The major thrust of this proposal is to attempt to confirm (in an independent set of patients) the reported results for CALGB-8641 which suggested that the level of expression of c-erbB-2 may allow prediction of the efficacy of adjuvant CAF. The results from CALGB-8541 suggest that """"""""high dose CAF reduces the relative hazard of recurrence by more than 50% in the patients whose tumors had high levels of c-erbB-2 expression. The efficacy of """"""""high dose CAF was not different than """"""""low"""""""" dose CAF in patients with low expression of c-erbB-2. These results have potential practical implication s to the clinician and patient, for although this trial's results (viewed without knowledge of c-erbB-2) suggest that all node positive patients should get """"""""high"""""""" dose CAF (the most effective therapy on average), knowledge of c-erbB-2 levels may allow nearly 2/3 of such women to be spared the additional cost and toxicity of the """"""""high"""""""" dose regimen. This proposal will offer supportive evidence for the practical use of c- erbB-2 in the selection of patients who would particularly benefit from CAF. This study will be conducted in patients participating in SWOG-8814 (INT-0100). In this study, postmenopausal, node positive, ER+ patients are randomized between Tamoxifen alone or """"""""high dose CAF plus Tamoxifen. This is the only active trial in which patients are being randomized between a CAF-based chemotherapy or no chemotherapy. C-erbB-2 levels will be measured by immunohistochemical (IHC) staining of paraffin block material. The central hypothesis is that patients with elevated c-erbB-2 will have striking improvements in DFS and OS when given CAF, but hat patients without over-expression of c-erbB-2 will have much less or perhaps no benefit from adjuvant therapy with CAF. If the results of CALGB-8541 ar confirmed. Postmenopausal node positive ER+ women (approximately 30,000 women per year) could better choose among the adjuvant therapy options. As part of the proposed work, this proposal plans to take advantage of the paraffin block material to explore the use of other markers to predict apparent efficacy of CAF including: indicators correlated with proliferation, P53, Ki67, S-phase and grading systems; a marker of resistance to doxorubicin, Heat Shock Protein 27; and a marker of paracrine effects, angiogenesis. Funding is also requested for the IHC staining for 6 additional markers, to be selected from these general categories on the basis of ongoing studies. In order to complete a panel of prognostic factors which might in the future be done only on paraffin block material, IHC ER and PgR will additionally be measured. The overall goal of this work is to contribute to the knowledge that will allow a panel of prognostic factors to be used to predict which patients will benefit most from the currently available therapeutic options.
