[Tissue-based markers of prognosis in breast cancer]

Precise prognostication represents one of the essential but still unsolved challenges in breast cancer pathology. There is a striking discrepancy between the plethora of suggested markers that have proved useful in mono-centre retrospective studies, including molecular expression arrays and the only small number of parameters applied in clinical decision finding. When adjuvant therapy is considered clinicians still rely predominantly on traditional parameters like staging and hormonal receptor status. Another traditional marker which has proven its strength in mono-centre studies but is compromised by subjectivity and limited reproducibility is provided by grading. We have conducted a study on how traditional grading markers can be objectified and adapted to small amounts of tissue which have become custom with the wide-spread use ob needle biopsies. A modified grading scheme replacing mitosis counting by Ki-67 immunohistochemistry and nuclear pleomorphism by digital determination of nuclear size was applied to 346 cases of breast cancer with a median follow-up of 6 years in a tissue micro-array. A highly significant correlation with overall and disease-free survival could be established in this retrospective study although not more than 1.4 square millimeters of tissue were evaluated. When combined with nodal status and progesterone receptor evaluation a subgroup free of any relapse could be identified. It is concluded that standardized and objectified application of grading as a traditional tissue-based marker of prognosis can improve its impact considerably even in limited amounts of tissue.