Status of aromatase inhibitors in relation to other breast cancer treatment modalities.

Abstract

Aromatase is one of the key enzymes possibly linked with the perpetuation or even initiation of breast cancer. Modulation of its activity by the new generation inhibitors has resulted in increased responses and improved therapeutic ratio compared with those of parent aromatase inhibitors. More recent trials have shown promising results with regard to improved therapeutic ratio compared with what is seen with presently accepted second-line hormonal approaches. Present data and laboratory research indicate that new aromatase inhibitors have the potential to play an important role as adjuvants, and possibly in the prevention of human breast cancer. It is probable that it may be as adjuvants that their real therapeutic strength in terms of a beneficial impact on survival may be realized. The absence of estrogen agonist activity of new aromatase inhibitors on lipid and bone metabolism calls for more clinical studies having late mortality in breast cancer survivors as the ultimate outcome objective; in this regard, interaction of new aromatase inhibitors with new selective estrogen receptor modulators looks promising. Achievement of these outcomes, and understanding of interactions with other Endocrine-Related Cancer (1999) 6 277-291 therapies, await the termination of present trials and the start of new initiatives.

Enhanced formation of non-phenolic androgen metabolites with intrinsic oestrogen-like gene transactivation potency in human breast cancer cells: a distinctive metabolic pattern

“…Although the aromatisation of androgens in breast cancer cells has remained controversial, low, but reproducible aromatase activity has been detected in MCF-7 cells (Sonne-Hansen & Lykkesfeldt 2005). To avoid oestrogen formation, several aromatase inhibitors have been widely used in therapeutic schemes in breast cancer (Coombes et al 1987, Santen et al 1990, Demers 1994, Goss 1999, Ragaz 1999, Sasano et al 1999, although the oestrogen-like effects of androgens are not completely suppressed by this treatment (Brodie et al 1977, Brodie & Longcope 1980, Coombes et al 1984, Wing et al 1985, Lippman 1998, Buzdar 2002, Lønning 2004, Brueggemeier et al 2005. These observations raise the important question as to whether androgens are locally bioconverted to non-phenolic metabolites with intrinsic oestrogenic activities.…”

Efficacy of First-Line Letrozole Versus Tamoxifen as a Function of Age in Postmenopausal Women with Advanced Breast Cancer

“…However, recent studies have found third-generation aromatase inhibitors to be more effective than [5], or at least as effective as, tamoxifen [6,7] in the first-line treatment of advanced breast cancer. These drugs are very selective and potent in the suppression of aromatase activity [8].…”

Expresión de los ARNm que codifican para las enzimas que biotransforman a la testosterona en células humanas de carcinoma mamario

“…(Sonne-Hansen y Lykkesfeldt, 2005). De hecho para detener la formación de estrógenos, han sido utilizados ampliamente varios inhibidores de la aromatasa en esquemas terapéuticos en cáncer de mama (Coombes et al, 1987;Santen et al, 1990;Demers, 1994;Goss, 1999;Ragaz, 1999;Sasano et al, 1999), aún cuando los efectos de tipo estrogénico de los andrógenos no son completamente suprimidos por este tratamiento (Brodie et al, 1977;Brodie y Longcope, 1980;Coombes et al, 1984;Wing et al, 1985;Lippman, 1998;Buzdar, 2002;Lonning, 2004;Brueggemeier et al, 2005).…”