Interferons (IFNs) are cytokines that possess potent anti-viral and immunoregulatory activities. In contrast, their potential role(s) in anti-bacterial defense and neutrophil activation mechanisms is less well explored. By comparing gene expression patterns between immature and mature human neutrophils, we obtained evidence that intracellular proteases and other anti-bacterial proteins are produced at earlier stages of maturation, whereas the genes for receptors and signaling molecules required for the release of these effector molecules are preferentially induced during terminal differentiation. For instance, mature neutrophils strongly expressed genes that increase their responses to type I and type II IFNs. Interestingly, granulocyte/macrophage colonystimulating factor was identified as a repressor of IFN signaling components and consequently of IFN-responsive genes. Both IFN-␣ and IFN-␥ induced strong tyrosine phosphorylation of STAT1 in mature but not in immature neutrophils. Functional in vitro studies suggested that IFNs act as priming factors on mature neutrophils, allowing the formation of extracellular traps upon subsequent stimulation with complement factor 5a (C5a). In contrast, both IFN-␣ and IFN-␥ had only little capacity to prime immature cells in this system. Moreover, both IFNs did not have significant anti-proliferative effects on immature neutrophils. These data contribute to our understanding regarding changes of gene expression during neutrophil differentiation and IFNmediated anti-bacterial defense mechanisms.

Endocrine treatments have been used in breast cancer since 1896, when Beatson reported on the results of oophorectomy for advanced breast cancer. In the second half of the last century, different endocrine-based compounds were developed and, in this review, the role of the selective estrogen receptor modulators (SERMs) and selective estrogen receptor down regulators (SERDs) in the postmenopausal setting are discussed. Tamoxifen is the most investigated and most widely used representative of these agents, and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting, and for the prevention of the disease. Its role has been challenged in recent years by the introduction of third-generation aromatase inhibitors that have proven higher activities than tamoxifen with different toxicity patterns. Several other SERMs have been investigated, but none have been clearly superior to tamoxifen. SERDs act as pure estrogen antagonists and should compare favourably to tamoxifen. For the time being, they have been used in the treatment of advanced breast cancers and their role in other settings still needs investigation. The increased use of aromatase inhibitors as first-line endocrine therapy has resulted in new discussions regarding the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies in hormone-sensitive breast cancer remains a very important research issue.

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