The early discrimination of clinically aggressive breast cancer from indolent disease would be clinically useful. Some human breast cancers express haptoglobin-related protein (Hpr), the HPR gene product, or a substance that shares epitopes with it. We retrospectively examined the association between the expression of Hpr and the recurrence of cancer in 70 patients with early breast cancer (Stage I or II) treated by mastectomy from 1977 through 1985, using immunohistochemical analysis of routinely processed paraffin-embedded tissue and evaluating it without knowledge of the patients' status. The expression of Hpr epitopes was associated with earlier recurrence according to life-table analysis (P<0.0002). Progesterone-receptor status (determined in 64 patients), tumor size, clinical stage, axillary-lymph-node status, mitotic index, and tumor necrosis also predicted recurrence, but multivariate analysis showed that Hpr-epitope expression was an independent prognostic factor. Since both Hpr status and progesterone-receptor status were independent predictors of recurrence, they could be combined to stratify the cases further: breast cancer was found to have recurred in 11 of 12 patients (92 percent) who were positive for Hpr and negative for progesterone receptors, in 5 of 11 (45 percent) who were positive for Hpr and positive for progesterone receptors, and in 9 of 41 (22 percent) who were negative for Hpr, in whom progesterone-receptor status had little effect. We conclude that Hpr-epitope expression is a clinically important predictor of the recurrence of cancer in patients with early breast cancer, especially in combination with progesterone-receptor status. (N Engl J Med 1989;321:636-41.) AT the time of diagnosis, at least 25 percent of patients with early breast cancer have clinically undetectable metastases. If patients with this status could be identified at the time of diagnosis, one could apply early, intensive chemotherapy to women with clinically occult systemic breast cancer. Traditional associations between the histopathological features and clinical course of the disorder cannot be used to differentiate between clinically aggressive and clinically indolent disease.1 In contrast, several recent studies have demonstrated a relation between changes in oncogenes and prognosis. For example, in some studies, amplification of the HER-2/neu oncogene in patients with breast.
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