Methodological challenges in the evaluation of prognostic factors in breast cancer.

Many studies are carried out in an effort to find factors that help explain the large unexplained variation in prognosis of breast cancer patients. The principles of good study design and analysis are less well appreciated for prognostic factor studies than for therapeutic trials. The oncology literature is full of results from studies of varying quality, often with conflicting findings. As a consequence, despite the large number of studies, there is still uncertainty about the importance of most prognostic factors. Few recently proposed prognostic factors for breast cancer have become widely accepted. This paper reviews the important methodological issues underlying such research. These issues are illustrated with examples from published studies and recent reviews of papers published in cancer journals. Guidelines are proposed for conducting and evaluating prognostic factor studies which should improve the quality of research in this important area.