scholarly journals New therapeutic opportunities for low-grade serous ovarian cancer

2021 ◽  
Author(s):  
Tania Moujaber ◽  
Rosemary L Balleine ◽  
Bo Gao ◽  
Ida Madsen ◽  
Paul R Harnett ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Hormone Receptors ◽  
Residual Disease ◽  
Objective Response ◽  
Response Rates ◽  
Steroid Hormone Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Low Grade ◽  
Serous Ovarian Cancer ◽  
Platinum Based Chemotherapy

Low-grade serous ovarian cancer (LGSC) is a morphologically and molecularly distinct subtype of ovarian cancer, accounting for ~10% of serous carcinomas. Women typically present at a younger age and have a protracted clinical course compared with the more common, high-grade serous ovarian cancer. Currently, primary treatment of LGSC is the same as other epithelial ovarian cancer subtypes, with treatment for most patients comprised of debulking surgery and platinum/taxane chemotherapy. Primary surgical cytoreduction to no visible residual disease remains a key prognostic factor, however the use of platinum-based chemotherapy in both the upfront and relapsed setting, is being questioned due to low response rates in LGSC. Most LGSC express steroid hormone receptors and selected patients may benefit from endocrine maintenance therapy following chemotherapy, in particular those with evidence of residual disease at completion of surgery. In the recurrent setting, while hormonal therapies may offer disease stabilization with relatively low toxicity, objective response rates remain low. Strategies to increase response rates, including combining with CDK4/6 inhibitors, are being investigated. LGSC have a high prevalence of activating somatic mutations in mitogen-activated protein kinase pathway genes, most commonly in KRAS, BRAF and NRAS. Trametinib, a MEK inhibitor, has shown efficacy over chemotherapy and endocrine therapy. The use of combination targeted therapies, immunotherapy and anti-angiogenic agents, remain active areas of investigation for the treatment of LGSC.

scholarly journals Role of discoidin domain receptor 2 (DDR2) and microRNA-182 in survival of women with high-grade serous ovarian cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 101042831882398
Author(s):  
Susana Ramalho ◽  
Liliana AL De Angelo Andrade ◽  
Cássio Cardoso Filho ◽  
Rodrigo de Andrade Natal ◽  
Marina Pavanello ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Figo Stage ◽  
Stage I ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Discoidin Domain Receptor ◽  
Post Surgery ◽  
Platinum Based Chemotherapy ◽  
Discoidin Domain Receptor 2

The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II – versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II – versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p < 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.

Steroid hormone receptors and carcinoma of the breast

1982 ◽  
Vol 243 (2) ◽  
pp. E99-E102 ◽  
Author(s):  
W. L. McGuire ◽  
C. K. Osborne ◽  
G. M. Clark ◽  
W. A. Knight
Keyword(s):  
Primary Tumor ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Objective Response ◽  
Response Rates ◽  
Prognostic Indicator ◽  
Steroid Hormone Receptors ◽  
Hormone Dependence ◽  
Carcinoma Of The Breast ◽  
Subsequent Relapse

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50-60% are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of subsequent relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of ER and assay of progesterone receptor (PgR) are useful for increasing the accuracy of selecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be the best available tumor marker of hormone dependence.

scholarly journals Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1917 ◽  
Author(s):  
Changwon Yang ◽  
Hee Seung Kim ◽  
Soo Jin Park ◽  
Eun Ji Lee ◽  
Se Ik Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Target Genes ◽  
Apoptotic Cell ◽  
Serous Cystadenoma ◽  
Low Grade ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Potential Biomarker ◽  
Platinum Based Chemotherapy

In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that candidate miRNAs might regulate in patient tissues. miR-214-3p was highly expressed in tissues and exosomes derived from EOC with high malignancy and also found to regulate the expression of LIM homeobox domain 6 (LHX6) mRNA. Serum exosomal levels of miR-214-3p were significantly increased in platinum-resistant HGSO (25.2-fold, p < 0.001) compared to the exosomal expression of benign tumor patients. On transfection of miR-214-3p inhibitor in EOC cells, cell proliferation was inhibited while apoptotic cell death was increased. Collectively, we suggest that miR-214-3p in serum exosomes can be a potential biomarker for the diagnosis and prognosis of ovarian tumor, and its inhibition can be a supportive treatment for EOC.

The Life and Times of Low-Grade Serous Carcinoma of the Ovary

2013 ◽  
pp. e195-e199
Author(s):  
David M. Gershenson
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Mapk Pathway ◽  
Gynecologic Oncology ◽  
Mitogen Activated Protein Kinase ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Major Advance ◽  
The Past ◽  
Platinum Based Chemotherapy

For the past several years, all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance, leading to separate clinical trials for patients with this subtype, originating from the Gynecologic Oncology Group's Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20% to 40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare—approximately 5%. In genomic profiling studies, these tumors appear to cluster with serous tumors of low malignant potential. Compared with high-grade serous carcinomas, low-grade serous carcinomas are also characterized by a low frequency of p53 mutations, greater expression of ER and PR, and greater expression of PAX2 and IGF-1. Primary treatment of low-grade serous carcinoma includes surgery plus platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonged overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormone therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations.

Effect of estrogen and progesterone receptor expression on progression-free and overall survival outcomes in low-grade serous ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5560-5560
Author(s):  
Marta Llaurado Fernandez ◽  
Amy Dawson ◽  
Hannah Kim ◽  
Nicole Lam ◽  
Maegan Bruce ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Receptor Expression ◽  
Endocrine Treatment ◽  
Survival Outcomes ◽  
P Value ◽  
Low Grade ◽  
Serous Ovarian Cancer ◽  
Allred Score ◽  
Platinum Based Chemotherapy

5560 Background: Research on ER/PR receptor function in low-grade serous ovarian cancer (LGSC) and the determinants of response to treatment are lacking. A recent study (Sehouli et al.,2018) described ER/PR immunohistochemistry (IHC) cut-points that distinguished PFS. Thus, we report on a group of patients with ER/PR expression by IHC in tumor samples of patients with LGSC and used this information to evaluate survival outcomes. Methods: Clinical information and FFPE sections were obtained from the Canadian Ovarian Experimental Unified Resource (COEUR). Tissue microarray (TMA) sections were stained for ER/PR using standard IHC techniques (MK). 50 stage 3 and 5 stage 4 patients were analyzed. ER/PR expression was scored using a simple scoring system ( < 1% cells staining, 1-50%, and ≥ 50%) and Allred scoring. We compared Kaplan-Meier (KM) survival (PFS and OS) curves using Log rank testing and Cox regression was used to model predictive/prognostic factors. A p-value of 0.05 was considered significant. Results: The mean age of the population was 49.5 years (SD;13.7). Ninety percent of patients were treated by surgery followed by platinum-based chemotherapy (PBC). Simple scoring did not discriminate outcomes as well for ER levels. PR Allred score ( < 2, vs 2- < 6 vs ≥6) clearly discriminated KM curves for PFS (p = 0.036) and OS (p = 0.01). For Allred ER score ( < 7 vs.7- < 8 vs 8) did not distinguish PFS (p = 0.4) but notably most patients received PBC after surgery. ER Allred score significantly distinguished OS (p = 0.008). Significant factors on Cox regression for PFS were residuum (p = 0.008;95%CI:1.2-3.1) and PR (p = 0.05;95%CI:0.39-0.99), whereas for OS ER(p = 0.01:95%CI:0.2-0.8) and residuum (p = 0.04;95%CI:1-2.8). Conclusions: ER/PR expression by Allred scoring was associated with PFS and OS. Patients will benefit from much needed research on ER/PR prediction/prognosis in LGSC. This work can inform clinical trials selection/stratification and patient selection for endocrine treatment.

scholarly journals Expression of estrogen-related receptors in ovarian cancer and impact on survival

2021 ◽  
Author(s):  
Susanne Schüler-Toprak ◽  
Florian Weber ◽  
Maciej Skrzypczak ◽  
Olaf Ortmann ◽  
Oliver Treeck
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Hormone Receptors ◽  
Progression Free Survival ◽  
Steroid Hormone Receptors ◽  
Serous Ovarian Cancer ◽  
Survival Analyses ◽  
Independent Prognostic Marker ◽  
Ovarian Cancers ◽  
Impact On Survival

Abstract Purpose This study further approaches the role of estrogen-related receptors (ERRs) in ovarian cancer. Protein expression of ERRα, ERRβ and ERRγ in ovarian cancer was assessed and was correlated with ovarian cancer markers, steroid hormone receptors and cancer-associated genes. Additionally, we examined to what extent expression of ERRs affects survival of ovarian cancer patients. Methods For this purpose, we established a tissue microarray from 208 ovarian cancer patients and performed immunohistochemical analyses of the mentioned proteins. Results ERRα and ERRγ protein could be detected at different levels in more than 90% of all ovarian cancer tissues, whereas expression of ERRβ was observed in 82.2% of the cases. ERRα was found to positively correlate with ovarian cancer marker CEA (p < 0.005) and ERRγ correlated with ERα (p < 0.001). Univariate survival analyses revealed that ERRα expression did not affect overall (OS) or progression-free survival (PFS) of ovarian cancer patients. In contrast, higher expression of ERRβ in serous ovarian cancers was found to lead to a significantly decreased OS (p < 0.05). The strongest impact on survival was exhibited by ERRγ. Lower expression of this receptor in women with serous ovarian cancers indicated significantly increased OS compared to those with higher levels of ERRγ (p < 0.05). Multivariate survival analyses revealed ERRγ as an independent prognostic marker regarding OS of patients with serous ovarian cancer. Conclusion Our data demonstrating that ERR proteins are frequently expressed in ovarian cancer and high levels of ERRβ and ERRγ significantly decreased OS of serous ovarian cancer patients suggest that these proteins might be interesting therapy targets in this cancer entity.

scholarly journals A therapeutic approach to low-grade serous ovarian carcinoma

2020 ◽  
Vol 48 (2-3) ◽  
pp. 109-115
Author(s):  
Branka Petrić-Miše ◽  
◽  
Dinka Šundov
Keyword(s):  
Ovarian Cancer ◽  
Endocrine Therapy ◽  
Gene Mutations ◽  
Mitogen Activated Protein Kinase ◽  
Low Grade ◽  
Serous Ovarian Cancer ◽  
Cyclin Dependent Kinase ◽  
Strong Recommendation ◽  
Mitogen Activated Protein ◽  
Stage Ia

Low-grade serous ovarian cancer (LGSOC) has less aggressive behavior and a better clinical outcome than high-grade serous ovarian cancer (HGSOC). Considering that this malignancy is relatively chemoresistant, surgery is the keystone of treatment, with a strong recommendation for maximal cytoreduction. Women with stage IA-IB disease should undergo observation alone after primary cytoreductive surgery. In contrast, observation, chemotherapy, or endocrine therapy are possible options for those with stage IC-IIA disease. Patients with stage IIB-IV disease receive either chemotherapy with carboplatin and paclitaxel for six cycles followed by endocrine therapy, most commonly with aromatase inhibitors, or endocrine therapy alone until disease progression or unacceptable toxicity. Surgery, chemotherapy, and endocrine therapy are also used in patients with recurrent disease. Targeted agents, especially mitogen-activated protein kinase (MEK) inhibitors and cyclin-dependent kinase (CDK) inhibitors, are currently under evaluation in this clinical setting. Additional research on the genomics of LGSOC to better define the activating gene mutations involved in the carcinogenesis is strongly warranted to improve the prognosis with this malignancy.

scholarly journals Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

2020 ◽  
Vol 38 (30) ◽  
pp. 3528-3537
Author(s):  
Paul DiSilvestro ◽  
Nicoletta Colombo ◽  
Giovanni Scambia ◽  
Byoung-Gie Kim ◽  
Ana Oaknin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Newly Diagnosed ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Interval Surgery

PURPOSE In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed BRCA1- and/or BRCA2-mutated advanced ovarian cancer compared with placebo (hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41; median not reached v 13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors. PATIENTS AND METHODS Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete [CR] or partial response [PR]), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status ( BRCA1 or BRCA2). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate. RESULTS The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a BRCA1 or BRCA2 mutation, respectively. CONCLUSION Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.

Sign in / Sign up

Export Citation Format

Share Document