Is expression or activation of Src kinase associated with cancer-specific survival in ER-, PR- and HER2-negative breast cancer patients?

The aim of the current study was to assess the expression levels of c-Src and phosphorylated Src kinase in human breast cancers and to establish if these are linked to oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status or patient survival. Tissue microarray technology was used to analyze 314 breast cancer specimens. Immunohistochemistry was performed using antibodies to c-Src, Y419Src, and Y215Src, and expression was assessed using the weighted histoscore method. High cytoplasmic c-Src kinase and high membrane phosphorylated activated Y419Src kinase was associated with decreased disease-specific survival. In contrast, phosphorylated activated nuclear and cytoplasmic Y215Src kinase expression levels were significantly associated with improved disease-specific survival. When the cohort was subdivided according to ER/PR/HER2 status, the ER-negative subgroup (105 patients) was associated with improved disease-specific survival and was found to be independent by multivariate analysis with a hazard ratio of 0.4 (interquartile range 0.2-0.8). High cytoplasmic c-Src expression was associated with decreased survival; high expression of activated c-Src (Y215) was associated with improved survival. This was potentiated in the ER/HER2-negative subgroup. Hence, administration of Src kinase inhibitors aiming to decrease phosphorylation should be approached with caution, especially in ER-negative patients. It is therefore essential to appropriately identify with the correct biomarkers which patients are most likely to respond to Src inhibitors.

Increasing incidence of breast cancer: distinguishing between the effects of birth cohort and a national breast screening programme.

The incidence of breast cancer in post-menopausal women has been affected by the introduction of national breast screening programmes. The study describes the incidence of breast cancer in Scottish women aged 50-64 by year of birth before, during, and after the prevalent round of screening. Breast cancer registrations in Scotland for women aged 45-69 years from 1977 to 2003 were obtained. Birth cohort incidence rates were calculated and interpreted in the light of screening patterns at particular calendar time points. In the years before screening, there was a small rise in breast cancer incidence by birth cohort in women aged 50-54 which was not seen in other ages. During the prevalent screening round, incidence increased significantly with increasing birth cohort and thereafter continued rises in incidence by birth cohort occurred. The observed rise in breast cancer incidence among post-menopausal women is likely to be due to both screening effects and a true increase in incidence.

Breast cancer incidence trends in deprived and affluent Scottish women.

OBJECTIVE: Breast cancer is commoner in the affluent and breast cancer rates in many countries are rising; it remains unclear whether this incidence rise is consistent across the different socio-economic groups. The rising incidence of breast cancer may be related to changes in population risk factor profiles. This study aimed to determine breast cancer incidence trends in women of different socio-economic categories and whether these trends were related to breast cancer risk factor trends. DESIGN: Data on breast cancer incidence rates by deprivation quintile in Scotland 1991-2000 were analysed using linear regression. Data on first births at late maternal age, BMI trends (based on the Scottish Health Surveys) and breast screening uptake trends in the different categories were also analysed and their relation to breast cancer incidence trends explored. POPULATION AND SETTING: Breast cancer incidence data was based on all women in Scotland. BMI data was based on representative cross-sectional survey data from the Scottish Health Surveys-women in the 1995, 1998 and 2003 surveys were 16-64, 16-74 and aged 16 and over, respectively. First birth data was based on all women aged 35-39 in Scotland. Breast screening uptake data was studied in women of screening age, that is, aged 50-64. RESULTS: Breast cancer incidence rates in Scottish women are rising in parallel across all socio-economic categories and the incidence gap between deprived and affluent still remains. Since the late 1980s, numbers of first birth in Scottish women aged 35-39 have risen dramatically, especially in the affluent, but numbers were stable before this. The prevalence of obesity and mean BMI has increased over time in all socio-economic classes but BMI continues to be higher in the deprived. Uptake of screening invitations has increased in all socio-economic groups. CONCLUSIONS: Breast cancer is rising in women of all socio-economic status in Scotland and the deprived-affluent gap remains. Trends in late age at first pregnancy, prevalence of obesity and screening uptake do not fully explain the observed trends.