Having all the information is even more crucial as we aim to offer our patients hope." Without this test, we do not have all the information for informed decision-making with regards to devising a comprehensive treatment plan for our patients. “This puts into perspective the importance of HRD genomic instability testing. Knowing that roughly half of our patients are HRD-positive, this testing can identify important information about their tumor which may better inform their treatment plan than testing for a BRCA mutation alone – which is present in approximately just 25% of women with the disease,” said Dr. “In today’s treatment landscape, where cancer therapy is becoming increasingly personalized and biomarker-based, every woman diagnosed with advanced ovarian cancer should receive HRD genomic instability testing. HRD-positive tumors are identified via detection of certain mutations that signal the presence of HRD, such as BRCA1/2 mutations and markers of genomic instability (including loss of heterozygosity (LOH)).
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“This conversation can also serve as a way to discuss the full treatment path ahead and set expectations for what’s to come during different phases of their treatment journey.” I use it as an opportunity to share what it may mean for their care,” said Dr. When I see a patient is HRD-positive, I make sure they understand the results. “Advanced ovarian cancer is a tough disease. 10 Given the relationship between HRD-positivity and PARP inhibitor regimens, HRD genomic instability testing is an important component of advanced ovarian cancer management. 9 Due to the increased sensitivity of HRD-positive tumors to PARP inhibition, PARP inhibitor-based regimens in tumors with HRD may drive tumor cell death. HRD is the functional impairment in a key DNA damage repair pathway that hinders a cell from fixing damaged DNA. Women with HRD-positive disease account for approximately 50 percent of the advanced ovarian cancer population. 6 Research has demonstrated that HRD is associated with an increased sensitivity to PARP inhibition.
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Identifying the Right Patients for Personalized Medicine The introduction of PARP inhibitors for the treatment of certain women with advanced ovarian cancer is one recent example of how personalized medicine is transforming the way the disease is treated. “I don’t think we have ever seen so many options to help improve clinical outcomes in the modern management of ovarian cancer.” “The treatment landscape for advanced ovarian cancer has evolved from where it was ten years ago, when at that stage it was very much a standard approach of surgery, chemotherapy, and then watch and wait – to one where patients receive individualized care based on the unique features of their cancer,” said Warner Huh, MD, FACOG, FACS, chair of the Department of Obstetrics and Gynecology at the University of Alabama at Birmingham School of Medicine. This shift started with the introduction of germline testing for inherited BRCA mutations, but new advances in comprehensive biomarker testing – including testing for homologous recombination deficiency (HRD) genomic instability – are continuing to usher in this change. However, change is on the horizon with the advent of precision medicine in advanced ovarian cancer. 1 The majority of women are diagnosed at the advanced stages of the disease, and about 70 percent will relapse within three years after receiving primary surgery and first-line platinum-based chemotherapy. In 2021, approximately 21,000 women in the US will be diagnosed with ovarian cancer, and nearly 14,000 will die from the disease.