paywalled - Outcomes of Primary Surgical Cytoreduction in Patients with BRCA-associated High-grade Serous Ovarian Carcinoma

 Outcomes of Primary Surgical Cytoreduction in Patients with BRCA-associated High-grade Serous Ovarian Carcinoma

Objective

BRCA-associated and sporadic ovarian cancers have different pathologic and clinical features. Our goal was to determine if BRCA mutation status is an independent predictor of residual tumor volume following primary surgical cytoreduction.

Highlights

► Differences in the biology of BRCA-associated and sporadic ovarian cancers do not result in differences in primary surgical outcomes.
► The improved survival of BRCA-associated ovarian cancers is not confounded by differences in primary surgical outcome.

(in research - genome) Integrated Analysis of Gene Expression and Tumor Nuclear Image Profiles Associated with Chemotherapy Response in Serous Ovarian Carcinoma

Integrated Analysis of Gene Expression and Tumor Nuclear Image Profiles Associated with Chemotherapy Response in Serous Ovarian Carcinoma
 

Background
Small sample sizes used in previous studies result in a lack of overlap between the reported gene signatures for prediction of chemotherapy response. Although morphologic features, especially tumor nuclear morphology, are important for cancer grading, little research has been reported on quantitatively correlating cellular morphology with chemotherapy response, especially in a large data set. In this study, we have used a large population of patients to identify molecular and morphologic signatures associated with chemotherapy response in serous ovarian carcinoma.

abstract: Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

Abstract

Purpose: 

This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. 

Experimental Design: 

We applied a customized TaqMan Low Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. 

Results: 

Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (P=0.06), four covariates (age, stage, CA125 level and surgical debulking) do (P=0.03). 

When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in overall survival prediction (log-rank statistic P less than 0.003). The predictive power of this 11-gene signature was confirmed by dividing high and low risk patient groups, as defined by their clinical covariates, into four specific risk groups based on expression levels. 

Conclusion: 

This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer.

Marker of DNA Damage Could Predict Response to Platinum Chemotherapy

Marker of DNA Damage Could Predict Response to Platinum Chemotherapy:

• Assay could direct treatment options for triple-negative breast cancer.
• Accumulations of telomere AI predicted sensitivity to therapy.

PHILADELPHIA — Scientists have uncovered a marker of DNA damage that could predict who will respond to platinum-based chemotherapy drugs like cisplatin or carboplatin.
These drugs are widely used for ovarian cancer, but as with most cancer drugs, it can be difficult to predict who will respond to therapy.
A team of researchers from the Dana-Farber Cancer Institute found that this marker, telomeric allelic imbalance or tAI, could predict sensitivity to therapy in patients with triple-negative breast cancer.
The results are published in Cancer Discovery, a journal of the American Association for Cancer Research.
“We currently do not have any targeted therapies for patients with triple-negative breast cancer, so if these laboratory findings are confirmed and an assay is created to predict sensitivity to drugs that target defective DNA repair, it would be a major step forward,” said lead pathologist Andrea Richardson, M.D., Ph.D., assistant professor of medicine at Dana-Farber Cancer Institute.
Scientists have long known that DNA repair status is a predictor of sensitivity to therapy and thus prognosis. However, measurements of DNA repair status have been slow to arrive.
Richardson and colleagues looked for genomic signatures in cell lines and tumors and correlated them to platinum sensitivity.
In patients with triple-negative breast cancer, they found that a high level of subchromosomal regions with allelic imbalance extended to the telomere predicted response to cisplatin treatment. The same was true for serous ovarian cancer.
Importantly for patients with triple-negative breast cancer, researchers found an inverse relationship between the level of tAI and BRCA1 expression.