Steroid receptor enhancement by natural interferon-β in advanced breast cancer

Sica, Gigliola; Iacopino, Fortunata; Lama, Gina; Amadori, Dino; Baroni, Mario; Sardo, F. Lo; Malacarne, P; Marchetti, Paolo; Pellegrini, A; Zaniboni, Alberto; Cuna, G. Robustelli della

doi:10.1016/0959-8049(93)90378-s

Cited by 19 publications

(6 citation statements)

References 17 publications

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“…For this reason, we tried to find an approach that could improve the efficacy of TAM. Our aim was to render breast cancer cells more susceptible to hormonal therapy and to improve the immune function with the use of ß-IFN and R. Sica et al demonstrated that ß-IFN may induce the increase in ER in mammary cancer cell lines and, in agreement with other authors, they showed that ß-IFN treatment induce increase in both ER and PgR in cutaneous metastases of breast cancer patients (27,28). The receptor increase may be potentially linked to an enhanced hormone-sensitivity.…”

Section: Discussionsupporting

confidence: 62%

Beta-interferon, retinoids and tamoxifen in metastatic breast cancer: Long-term follow-up of a phase II study

Recchia

Sica²,

Candeloro³

et al. 2009

Oncol Rep

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Abstract. Based on a series of in vitro data, including the additive and/or synergistic antiproliferative effect of interferon and tamoxifen on breast cancer cell lines, and on clinical reports, we designed a pilot phase II study to test the activity and toxicity of simultaneous administration of ß-interferon (ß-IFN), retinoids (R) and tamoxifen (TAM) as a salvage therapy in a group of patients with metastatic breast cancer (MBC). Herein we describe the outcome of this cohort of patients after a median follow-up of 150 months. Sixty-five stage IV breast cancer patients, 13 pre-treated with hormones, 38 with chemotherapy and 15 with both, received, as a salvage therapy, TAM, ß-IFN and R. Among 65 evaluable patients, 36 achieved a clinical response (55.5%) (95% c.i. 42-67.7%). Toxicity was moderate and mainly hepatic. Median progression-free and overall survival, which did not show any statistically significant difference in patients with different estrogen and progesterone receptor content, were 43 months and 47.9 months, respectively. In conclusion, the study shows that long-term treatment with TAM, ß-IFN and R in MBC is feasible, has moderate toxicity and seems to give a long-term benefit, irrespective of the receptorial status.

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Section: Discussionsupporting

confidence: 62%

Beta-interferon, retinoids and tamoxifen in metastatic breast cancer: Long-term follow-up of a phase II study

Recchia

Sica²,

Candeloro³

et al. 2009

Oncol Rep

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“…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.…”

Section: Interferonsmentioning

confidence: 99%

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

Carpi¹,

Nicolini²,

Antonelli³

et al. 2009

CCDT

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Some cytokines (interleukin (IL)-2, IL-11, transforming growth factor(TGF)beta) stimulate, while others (IL-12, IL-18, Interferons (IFNs)) inhibit breast cancer proliferation and/or invasion. So far IL-2, IFNalpha, IFNbeta and occasionally IFNgamma, IL-6, IL-12 have been used for the treatment of advanced breast cancer either to induce or increase hormone sensitivity and/or to stimulate cellular immunity. Only two long term pilot studies suggest that IL-2 and IFNbeta can improve clinical benefit and/or overall survival of metastatic breast cancer patients with minimal residual disease after chemotherapy or with disseminate disease non progressing during endocrine therapy. These results have been interpreted assuming that tumour microenvironment impairs the immune system of the host. Consequently, minimal disease or intense cytostatic effects following chemo or endocrine therapy, respectively, permit the patient's immune system to respond to the stimulatory effect of the cytokines. Therefore a prospective, phase III, randomised, simple blind trial has been planned. The aim is to assess whether the addition of IFNbeta and IL-2 to standard hormone therapy in postmenopausal patients with metastatic breast cancer and positive or unknown positive receptors prolongs the clinical benefit and survival since the metastatic diagnosis and the beginning of first line salvage antiestrogen therapy, compared with the results achieved with standard hormone therapy alone. If this immunotherapy prolongs survival of endocrine dependent metastatic breast cancer patients, IL-2 and IFNbeta can also be evaluated as adjuvant treatment of patients with positive estrogen receptors.

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“…Prior reports have indicated that the response to tamoxifen could be improved by the addition of IFN-B: in 43 metastatic breast cancer patients partially responsive, stable, or progressing during tamoxifen treatment, an objective response was observed in 26% of cases after the addition of IFN-B to the treatment program [13]. With tamoxifen and In addition an increase in ER and PgR receptors was observed in patients with cutaneous metastases subjected to repeated biopsies [5]. In the present series, tamoxifen combined with low dose IFN-B led to an objective response in 9 of 33 (27%) unselected pre and postmenopausal metastatic breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…In fact Sica and coworkers observed that interferon beta (IFN-B) inhibited growth of the CG-5 human breast cancer cell line, a variant of MCF-7 with high estrogen receptor (ER) expression, and that after 5 days of treatment with low doses of IFN-B both E R and progesterone receptor (PgR) content was increased [4]. IFN's have been reported to increase E R content in breast cancer tissue [5]. In a small group of metastatic breast cancer patients, Pouillart et al demonstrated that IFN-B determined an increase in E R expression in 2 of 2 patients and PgR content in 5 of 6 patients whose soft tissue metastases were biopsied prior to and following treatment [6].…”

Section: Introductionmentioning

confidence: 99%

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

Repetto

Giannessi

Campora

et al. 1996

Breast Cancer Res Tr

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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.

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Steroid receptor enhancement by natural interferon-β in advanced breast cancer

Cited by 19 publications

References 17 publications

Beta-interferon, retinoids and tamoxifen in metastatic breast cancer: Long-term follow-up of a phase II study

Beta-interferon, retinoids and tamoxifen in metastatic breast cancer: Long-term follow-up of a phase II study

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

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

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