to mothers resident in Seascale in an accompanying study. Even though some of the schoolchildren apparently remained in the village for a short period only all but 7% were followed up through the National Health Service Central Register. Mortality among these children to 30 June 1986 is comparable to that expected at national rates. From all causes there were 10 observed deaths compared with 12.69 expected--a ratio of 0.79 (95% confidence interval 0.38 to 1.45)--and from cancer one observed death compared with 2.04 expected--a ratio of 0.49 (95% CI 0.01 to 2.73). No deaths from leukaemia or lymphoma were reported, but only 0.83 was expected. Since 1971 (the year when cases of cancer were first notified to the NHS Central Register) three non-fatal cases of cancer were reported, including two lymphomas, compared with 2.04 expected and two cases of carcinoma in situ of the cervix compared with 1.79 expected. In addition, there was a case of leukaemia among the schoolchildren which was known previously and had been diagnosed in 1968. There is an interesting difference between the results of this study and the results of the study of children born to mothers who were resident in Seascale. In the latter study there was an excess of leukaemia and of other cancers, but a similar finding is not apparent among children who spent some time at schools in Seascale but were born elsewhere. This raises the question of whether one or more aetiological factors in childhood cancer were acting on a locality specific basis before birth or early in life. This cannot be answered from these cohort studies, but it is hoped that the case-control study that is under way in West Cumbria will provide relevant information.