Distant metastases from breast cancer are incurable. In endocrine-responsive patients antiestrogens are commonly administered as first and second line therapy. Regrettably, tumor growth becomes resistant to this relatively innocuous therapy. Beta-interferon was unsuccessfully added to tamoxifen to induce estrogen receptor enhancement. In mice, interleukin-2 added to tamoxifen increased their mutual anti-tumor activities. Nevertheless, no effective clinical application has been developed. We

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... ted an exploratory clinical trial based on the association of these immunostimulating cytokines with antiestrogens for first line salvage therapy of hormone dependent breast cancer with distant metastases. Twenty-six consecutive breast cancer patients with distant metastases, 23 of which had metastases at multiple sites, were studied for responsiveness to treatment with first line salvage antiestrogen therapy, combined with beta-interferon and interleukin-2 immuno-therapy. Clinical response and survival were compared with that of 30 consecutive historical control patients treated with antiestrogen therapy alone. Controls showed, as expected, a median duration of response, a median survival time after treatment, and after diagnosis of distant metastases, of 16, 31 and 34 months, respectively. After a mean follow-up of 62 ± 36 months (range 17-155), the interval times in the non-control patients were 61 (P < 0.001), 101 (P < 0.000001) and 106 (P < 0.000001) months. Two long-term survivors appeared to be cured after 155 and 94 months from the time of diagnosis with multiple bone metastases. Nineteen of the patients treated with beta-interferon and interleukin-2 have survived. Hormone immuno-therapy was given in an outpatient setting and was very well tolerated. These data suggest that immunotherapy plays an important role in endocrine-dependent metastatic breast cancer.