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Vaginal Estrogen Therapy for Patients with Breast Cancer.

ABSTRACT: On account of the good prognosis for patients with breast cancer, improving or maintaining the quality of life in the aftercare period is becoming more and more important. In particular, the increasing usage of aromatase inhibitors in the past few years has led to an increased incidence of vaginal atrophy with symptoms such as vaginal dryness, petechial bleeding, dyspareunia and recurrent cystitis. And just these symptoms have a detrimental impact on the quality of life of breast cancer patients. Application of a topical estrogen therapy represents the most effective means to treat vaginal atrophy. The use of a systemic or, respectively, topical hormone therapy is, however, contraindicated for breast cancer patients. Further clinical trials are needed in order to assess the safety of vaginal estrogen therapy.

SUBMITTER: Moegele M

PROVIDER: S-EPMC3862044 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Vaginal Estrogen Therapy for Patients with Breast Cancer.

Moegele M M Buchholz S S Seitz S S Lattrich C C Ortmann O O

Geburtshilfe und Frauenheilkunde 20131001 10

On account of the good prognosis for patients with breast cancer, improving or maintaining the quality of life in the aftercare period is becoming more and more important. In particular, the increasing usage of aromatase inhibitors in the past few years has led to an increased incidence of vaginal atrophy with symptoms such as vaginal dryness, petechial bleeding, dyspareunia and recurrent cystitis. And just these symptoms have a detrimental impact on the quality of life of breast cancer patients ...[more]

PMID: 24771890

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Project description:BackgroundAmong women, breast cancer is the leading cause of cancer-related death worldwide. Estrogen receptor α-positive (ERα+) breast cancer accounts for 70% of all breast cancer subtypes. Although ERα+ breast cancer initially responds to estrogen deprivation or blockade, the emergence of resistance compels the use of more aggressive therapies. While ERα is a driver in ERα+ breast cancer, ERβ plays an inhibitory role in several different cancer types. To date, the lack of highly selective ERβ agonists without ERα activity has limited the exploration of ERβ activation as a strategy for ERα+ breast cancer.MethodsWe measured the expression levels of ESR1 and ESR2 genes in immortalized mammary epithelial cells and different breast cancer cell lines. The viability of ERα+ breast cancer cell lines upon treatments with specific ERβ agonists, including OSU-ERb-12 and LY500307, was assessed. The specificity of the ERβ agonists, OSU-ERb-12 and LY500307, was confirmed by reporter assays. The effects of ERβ agonists on cell proliferation, cell cycle, apoptosis, colony formation, cell migration, and expression of tumor suppressor proteins were analyzed. The expression of ESR2 and genes containing ERE-AP1 composite response elements was examined in ERα+ human breast cancer samples to determine the correlation between ESR2 expression and overall survival and that of putative ESR2-regulated genes.ResultsIn this study, we demonstrate the efficacy of highly selective ERβ agonists in ERα+ breast cancer cell lines and drug-resistant derivatives. ERβ agonists blocked cell proliferation, migration, and colony formation and induced apoptosis and S and/or G2/M cell-cycle arrest of ERα+ breast cancer cell lines. Also, increases in the expression of the key tumor suppressors FOXO1 and FOXO3a were noted. Importantly, the strong synergy between ERβ agonists and ERα antagonists suggested that the efficacy of ERβ agonists is maximized by combination with ERα blockade. Lastly, ESR2 (ERβ gene) expression was negatively correlated with ESR1 (ERα gene) and CCND1 RNA expression in human metastatic ERα+/HER2- breast cancer samples.ConclusionOur results demonstrate that highly selective ERβ agonists attenuate the viability of ERα+ breast cancer cell lines in vitro and suggest that this therapeutic strategy merits further evaluation for ERα+ breast cancer.

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Vaginal Estrogen Therapy for Patients with Breast Cancer.

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Vaginal Estrogen Therapy for Patients with Breast Cancer.

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