Zoladex: Endocrine and therapeutic effects in post-menopausal breast cancer

Harris, Adrian L.; Carmichael, J.; Cantwell, B. M. J.; Dowsett, Mitch

doi:10.1038/bjc.1989.19

Cited by 47 publications

(10 citation statements)

References 20 publications

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“…In addition, recent discovery of LH-RH receptors on some mammary tumor cell membranes [9], human BC cells [10], as well as other tumor cells [11] suggested the direct antitumor effect of LH-RH analogues. This is sup ported by the finding of Harris et al [12], who obtained the therapeutic response in postmenopausal BC patients treated with Zoladex, and by the effectiveness of Zoladex in SR-negative patients [13], It is concluded that these findings would enlarge the oncological application of LH-RH agonistic analogues [14], Triptorelin is one of the most powerful agonistic ana logues, available in a lyophilized form, which requires daily subcutaneous injections, and in a sustained release formulation for intramuscular injection delivering a daily dose of 100pg during 28 days. Its long-acting or depot formulation consists of spherical microcapsules in which the analogue is distributed in a biodegradable biocompat ible polymer [15], The clinical effectiveness in BC pa tients as well as the endocrinological effects of the triptor elin long-acting form is equal to the daily subcutaneous form [15,16].…”

Section: Introductionsupporting

confidence: 63%

Therapeutic and Endocrine Effects of Decapeptyl®, Synthetic LH-RH Agonistic Analogue in Premenopausal Women with Metastatic Breast Cancer

Nešković-Konstantinović

Vuletić²,

Nikolić-Stanojević³

et al. 1994

Oncology

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Twelve premenopausal patients with advanced breast cancer were entered into pilot phase II study to assess efficacy, toxicity and influence of the synthetic LH-RH agonistic analogue D-Trp⁶-LH-RH (Decapeptyl®) on the patients’ hormonal status. The patients, aged 33-50, with newly diagnosed stage IV or recurrent breast cancer were not previously treated by any kind of endocrine therapy. Steroid receptor status was known in 9 patients. Decapeptyl was applied monthly at a dose of 3.75 mg i.m. until progression. The therapeutic response was evaluated in 11/12 patients. Partial remission was achieved in 5, stabilization in 3, and 3 consecutive patients failed to respond. The best therapeutic response was obtained in patients with pleuropulmonal and soft-tissue involvement, aged 41-45, including those with incomplete ovarian suppression, and regardless of steroid receptor status. The mean serum gonadotropins and estradiol levels were suppressed. The treatment was free of any side effects, except hot flushes in 7 patients.

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Section: Introductionsupporting

confidence: 63%

Therapeutic and Endocrine Effects of Decapeptyl®, Synthetic LH-RH Agonistic Analogue in Premenopausal Women with Metastatic Breast Cancer

Nešković-Konstantinović

Vuletić²,

Nikolić-Stanojević³

et al. 1994

Oncology

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“…The treatment of breast cancer has been aided by the development of the estrogen receptor assay, which has been used as a prognostic tool to determine whether a particular tumor is likely to respond to endocrine therapy [26--28]. The first line of treatment for estrogen receptor positive tumors has been ablation therapy, using anti-estrogens [29][30][31], inhibitors of steroid synthesis [32], GnRH analogues [33,34], and sequential hormone therapy [35,36]. These therapies have had some limited success in increasing the five-year survival rate, although recurrent tumors are usually hormone-insensitive and therefore no longer amenable to hormone therapy.…”

Section: A Clinical Backgroundmentioning

confidence: 99%

Active cell death in hormone-dependent tissues

et al. 1992

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Active cell death (ACD) in hormone-dependent tissues such as the prostate and mammary gland is readily induced by hormone ablation and by treatment with anti-androgens or anti-estrogens, calcium channel agonists and TGF beta. These agents induce a variety of genes within the hormone-dependent epithelial cells including TRPM-2, transglutaminase, poly(ADP-ribose) polymerase, Hsp27 and several other unidentified genes. Not all epithelial cells in the glands are equally sensitive to the induction of ACD. In the prostate, the secretory epithelial cells that are sensitive to hormone ablation are localized in the distal region of the prostatic ducts, and are in direct contact with the neighboring stroma. In contrast, the epithelial cells in the proximal regions of the ducts are more resistant to hormone ablation, probably because the permissive effects of the stroma are attenuated by the presence of the basal epithelial cells, which are intercalated between the epithelium and stroma. The underlying biology of ACD in prostate and mammary glands, and its relevance to hormone resistance, is discussed in this review.

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“…However, the therapeutical effects of GnRH analogs on breast tumor regression in postmenopausal women cannot be explained on the basis of suppression of gonadal activity, since their serum gonadal steroid levels are already reduced [ 1,2]. Indeed, there are several studies describing direct effects of GnRH analogs on the growth of mammary tumor cells in culture [3- Recently [6], we have demonstrated that the GnRH gene is expressed in the mammary gland of the rat.…”

Section: Introductionmentioning

confidence: 99%

Expression of the gene for the receptor of gonadotropin‐releasing hormone in the rat mammary gland

et al. 1996

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Recent findings have demonstrated that the GnRH gene is expressed in the mammary gland of pregnant and lactating rats but not of virgin rats. Indeed, significant concentrations of biologically active GnRH have been found in milk of human, cow, sheep and rat. We have, therefore, looked for expression of the GnRH receptor in the rat mammary gland. By reverse transcription (RT)-PCR amplification, we have demonstrated the presence of GnRH receptor mRNA in mammary gland samples derived from virgin, pregnant and lactating rats. The GnRH receptor transcript cloned from the mammary gland was sequenced and found to have an identical coding region to the one cloned from the pituitary gland. In addition, we have found that the mammary gland, as the pituitary gland, contains at least two transcripts having the same coding region but different 5' non-coding regions. Binding studies, however, could demonstrate only low-affinity binding sites. These results, therefore, suggest that the regulation of the GnRH receptor occurs posttranscriptionally rather than at the level of transcription.

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Zoladex: Endocrine and therapeutic effects in post-menopausal breast cancer

Cited by 47 publications

References 20 publications

Therapeutic and Endocrine Effects of Decapeptyl®, Synthetic LH-RH Agonistic Analogue in Premenopausal Women with Metastatic Breast Cancer

Therapeutic and Endocrine Effects of Decapeptyl®, Synthetic LH-RH Agonistic Analogue in Premenopausal Women with Metastatic Breast Cancer

Active cell death in hormone-dependent tissues

Expression of the gene for the receptor of gonadotropin‐releasing hormone in the rat mammary gland

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