Hormone therapy in epithelial ovarian cancer.

Makar, Amin

doi:10.1677/erc.0.0070085

Cited by 59 publications

(48 citation statements)

References 71 publications

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“…Monotherapy studies using tamoxifen, aromatase inhibitors, and GnRH analogues had yielded variable results with objective response rates ranging between 0 and 56%. 17,[19][20][21][34][35][36][37][38] Combinatorial treatment regimens combining tamoxifen and goserelin or tamoxifen and Gefitinib had obtained results with objective response rates of up to 11.5%. 39,40 Few of these studies had selected patients based on the immunohistochemically determined estrogen receptor status.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, concerning tamoxifen, it has not been definitely clarified whether it only acts as a pure estrogen antagonist in ovarian tissue, or it has also an agonist effects. [17][18][19][20][21] In breast cancer, we had recently described estrogen receptor-a (ESR1) gene amplification as a frequent mechanism for estrogen receptor overexpression. More than 20% of breast cancers showed ESR1 gene amplification and more than 15% additional cases low-level ESR1 gene copy number gains.…”

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Estrogen receptor gene amplification occurs rarely in ovarian cancer

et al. 2009

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Amplification of the gene encoding estrogen receptor-a occurs in about 20% of breast cancers and is an important mechanism for estrogen receptor overexpression in this tumor type. In ovarian cancer, overexpression of estrogen receptor protein has been described in more than two thirds of cases. To study a potential role of estrogen receptor-a gene amplification for estrogen receptor overexpression in ovarian cancer, a tumor tissue microarray containing 428 ovarian cancers was analyzed by fluorescence in situ hybridization for estrogen receptor-a gene amplification and immunohistochemistry for estrogen receptor expression. The estrogen receptor-a gene status was successfully determined in 243 of 428 arrayed cancers. Estrogen receptor gene amplification was found in 5 of 243 (2%) of tumors. Amplification levels were usually low, with 4-8 estrogen receptor-a gene copies. However, one case had a high-level amplification, with more than 30 estrogen receptor-a gene copies. Keywords: ovarian cancers; estrogen receptor-a gene; estrogen receptors; fluorescence in situ hybridization; immunohistochemistry Worldwide, ovarian cancer is the fifth most frequent malignant tumor in women and the most common cause of death among cancers of the reproductive system.1 Prognosis is generally poor as these cancers are often detected in late stage. The median overall survival in these patients is 24-38 months after diagnosis. 2Treatment options include surgical removal of the tumor mass with a maximal reduction of the peritoneal cancer mass in case of local tumor extension. In addition, topical and systemic cytotoxic therapy is applied. Ovarian cancer belongs to the group of cancers with frequent expression of steroid hormone receptors. Depending on the study estrogen receptor expression has been reported in 25-86% of ovarian cancers with the highest percentages reported in endometroid and serous subtypes.3-16 Accordingly, endocrine therapy is a recognized option in the treatment of chemoresistant ovarian cancer after the failure of first-and second-line therapies. However, not all estrogen receptor-positive ovarian cancers respond to antiestrogen therapy, and it was suggested that it might be because of the facts that most of the studies have been retrospective, small in size without adequate selection of the patients and generally used hormonal therapy as a last-line therapy for the refractory or resistant ovarian cancers. Moreover, concerning tamoxifen, it has not been definitely clarified whether it only acts as a pure estrogen antagonist in ovarian tissue, or it has also an agonist effects. 17-21In breast cancer, we had recently described estrogen receptor-a (ESR1) gene amplification as a frequent mechanism for estrogen receptor overexpression. More than 20% of breast cancers showed ESR1 gene amplification and more than 15% additional cases low-level ESR1 gene copy number gains.22 Preliminary data also suggested that ESR1 amplified breast cancers may exhibit a high responsiveness to tamoxifen. To determine, whether ESR1 amplificat...

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Section: Discussionmentioning

confidence: 99%

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Estrogen receptor gene amplification occurs rarely in ovarian cancer

et al. 2009

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“…Despite the expression of ER in approximately 60% of epithelial ovarian cancers (Havrilesky et al, 2001;Rao and Slotman, 1991), only 5 ± 18% women clinically respond to the antiestrogen tamoxifen (Hatch et al, 1991;Ahlgren et al, 1993;Makar, 2000). However, most studies are retrospective and have been designed as second line therapy of resistant or recurrent disease after chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Katsaros²,

et al. 2002

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Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of ®bulin-1 mRNA results in four di erent variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of ®bulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, ®bulin-1C and -1D are the predominant forms, whereas ®bulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coampli®cation of ®bulin-1C and -1D to study the relative expression of these ®bulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the ®bulin-1C:1D and ®bulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, ®bulin-1C mRNA was induced by estradiol in a dose-and time-dependent manner. Since others and we have previously shown an increased expression of ERa as compared to ERb in ovarian cancer cells, we investigated whether ERa or ERb is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and ®bulin-1, was infected with recombinant ERa or ERb encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERa-but not ERb-infected cells, suggesting that ®bulin-1C induction is mediated through ERa. In ovarian tumors, a trend towards a correlation between ®bulin-1C and ERa expression levels was noted. In conclusion, this study showed an increased ®bulin-1C: -1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This ®nding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERa promoted ovarian tumor progression.

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“…The results of experimental and clinical studies suggest a role of estrogens in ovarian carcinogenesis (Rao and Slotman, 1991;Makar, 2000). A recent prospective cohort study involving 211 000 postmenopausal women showed an increased risk of ovarian cancer mortality in women who used estrogen replacement therapy for 10 or more years (Rodriguez et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Moll

Katsaros²,

Lazennec

et al. 2002

Oncogene

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Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of ®bulin-1 mRNA results in four dierent variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of ®bulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, ®bulin-1C and -1D are the predominant forms, whereas ®bulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coampli®cation of ®bulin-1C and -1D to study the relative expression of these ®bulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the ®bulin-1C:1D and ®bulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, ®bulin-1C mRNA was induced by estradiol in a dose-and time-dependent manner. Since others and we have previously shown an increased expression of ERa as compared to ERb in ovarian cancer cells, we investigated whether ERa or ERb is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and ®bulin-1, was infected with recombinant ERa or ERb encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERa-but not ERb-infected cells, suggesting that ®bulin-1C induction is mediated through ERa. In ovarian tumors, a trend towards a correlation between ®bulin-1C and ERa expression levels was noted. In conclusion, this study showed an increased ®bulin-1C: -1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This ®nding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERa promoted ovarian tumor progression.

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Hormone therapy in epithelial ovarian cancer.

Cited by 59 publications

References 71 publications

Estrogen receptor gene amplification occurs rarely in ovarian cancer

Estrogen receptor gene amplification occurs rarely in ovarian cancer

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

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