[en] Purpose: Over-expression of the HER-2 neu oncoprotein in breast cancer has been shown to have prognostic significance with respect to disease-free and overall survival. The association of local recurrence in the conservatively treated breast with the HER-2 neu oncogene has not been extensively evaluated. The purpose of this study is to determine the prognostic significance of over-expression of the HER-2 neu oncogene with respect to ipsilateral breast tumor recurrence (IBTR) in the conservatively treated breast cancer patient. Methods and Materials: Over 1,000 patients treated with conservative surgery followed by radiation therapy to the intact breast served as the patient population base for this study. Twenty patients who sustained an IBTR as the first and only site of failure comprised the index case population base for this study. In order to maximize follow-up and eliminate the confounding effects of adjuvant therapy, only patients who were treated prior to 1985 and who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive patients with IBTR, the patient database was searched for 20 matching control patients who did not sustain an IBTR. Each control patient was matched to the index case with respect to age (within five years), menopausal status, follow-up (date of diagnosis within three years), primary histology, axillary nodal status, and primary tumor size. Both index cases and the matched control group received radiation therapy to a total dose of 6400 cGy to the tumor bed, received no adjuvant systemic therapy and had not sustained systemic relapse at the time of evaluation of the study. Following identification of the 20 IBTR cases and 20 matched controls, the paraffin-embedded blocks were processed for immunohistochemical staining of the HER-2 neu oncoprotein. The pathologists processing, staining and grading the specimens were blinded as to the clinical information. Each slide was rated on a three point scale, 0 - no stain, 1+ - light staining, and 2+ - heavy staining. For this analysis, a value of 2+ was considered over-expression and positive, while 0 and 1+ were considered negative values. Results: Of the 20 index cases, with each of the matched controls, 16 were evaluable for analysis. The four cases which were eliminated had inadequate paraffin-embedded material in either the case or the match control for adequate staining. As expected, and by design of the study, the index case group and control group had similar age (52 years index vs 51.4 control), follow-up (10.8 years index vs 10.5 years control) and histologies. A total of nine of the 16 index cases (56%) exhibited over-expression of HER-2 neu, while only three of the 16 control cases (19%) demonstrated a high immunoreactivity. The difference between the index and control cases was statistically significant by a Pierson Chi Square analysis at the p=.03 level. Conclusion: In this matched case control study, over-expression of the HER-2 neu oncoprotein appears to have prognostic significance with respect to local relapse in the conservatively treated breast. The clinical implications of this must take into consideration that these patients were treated in an era when there was no attempt to obtain free surgical margins and adjuvant systemic therapy was not employed in any of these patients. The correlation of over-expression of HER-2 neu with other prognostic factors for local recurrence such as extensive intraductal component, major lymphocytic stromal reaction, tumor necrosis and patient age needs to be explored and evaluation of HER-2 neu as a prognostic factor in a multivariate analysis with other prognostic factors for local recurrence warrants further investigation