Tamoxifen and interferon-beta for the treatment of metastatic breast cancer

Abstract

It has been demonstrated, both in breast cancer cell lines and in metastatic breast cancer patients with cutaneous lesions that could be biopsied, that treatment with interferon beta (IFN-B) can increase expression of both estrogen (ER) and progesterone receptors (PgR). To evaluate the efficacy and toxicity of the combination of IFN and tamoxifen, 33 metastatic breast cancer patients were treated with the following regimen: IFN-B, 6.0 million units intramuscularly IU 3 times a week for two consecutive weeks followed by IFN-B 6.0 million IU im 3 times a week with concomitant tamoxifen 20 mg orally daily. Patients were pre and postmenopausal with median age of 60 years, median ECOG PS of 0, either ER positive or unknown, and had not received prior hormone therapy for metastatic disease. Overall objective response was observed in 9 (27%) patients. Complete response was observed in 2 cases and partial response in 7 patients. Median duration of response was 7 months (range 2-10). A higher response rate was observed in patients with predominantly soft tissue disease (38%) compared to patients with either dominant bone (18%) or visceral lesions (17%). Toxicity was mild and reversible: low grade fever in 30% of patients and flu-like symptoms in 9% of cases. It appears that IFN-B does not improve the efficacy of tamoxifen in an unselected population of metastatic breast cancer.

Cytokines in the Management of High Risk or Advanced Breast Cancer: An Update and Expectation

“…However, these studies have not shown significant prolongation of the expected overall survival. In the last pilot study [55], IFN did not improve the efficacy of tamoxifen in an unselected population of metastatic patients, who had not received prior palliative hormone therapy and had never received adjuvant tamoxifen or terminated it at least 12 months before. In all the studies with IFN , immunological effects were not recorded.…”

“…In four other pilot studies [52][53][54][55], IFN was given before and/or concomitant with tamoxifen. Most of the patients were with positive or unknown receptor status.…”

The Interactions Between Cancer Stem Cells and the Innate Interferon Signaling Pathway

“…IFN-β use as an anticancer drug is still under study, although ongoing phase III trials for melanoma (107,108) and for glioma (109) and glioblastoma (110) are being conducted with promising results. However, IFN-β treatment studies in metastatic breast cancer have not been as successful (111). IFN-γ has also been explored as a therapy for cancer, showing some contrasting results.…”

The role of Type I interferons in immunoregulation of breast cancer metastasis to the bone

“…Additionally, our study supports the use of the Irf7 signature to predict bone metastatic relapse in patients that may benefit from therapies aimed at restoring IFN-driven immune responses to prevent this. Although the clinical application of Type I IFN-based therapies has been tested unsuccessfully in small cohorts of breast cancer patients that already developed macrometastases, 10 we hypothesize that the best therapeutic window for investigating such therapies is in the adjuvant setting, when disseminated breast cancer cells have not yet formed macrometastases. Future studies based on the patient population that would most likely benefit from IFN-based therapies and the most appropriate therapeutic setting for administering such treatments are imperative.…”