How Does Homologous Recombination Deficiency Affect Ovarian Cancer?
- HRD is a genetic factor that is sometimes present in women with BRCA gene mutations but can be present in other women as well.
- It affects the cancer cells’ ability to repair their DNA.
- Knowing whether a woman has HRD can inform the type of treatment she receives.
HRD Explained
Homologous recombination deficiency, or HRD, is a genetic factor in which cells have difficulty repairing themselves. These cells can then become cancerous. The reverse is also true: Genetic mutations in cancer can also cause HRD.
Read MoreThis deficiency is sometimes present in women who have mutations in the BRCA gene, the gene mutation most commonly linked to ovarian cancer, but it can be present in other women, too. Knowing whether a woman has HRD is important, because it can influence the type of treatment she receives.
How HRD Can Affect Treatment
Up until recently, women with ovarian cancer were mostly given the same standard treatment, regardless of their unique biology. However, now that more is known about how ovarian cancer develops and grows, this is changing. Treatments can now be much more individualized. Doctors can take into account each woman's specific disease factors, including her cancer’s genetic makeup, when choosing a treatment plan.
Women with ovarian cancer who have HRD tend to respond better to certain treatments. According to researchers, these women respond better to platinum-based chemotherapy drugs like cisplatin (Platinol) and carboplatin (Paraplatin), as well as to a relatively new class of drugs known as PARP inhibitors.
PARP inhibitors are a targeted therapy that blocks the cancer cells' ability to fix their own genetic damage and render them unable to divide, thrive and multiply. Recent studies have shown that PARP inhibitors can extend the length of time a person is cancer-free, and help reduce the odds that a cancer will recur. In fact, the American Society of Clinical Oncology (ASCO) guidelines recommend PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.
The PARP inhibitor Zejula (niraparib) has been approved by the FDA for all women with newly-diagnosed ovarian cancer regardless of whether the tumor is HRD. The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer.
The PARP inhibitor Lynparza (olaparib) is approved for women newly diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2. Lynparza is also approved in combination with Avastin (bevacizumab) for women with HRD. Avastin is a blood vessel growth inhibitor, which works by starving the tumor of vital nutrients needed to grow.
Genetic testing, specifically testing for the BRCA gene and HRD, is highly recommended for women who have been diagnosed with ovarian cancer. Knowing about a mutation can help direct the course of treatment, for example what PARP inhibitor might be most effective to fight your cancer, but it can also help to protect your family. Because the BRCA gene is hereditary, if a BRCA mutation is found in your genetic makeup, the likelihood that other family members might eventually receive an ovarian cancer diagnoses is much higher. Frequent screening and sometimes prophylactic surgery can help them avoid cancer entirely, or up the odds of catching it early.
As with all cancer treatment, PARP inhibitors are not right for everyone, and it’s important to consult with your doctor about the risks and benefits of this treatment for you.
Dr. Engle is a gynecologic oncologist at Baptist Medical Group.
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