Emerging Concepts-Advanced Ovarian, Fallopian, Peritoneal, and Cervical Cancers - Episode 1

Introduction: Molecular Testing in Ovarian Cancer

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Ovarian cancer is comprised of several histologic subtypes, including serous, which is the most common subtype, clear cell, endometrioid, and mucinous, which are rare and unresponsive to chemotherapy, explains Bradley J. Monk, MD. These histologies are further classified as Type I or II based on whether or not they display high-grade characteristics related to clinicopathologic or molecular features.

Low-grade serous tumors in the fallopian tubes, peritoneal, and ovaries, have molecular perturbations in the mitogen-activated protein (MAP) kinase pathway, while high-grade tumors are characterized by p53 mutations, says Monk. Diving even deeper, based on the entire genome, there are multiple subtypes within each subtype, representing a very heterogeneous disease, notes Robert L. Coleman, MD.

High-grade tumors can be bifurcated based on the BRCA gene alterations or genes related to BRCA. Newer data show that women with non-serous cancers also express a high prevalence of BRCA1 mutations and other homologous recombination defects, notes Angeles Alvarez Secord, MD. The National Comprehensive Cancer Network currently recommends that women, regardless of family history, age of onset, and histologic subtype, should be tested for BRCA.

There are 2 distinct reasons to test for a genetic mutation, says Secord; one reason is to determine hereditary predisposition through panel testing, and the other is to help guide targeted therapy by testing the tumor itself. Other than BRCA, a specific driver mutation has not yet been identified in ovarian cancer. For predicting response to PARP inhibition, studies have shown that a panel of genes involved in homologous repair deficiency could also effectively predict outcomes; however, more research is needed.