estrogen positive cancer

[maryfdanal]

I may be recommended for Tamoxofin for recurrent ovarian cancer if the tests show that it is Estrogen positive. I am having trouble finding much about this on the web. Is this a common treatment? Effective? Safe? anyother information would be appreciated

[Annekathryn Goodman, M.D.]

Hi there,
most information in the literature is related to breast cancer and tamoxifen. However, tamoxifen and other SERMs (selected estrogen receptor modulators) have been used to treat ovarian cancer. I have pasted a few articles. One is a basic science article on the mechanism of action. The other two are reviews of existing clinical experience. There are very few side effects to tamoxifen. We usually use it as a maintainenece therapy.
best wishes


Cytokine. 2009 Jun;46(3):382-91. Epub 2009 Apr 28. Links
Reciprocal regulation of 17beta-estradiol, interleukin-6 and interleukin-8 during growth and progression of epithelial ovarian cancer.Yang J, Wang Y, Gao Y, Shao J, Zhang XJ, Yao Z.
Department of Immunology, Tianjin Medical University, Heping District Qixiangtai Road No. 22, Tianjin 300070, PR China.

Estrogens have been associated with risk for epithelial ovarian cancer (OVCA). Both IL-6 and IL-8 are also likely involved in the progression of OVCA. In order to discover the underline molecular mechanism, we investigated the modulation of estrogen and two cytokines in the growth and progression of epithelial OVCA. In these studies, the effect of 17beta-estradiol (E(2)) on the expression levels of IL-6, IL-8 and their receptors was investigated. The effect of IL-6 and IL-8 on activation of estrogen-responsive promoter as well as estrogen receptor (ER)alpha and ER beta expression was also analyzed. Gene expression profile analysis revealed that CAOV-3 and OVCAR-3 cells, which express ER, IL-6 and IL-8 receptors, are suitable model for this study. We found that E(2) not only enhanced IL-6 and IL-8 production via NF-kappaB signaling pathway, but also modulated their respective receptor expression. Tamoxifen (Txf), an ER antagonist, completely abolished E(2)-stimulated cell growth and the expression of IL-6 and IL-8. IL-6/IL-8-induced cell proliferation was completely blocked by their specific neutralizing antibodies, which partially inhibited E(2)-induced cell growth. In the absence of estrogen, both cytokines activated estrogen-responsive promoter, which was completely blocked by Txf, and caused a dose-dependent ER alpha increase and ER beta decrease. Pretreatment of OVCAR-3 with p38 MAPK, MEK1/2 or ErbB2 MAPK inhibitors, respectively, blocked IL-6-mediated induction of estrogen-responsive promoter while Src inhibitor blocked IL-8-induced activation of estrogen-responsive promoter. These results provide a novel mechanism that estrogens, IL-6 and IL-8 may form a common amplifying signaling cascade to modulate OVCA growth and progression. Estrogen-induced OVCA proliferation is partially occurring via enhanced IL-6 and IL-8 production and modulated their receptors, and IL-6/IL-8 could also promote OVCA growth through an ER alpha pathway


Best Pract Res Clin Obstet Gynaecol. 2008 Apr;22(2):407-21. Epub 2007 Sep 19. Links
Hormonal therapies and gynaecological cancers.Garrett A, Quinn MA.
Mercy Hospital for Women, Heidelberg, Victoria 3084, Australia. ***@****

Hormonal therapy has an established place in the management of women with gynaecological malignancies, including first-line therapy for recurrent receptor-positive endometrial cancer and low-grade stromal sarcoma. There is no place for adjuvant hormonal treatment of these cancers after primary surgery. Primary treatment with either oral or intra-uterine progestagens to preserve fertility in younger women with endometrial carcinoma is effective in about 70% of cases. Response rates to tamoxifen in advanced/recurrent ovarian cancers approximates 10%. To the authors' knowledge, no studies that reasonably compare different progestagens, different routes of therapy, different doses and different hormonal preparations have been published.



J Steroid Biochem Mol Biol. 2007 Aug-Sep;106(1-5):76-80. Epub 2007 May 24. Links
Aromatase inhibitors in gynecologic cancers.Krasner C.
Gillette Center for Women's Oncology, Massachusetts General Hospital, USA.

The female genital tract is hormonally responsive, and consequently some tumors, which arise within in it, may be treated at least in part, with hormonal manipulation. The range of responses in clinical trials and case reports will be reviewed. Many of these diseases are too rare for clinical trial testing, and in some cases evidence is anecdotal at best. Recurrences of ovarian cancer have been treated with tamoxifen and megesterol acetate with variable response rates from 0 to 56%. The favorable toxicity profile of aromatase inhibitors led to trials of these agents for the treatment of relapsed epithelial ovarian cancer. These agents have proved tolerable with minor response rates but a significant disease stabilization rate, which may be prolonged in a minority of cases. It is unclear if these responses may be predicted by estrogen receptor expression or aromatase expression. Anastrazole has also been tried in combination with an EGFR receptor-inhibitor, again showing minor responses but possibly an increase in TTT in some patients. Granulosa cell tumors of the ovary are rare, hormonally sensitive tumors, with reported responses to a variety of hormonal manipulations, including aromatase inhibition. In addition, combined endocrine blockade, including aromatase inhibition, has been tried with reports of success. Endometrial cancers, particularly type I lesions, are often treated with hormonal manipulation, most commonly with progestins, but also with antiestrogens such as tamoxifen. A trial of aromatase inhibition in the treatment of recurrent endometrial cancer showed minimal responses. Endometrial stromal sarcoma, an uncommon uterine malignancy, has shown response to hormonal treatments, with multiple case reports of efficacy of aromatase inhibition. Despite the rarity of some of these tumor types, rare tumor study groups, such as within the Gynecologic Oncology Group, should make an effort to prospectively define the utility of these treatments.