Aromatase Inhibitor Therapy As Effective Rescue in a Patient With Tamoxifen-Refractory Metastatic Granulosa Cell Tumor of the Ovary

Lamm, Wolfgang; Schiefer, Ana Iris; Nöbauer, I.; Horvat, Reinhard; Speiser, Paul; Köstler, Wolfgang J.

doi:10.1200/jco.2013.49.5952

Cited by 12 publications

(8 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We did not see a similar response rate but did see a prolonged median duration of response of 13.8 months with importantly one patient maintaining a partial response at 4.5 years. Similar to other case reports, we demonstrated a complete response to letrozole in a patient who had failed tamoxifen demonstrating the possibility of effective rescue with changing hormonal agents [33].…”

Section: Non-surgical Treatment Options At Relapsesupporting

confidence: 81%

Stage I granulosa cell tumours: A management conundrum? Results of long-term follow up

Wilson

Fong

Mesnage

et al. 2015

Gynecologic Oncology

View full text Add to dashboard Cite

Section: Non-surgical Treatment Options At Relapsesupporting

confidence: 81%

Stage I granulosa cell tumours: A management conundrum? Results of long-term follow up

Wilson

Fong

Mesnage

et al. 2015

Gynecologic Oncology

View full text Add to dashboard Cite

“…In addition, hormonal therapies with aromatase inhibitors (AIs; anastrozole and letrozole) to decrease E2 synthesis can yield positive outcomes in patients with advanced or recurrent GCTs [13]. However, the effects of AIs are variable among patients, since some of them show little or no response [14]. This resistance may be attributable to the lack of ERs and/or of E2 in the patients, but screening of ER expression and determination of circulating E2 levels are not frequently performed prior to AI therapy.…”

Section: Introductionmentioning

confidence: 99%

Estradiol promotes cell survival and induces Greb1 expression in granulosa cell tumors of the ovary through an ERα‐dependent mechanism

Cluzet

Devillers

Petit

et al. 2022

The Journal of Pathology

View full text Add to dashboard Cite

Granulosa cell tumor (GCT) is a form of ovarian tumor characterized by its tendency to recur years after surgical ablation. Little is known about the mechanisms involved in GCT development and progression. GCTs can produce estradiol (E2), but whether this hormone could play a role in this cancer through its nuclear receptors, i.e. ERα and ERβ, remains unknown. Here, we addressed this issue by cell-based and molecular studies on human GCTs and GCT cell lines. Importantly, we observed that E2 significantly increased the growth of GCT cells by promoting cell survival. The use of selective agonists of each type of receptor, together with Esr1 (ERα) or Esr2 (ERβ)-deleted GCT cells, revealed that E2 mediated its effects through ERα-dependent genomic mechanisms and ERβ/ERα-dependent extra-nuclear mechanisms. Notably, the expression of Greb1, a prototypical ER target gene, was dose-dependently upregulated by E2 specifically through ERα in GCT cells. Accordingly, using GCTs from patients, we found that GREB1 mRNA abundance was positively correlated to intra-tumoral E2 concentrations. Tissue microarray analyses showed that there were various combinations of ER expression in primary and recurrent GCTs, and that ERα expression persisted only in combination with ERβ in $40% of recurrent tumors. Altogether, this study demonstrates that E2 can promote the progression of GCTs, with a clear dependence on ERα. In addition to demonstrating that GCTs can be classified as a hormone-related cancer, our results also highlight that the nature of ER forms present in recurrent GCTs could underlie the variable efficiency of endocrine therapies.

show abstract

“…AIs have also been used combined with other hormonal therapy: exemestane use was reported in one case as monotherapy and in combination with everolimus, emulating a strategy used in breast cancer. In this last instance, the patient experienced radiographic progression of disease after 2 months [48]. Evidence favoring AIs over other hormonal therapies in GCT is derived not only from the seemingly higher RR% but the more compelling rationale with our deeper understanding of GCT biology.…”

Section: Aromatase Inhibitorsmentioning

confidence: 99%

Ovarian Adult-Type Granulosa Cell Tumor: Focusing on Endocrine-Based Therapies

Yang¹,

Curtin²,

Muggia³

2018

Int. J. Endo. Oncol.

View full text Add to dashboard Cite

FOXL2 mutation is diagnostic, and, if pathology is in doubt, it should be performed.• Surgical resection and staging is key to assess prognosis.• Platinum-based adjuvant chemotherapy such as with carboplatin plus paclitaxel is a reasonable step for women diagnosed with distant recurrences or poor prognostic initial features. However, evidence for improved outcome is lacking. • Hormone-based therapies, especially with aromatase inhibitors, have shown activity and future studies may lead to further insight on the relationship of inhibition of hormonal pathways and tumor progression.Adult-typegranulosa cell tumors (GCTs), although rare, are the most commonly diagnosed neoplasms arising in the endocrine-active ovarian stroma. They are characterized by excessive production of estrogens, antimullerian hormone and inhibins. In 2009, a specific mutation in FOXL2 was identified to be pathognomonic of GCTs. How dysregulation of this transcription factor, resulting in upregulation of aromatase, leads to unchecked proliferation, and progression to a malignancy, remains unclear. The key pathological and clinical feature of GCTs that affects their usually favorable outcomes is a diagnosis of greater than Stage 1 disease at presentation. Chemotherapy is given as adjuvant upon an advanced stage diagnosis; however, its effect on survival upon recurrence is modest. On the other hand, aromatase inhibitors also lead to tumor regression and are suitable for long-term maintenance.

show abstract

Aromatase Inhibitor Therapy As Effective Rescue in a Patient With Tamoxifen-Refractory Metastatic Granulosa Cell Tumor of the Ovary

Cited by 12 publications

References 23 publications

Stage I granulosa cell tumours: A management conundrum? Results of long-term follow up

Stage I granulosa cell tumours: A management conundrum? Results of long-term follow up

Estradiol promotes cell survival and induces Greb1 expression in granulosa cell tumors of the ovary through an ERα‐dependent mechanism

Ovarian Adult-Type Granulosa Cell Tumor: Focusing on Endocrine-Based Therapies

Contact Info

Product

Resources

About