Further analysis was carried out to calculate expected and observed rates for categories defined by breast cancer risk factors. Importantly, they markedly underestimated risk among women in the screening programme with a single first degree relative with breast cancer. With all models, the median of the estimated year risks was Phloretin significantly greater among women who developed breast cancer than in women who remained disease free.Until recently, there have been no stand alone comprehensive breast cancer risk assessment models able to account for all significant permutations of family history, reproductive history, and personal history of benign breast disease.However, it has not been independently validated and its value in the family history setting is still unclear.Furthermore, there is no clear evidence that even the established risk assessment models have ever been fully tested among women attending family history clinics.It also does not have an adjustment for other risk factors.Therefore, the previous work comparing the latter three models favourably is likely to be misleading, because while they give similar risk values in a risk assessment setting, all three underestimate risk.Conversely, all the models accurately predicted risk in women with multiple relatives affected with breast cancer. This implies that the effect of a single affected first degree relative is higher than may have been previously thought.As these are the only models to take account of ovarian cancer in their risk assessment algorithm, this confirms that ovarian cancer has a significant effect on breast cancer risk.Another possibility is that downward adjustments to heterozygote risk made due to the presence of unaffected female relatives are not counterbalanced by increases in risk in those without such unaffected relatives.It is not clear why such a modification to the effects of age at first birth should be made unless it is as a result of modifications made to the model after early results suggested an increase with BRCA mutation carriers.These results suggest that age at first live birth also has an important effect on breast cancer risk, while age at menarche perhaps has a lesser effect.The effect of pregnancy, years appeared to reduce risk by compared with the older and nulliparous groups, whereas at the extremes of menarche there was only a effect.The accuracy of these models for individual cases has significant implications in their use in clinical counselling.However, a large number of women who will remain disease free may also be advised to take such action.The effects of this on disease burden appear to be beneficial.Testing the various models in the family history setting provided very good access to a well maintained Aspirin cohort sample.However, the use of this sample did have some methodological weaknesses that should be addressed.However, it is likely that women identified on biopsy in other units would have been followed up if they had a biopsy showing proliferative disease and such information was sought in clinic.Indeed, only one cancer occurred in this group for the remainder of the full study population.The cohort used in this study comprised a moderate and high risk population with cancer incidence rates of times higher than the general population.

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