A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission

Levine, Douglas A.; Park, Kay J.; Juretzka, Margrit M.; Esch, Julie; Hensley, Martee L.; Aghajanian, Carol; Lewin, Sharyn N.; Konner, Jason; Derosa, F.; Spriggs, David R.; Iasonos, Alexia; Sabbatini, Paul

doi:10.1002/cncr.23072

Cited by 46 publications

(34 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

Estrogen receptor gene amplification occurs rarely in ovarian cancer

et al. 2009

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen receptor gene amplification occurs rarely in ovarian cancer

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Other hormonal agents that have been evaluated in this context are progesterone receptor agonists (Ho 2003, Niwa et al 2008, Diep et al 2013 and antiandrogens, including flutamide and bicalutamide (Levine et al 2007).…”

Section: Endocrine Treatment Approachesmentioning

confidence: 99%

The role of reproductive hormones in epithelial ovarian carcinogenesis

Gharwan

Bunch

Annunziata

2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

Epithelial ovarian cancer comprises w85% of all ovarian cancer cases. Despite acceptance regarding the influence of reproductive hormones on ovarian cancer risk and considerable advances in the understanding of epithelial ovarian carcinogenesis on a molecular level, complete understanding of the biologic processes underlying malignant transformation of ovarian surface epithelium is lacking. Various hypotheses have been proposed over the past several decades to explain the etiology of the disease. The role of reproductive hormones in epithelial ovarian carcinogenesis remains a key topic of research. Primary questions in the field of ovarian cancer biology center on its developmental cell of origin, the positive and negative effects of each class of hormones on ovarian cancer initiation and progression, and the role of the immune system in the ovarian cancer microenvironment. The development of the female reproductive tract is dictated by the hormonal milieu during embryogenesis. Intensive research efforts have revealed that ovarian cancer is a heterogenous disease that may develop from multiple extra-ovarian tissues, including both Mü llerian (fallopian tubes, endometrium) and non-Mü llerian structures (gastrointestinal tissue), contributing to its heterogeneity and distinct histologic subtypes. The mechanism underlying ovarian localization, however, remains unclear. Here, we discuss the role of reproductive hormones in influencing the immune system and tipping the balance against or in favor of developing ovarian cancer. We comment on animal models that are critical for experimentally validating existing hypotheses in key areas of endocrine research and useful for preclinical drug development. Finally, we address emerging therapeutic trends directed against ovarian cancer.

show abstract

“…In women with epithelial ovarian cancer, researchers have reported an association between short poly-glutamine tracts in the AR and decreased progressionfree and overall survival [58]. These associations ultimately led to the evaluation of anti-androgen therapy in two clinical trials, neither of which demonstrated significant improvement in progression-free or overall survival [59,60]. Unfortunately, these trials were performed in heavily treated women with refractory disease leaving the efficacy of an anti-androgen as first-line therapy an open question.…”

Section: Epithelial Ovarian Cancermentioning

confidence: 99%