Endocrine therapy in epithelial ovarian cancer

Langdon, Simon P.; Gourley, Charlie; Gabra, Hani; Stanley, Bárbara

doi:10.1080/14737140.2017.1272414

Cited by 42 publications

(36 citation statements)

References 72 publications

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“…In ovarian cancer samples, androstenedione can be formed from DHEA (Chura et al, 2009a), although Ren et al (Ren et al, 2015) found no evidence for further formation of estrogens via the aromatase pathway or activation of androstenedione to testosterone and 5α-dihydrotestosterone, as also supported by down-regulation of AKR1C3 . However, in other studies, CYP19A1 was expressed in stroma cells of ovarian cancers (Manna et al, 2016), and has been considered a target for an endocrine therapy (Langdon et al, 2017). …”

Section: Disturbed Transport and Estrogen Actions In Gynecological Camentioning

confidence: 98%

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

2017

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Endometrial and ovarian cancers predominately affect women after menopause, and are more frequently observed in developed countries. These are considered to be hormone-dependent cancers, as steroid hormones, and estrogens in particular, have roles in their onset and progression. After the production of estrogens in the ovary has ceased, estrogen synthesis occurs in peripheral tissues. This depends on the cellular uptake of estrone-sulfate and dehydroepiandrosterone-sulfate, as the most important steroid precursors in the plasma of postmenopausal women. The uptake through transporter proteins, such as those of the organic anion-transporting polypeptide (OATP) and organic anion-transporter (OAT) families, is followed by the synthesis and action of estradiol E2. Here, we provide an overview of the current understanding of this intracrine action of steroid hormones, which depends on the availability of the steroid precursors and transmembrane transporters for precursor uptake, along with the enzymes for the synthesis of E2. The data is also provided relating to the selected transmembrane transporters from the OATP, OAT, SLC51, and ABC-transporter families, and the enzymes involved in the E2-generating pathways in cancers of the endometrium and ovary. Finally, we discuss these transporters and enzymes as potential drug targets.Keywords: sulfatase, aromatase, 17beta-hydroxysteroid dehydrogenase, transporters, OATP, ABC-transporter HORMONE-DEPENDENT CANCERSSteroid hormones have important roles in human physiology, and the disruption of androgen, estrogen, and progesterone actions are implicated in the development of hormone-dependent cancers and benign hormone-dependent diseases. Hormone-dependent cancers include prostate, breast, endometrial, and ovarian cancers, which comprise more than 20% of all cancers in humans, and more than 35% of cancers in women (Ferlay et al., 2013). Indeed, in women, breast cancer is the most frequent cancer in the developed world. In 2012, 1,671,149 new cases of breast cancer were estimated worldwide, with 521,907 associated deaths. In the developed world, endometrial cancer is the most common among gynecological cancers. Worldwide, there were 319,605 new cases and 76,160 deaths from endometrial cancer in 2012 alone (Ferlay et al., 2013). The most deadly of the hormone-dependent cancers is ovarian cancer. Worldwide, there were 238,719 new cases and 151,905 deaths from ovarian cancer in 2012 (Ferlay et al., 2013).

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Section: Disturbed Transport and Estrogen Actions In Gynecological Camentioning

confidence: 98%

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

2017

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“…However, the clinical activity of endocrine therapy in ovarian cancer has been disappointing, with response rates reminiscent of many tested therapeutic agents that have been deemed inactive . Small phase 2 studies have shown response rates of the AI letrozole in recurrent ovarian cancer to be 0%‐15% (Table ) . Despite low response rates to aromatase inhibition, clinical benefit rates (responses plus stable disease) of letrozole are estimated to be as high as 56% with duration of disease stability of 9.6 months .…”

Section: Use Of Endocrine Therapy In the Treatment Of Ovarian Cancer?mentioning

confidence: 99%

“…[87][88][89] Small phase 2 studies have shown response rates of the AI letrozole in recurrent ovarian cancer to be 0%-15% (Table 3). 88,90 Despite low response rates to aromatase inhibition, clinical benefit rates (responses plus stable disease) of letrozole are estimated to be as high as 56% with duration of disease stability of 9.6 months. 91 Several clinical trials of the SERM tamoxifen (Table 3) have demonstrated an overall 10%-13% objective response rate and a 32%-35% disease stabilization rate.…”

Section: Use Of Endocrine Therapy In the Treatment Of Ovarian Cancer?mentioning

confidence: 99%

The role of menopausal hormone therapy in women with or at risk of ovarian and breast cancers: Misconceptions and current directions

Temkin

Mallen

Bellavance

et al. 2018

Cancer

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For women who are candidates for menopausal hormone therapy (MHT), estrogen can provide relief from symptomatic menopause, decrease rates of chronic illnesses, and improve health‐related quality of life. However, confusion surrounds the evidence regarding the impact of exogenous estrogen and progesterone on the breast and ovary. Available data regarding the risks of MHT (estrogen and/or progestin) related to the development of breast and ovarian cancer are often inconsistent or incomplete. Modern molecular and genetic techniques have improved our understanding of the heterogeneity of breast and ovarian cancer. This enhanced understanding of the disease has impacted our understanding of carcinogenesis. Treatment options have evolved to be more targeted toward hormonal therapy for certain subtypes of disease, whereas cytotoxic chemotherapy remains the standard for other histological and molecular subtypes. The role of MHT in the breast and ovarian cancer survivor, as well as women who are at high risk for the development of hereditary breast and ovarian cancer, remains controversial despite evidence that this treatment can improve quality of life and survival outcomes. Through this article, we examine the evidence for and against the use of MHT with a focus on women who have or are at high risk for breast and ovarian cancer.

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“…Despite numerous published clinical studies on the effectiveness and safety of ET in EOC during the past decades the role of ET in EOC is not well defined [4][5][6][7][8][9][10]. We do not know which hormonal agent is most effective nor the optimal setting.…”

Section: Introductionmentioning

confidence: 99%

“…histological subtypes) and includes mainly heavily pretreated patients. Despite the low evidence for efficacy, ET is an attractive treatment option, and included in many international guidelines for heavily pretreated patients, since it is associated with an often-favourable safety profile, easy intake and low cost [5,7,[9][10][11]15]. Patient preference is important in the decision-making process of choosing best treatment, especially at late relapse, but must be based on thorough physician-patient communication including information regarding prognosis and treatment alternatives.…”

Section: Introductionmentioning

confidence: 99%

Pattern of endocrine treatment for epithelial ovarian cancer in the Southeast medical region of Sweden: a population-based study

et al. 2019

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Aim of the study: Endocrine treatment (ET) is an alternative as salvage therapy in epithelial ovarian cancer (EOC) but the usage in routine care is unknown. We evaluated the treatment patterns and outcome of patients receiving ET for EOC in the Southeast medical region in Sweden. Method: Patients were identified through the population-based Southeast Quality Registry for gynaecological cancer. Inclusion criteria were: age 18 years, histologically verified EOC diagnosed 2000-2013, ET for 4 weeks. Coverage compared with the Swedish National Cancer Registry was 100%. Data extracted from medical records was collected by means of a study-specific Case Report Form. Last date of follow-up was February 1st, 2018. All statistics were descriptive. Results: Altogether 248 (18%) of 1414 patients were treated with ET. Most (49%) had received only one, and 34% two previous lines of chemotherapy. Time from last chemotherapy to ET was 4 months, range 0-55months. The reason for initiating ET was tumor progression (66%), chemotherapy related toxicity (29%) and maintenance (4%). Tamoxifen was prescribed in 94% of cases. Best response was partial (< 5%) and stable disease (50%). No patient had a complete response. 194 (78%) patients received subsequent chemotherapy, of these 27% had 3-7 lines of chemotherapy. Duration of ET was a median 4 months (range 1-80 months). Median time from ET to subsequent chemotherapy was 5 months (range 0-79). The median overall survival was 45 months (range 9-173). Conclusion: In the Southeast region of Sweden, endocrine treatment for EOC was prescribed inconsistently and in various settings, usually initiated by a rising CA-125 level. Poorer documentation and irregular tumor response assessment were observed for endocrine treatment compared to chemotherapy. ARTICLE HISTORY

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Endocrine therapy in epithelial ovarian cancer

Cited by 42 publications

References 72 publications

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

The role of menopausal hormone therapy in women with or at risk of ovarian and breast cancers: Misconceptions and current directions

Pattern of endocrine treatment for epithelial ovarian cancer in the Southeast medical region of Sweden: a population-based study

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