Ovarian cancer, a type of cancer that originates in the fallopian tubes and ovaries, poses a significant challenge in the realm of women's health due to its often asymptomatic nature and late-stage diagnosis. However, advancements in multidisciplinary care that include genetic testing have provided valuable tools in identifying individuals at increased risk, thereby improving early detection and preventive measures, as well as new treatment options.
As part of today’s personalized medicine approach to treating cancer, there is an important role for genetic testing in understanding and managing ovarian cancer risk, diagnosis and treatment.
Risk of ovarian cancer
Ovarian cancer is notoriously difficult to detect early. Symptoms, when they do appear, are often vague and can be mistaken for less serious conditions. Late diagnosis results in a high mortality rate, as the cancer is most frequently discovered at an advanced stage. The realization that genetic factors contribute significantly to ovarian cancer has revolutionized the multidisciplinary approach to understanding and managing the disease.
Genetic predisposition plays a crucial role in ovarian cancer risk. BRCA1 and BRCA2 are the most well-known genes associated with hereditary breast and ovarian cancer syndrome (HBOC). Mutations in these genes significantly increase the likelihood of developing ovarian cancer, with BRCA1 mutations conferring a lifetime risk of approximately 39% and BRCA2 mutations a risk of about 11%-17%. These risks are increased over the general population’s 1%-2% risk of developing ovarian cancer. Genetic testing for BRCA1 and BRCA2 mutations has become a critical tool in identifying individuals at high risk.
The benefits of genetic testing are many. For individuals with a family history of ovarian or breast cancer, testing can provide clarity about risk levels. Those identified as carrying BRCA mutations can take preventive measures, such as increased surveillance, prophylactic surgeries or chemoprevention (taking medications that reduce hormonal interactions to reduce risk). For instance, women with BRCA mutations may opt for prophylactic salpingo-oophorectomy (removal of the ovaries and/or fallopian tubes) to significantly reduce their risk of ovarian cancer. Furthermore, genetic testing informs family members of their potential risk, offering them the opportunity for early testing and preventive strategies.
However, genetic testing is not without its limitations. Not all cases of ovarian cancer are linked to BRCA mutations, as there are other genetic mutations associated with the disease, such as those in the Lynch syndrome-related genes (MLH1, MSH2, MSH6, PMS2, EPCAM). Moreover, genetic testing does not guarantee that cancer will be prevented; it merely provides information about increased risk. The decision to undergo genetic testing and subsequent preventive measures involves complex considerations, including emotional, ethical and financial factors. Northside Hospital Cancer Institute has a team of genetic counselors available to support patients and families with these decisions around testing and results.
Moreover, there is an ongoing need to address barriers and disparities in access to genetic testing and subsequent care. Socioeconomic factors, insurance coverage and geographic location can all impact an individual’s ability to access and afford genetic testing. Again, the team of genetic counselors at Northside can guide patients who need testing to make informed decisions about their healthcare.
Genetic testing expands treatment options
Recent advancements in targeted therapy have introduced PARP inhibitors as a promising treatment option for ovarian cancer. PARP (poly (ADP-ribose) polymerase) inhibitors, such as olaparib, rucaparib and niraparib, have revolutionized the management of ovarian cancer, particularly for patients with BRCA1 or BRCA2 mutations and other conditions.
The mechanism of action for PARP inhibitors involves the targeted inhibition of the PARP enzyme, which is crucial for repairing single-strand DNA breaks. In cancer cells with defective BRCA genes, the repair of double-strand breaks is already impaired. By inhibiting PARP, these drugs work against the cancer cells’ inability to repair DNA damage and ultimately prevent abnormal cell growth or slow it down.
Clinical trials have demonstrated that PARP inhibitors can significantly improve progression-free survival in patients with ovarian cancer. For instance, studies have shown that olaparib can delay disease progression by several months in patients with BRCA mutations. However, challenges remain, including the development of resistance to PARP inhibitors and managing side effects. Ongoing research aims to optimize treatment regimens and explore combination therapies to enhance efficacy and overcome resistance. Overall, PARP inhibitors represent a significant advancement in the treatment landscape of ovarian cancer, offering hope for improved outcomes and quality of life for many patients.
Why genetic testing — and how?
In conclusion, genetic testing has significantly advanced our understanding of ovarian cancer risk, providing insights that enable targeted preventive strategies and early intervention. While it presents clear benefits, including personalized risk assessment and preventive options, there are inherent limitations and challenges. Continued research, improved access to genetic testing and comprehensive support for individuals at risk are essential to harness the potential of genetic advancements in the fight against ovarian cancer.
As we move forward, the integration of genetic information into cancer care promises a future where personalized medicine offers enhanced protection and better outcomes for those at risk and who face the disease.
Genetic testing is recommended for individuals who have a personal or family history of ovarian cancer. Ask your doctor for a referral to a cancer genetics program to speak with a genetic counselor about the benefits and limitations of genetic testing for determining treatment options, risk reduction and recommended surveillance.
Learn more about cancer genetics at Northside Hospital Cancer Institute.
