Gamma linolenic acid with tamoxifen as primary therapy in breast cancer

Effect of dietary GLA+/?tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts

“…32 In addition, the xenograft findings of lower ER expression on combined Tamoxifen and GLA are in agreement with the ER results from our pilot clinical trial. 11 In the latter we also demonstrated a significantly faster clinical response on combined treatment compared to tamoxifen alone, raising the possibility of an additive or synergistic growth-inhibitory action of these two agents via enhanced down-regulation of the ER machinery. In contrast to our clinical study in the xenograft work we have not been able to show the greater down-regulation of ER on combined T ϩ GLA to translate into slower tumour growth than on tamoxifen alone.…”

“…Combined treatment was found to have significant beneficial effects on both the clinical response and biological parameters of the tumours. 11 In the present study we have assessed the effect of dietary supplementation of GLA ϩ/Ϫ tamoxifen on the growth, ER expression and fatty acid profile of ERϩve human mammary tumours in a murine host. The advantages of the xenograft model over the clinical trial have been the opportunity to investigate GLA as sole therapy as well as the inclusion of a control arm receiving no active cancer treatment.…”

“…15 EFAs have previously been reported to modulate the structure and function of steroid hormone receptors, including the ER. 16 -19 The findings from our recent GLA clinical trial 11 of greater reduction in the expression of ER, the ERregulated protein bcl-2 and faster clinical response in patients receiving Tamoxifen ϩ GLA compared to Tamoxifen only has prompted us to investigate the outcome of GLA alone, as well as in addition to tamoxifen, on the expression of ER in the xenograft setting. Our results from the latter have complemented those of our clinical trial.…”

ω‐6 Polyunsaturated fatty acid γ‐linolenic acid (18:3n‐6) is a selective estrogen‐response modulator in human breast cancer cells: γ‐Linolenic acid antagonizes estrogen receptor‐dependent transcriptional activity, transcriptionally represses estrogen receptor expression and synergistically enhances tamoxifen and ICI 182,780 (Faslodex) efficacy in human breast cancer cells

“…Intravenous and oral treatments with GLA have achieved tumor responses in a number of advanced solid malignancies. [3][4][5] Enhanced lipid peroxidation has been proposed as one of the main mechanisms by which PUFAs such as GLA inhibit tumor cell growth. 1,2 Interestingly, GLA has also been shown to modulate the structure and function of steroid hormone receptors, 6 including the estrogen receptor (ER).…”

Epidermal growth factor receptor/HER2/insulin-like growth factor receptor signalling and oestrogen receptor activity in clinical breast cancer

“…The patients were elderly (>70 years), at stages I-II or locally advanced, where primary hormone therapy was deemed an appropriate initial treatment. Study of sequential biopsies was conducted in full accordance with the ethical principles for clinical trials, and every patient had given informed consent to undergo serial tumour biopsies as part of larger studies evaluating the phenotypic changes in breast carcinomas on primary endocrine therapy (Kenny et al 2000(Kenny et al , 2001. Response was assessed at 6 months by UICC criteria (CR or PR (complete or partial response); SD or PD (static or progressive disease)), and all patients remained on tamoxifen until progression of disease.…”