Douglas A. Levine, MD
As time goes on, there will be an interaction between molecular pathology and clinical pathology where genetic testing can lead to a more accurate pathologic diagnosis, according to Douglas A. Levine, MD.
The early identification of BRCA
mutations can significantly help inform future treatment choices for patients with ovarian cancer. There is no routine testing for BRCA
mutations in endometrial cancer but physicians can screen for Lynch syndrome, which can be related to germline mutations.
“All ovarian cancers, endometrial cancers, lung cancers, and other types of cancers are each specific subtypes of cancer that have a specific genetic makeup, receive specific treatments, and now have different prognoses,” explains Levine.
In an interview with OncLive
, Levine, a professor in the Department of Obstetrics and Gynecology, Director, Division of Gynecologic Oncology, NYU Langone Medical Center, discusses the role of pathology in endometrial and ovarian cancer, and highlights when a patient should be tested for BRCA
Onclive: Can you give an overview of your presentation from the Congress of Oncology Pathology meeting?
: We're talking about the interaction between oncologists and pathologists. Additionally, I talked about homologous recombination DNA repair defects in ovarian cancer, how that leads to PARP inhibition therapy, and the various recently approved FDA indications for PARP treatment. I also talk about microsatellite instability in endometrial cancer and how that has led to recent FDA approval of checkpoint blockade immune-oncology treatments.
Can you discuss how pathology, tissue sampling, and repeat biopsies factor into ovarian and endometrial cancers?
Pathologists and oncologists work closely together to treat cancer patients. In ovarian and endometrial cancer, the tumor can evolve over time, mostly due to prior treatments. This is particularly the case with ovarian cancer based on what chemotherapy agents have been given. One of the important factors regarding tumor evolution is if the tumor has BRCA germline or somatic mutations since secondary mutations can develop over the course of treatment. Those secondary mutations can make a treatment-sensitive tumor become treatment-resistant.
Additionally, factors that can develop over time would include selection for other mutations that could be directly targeted, or the disappearance of mutations that could have led to prior sensitivity.
Is the role of pathology in endometrial and ovarian cancer different from other cancers?
The role of pathology is very important for all cancer treatment. Cancer treatment starts with having the correct diagnosis and as we know, all cancers are not one disease. All ovarian cancers, endometrial cancers, lung cancers, and other types of cancers are each specific subtypes of cancer that have a specific genetic makeup, receive specific treatments, and now have different prognoses.
It's important to get the right pathologic diagnosis. On the other hand, it is very difficult for pathologists to diagnosis high-grade tumors. As time goes on, we'll see an interaction between molecular pathology and clinical pathology where the genetic testing and the genomic information can lead to more accurate pathologic diagnosis. In some cases, it's indicated as being very important whereas in others it's a waste of money.
How can you determine which cases are important and which would be a waste of money
That is where individual studies, academic studies, and national studies, can show the benefits and determine where this is important. We know for BRCA-associated ovarian cancer, genetics is very important. Pathology can lead you to suspect that a patient has a BRCA
-mutated tumor but you can't diagnose it without genetics, and that is going to affect treatment.
On the other hand, microsatellite instability testing can be done at a pathology laboratory with the immunohistochemistry. In some cases, you need to augment that with germline genetics. Depending on the situation, with some difficult to diagnosis tumors, such as high-grade endometrial cancers, it can be hard to determine whether it is endometrioid or serous. A panel of protein markers can help to distinguish this and we've known that for a long time. You don't always need genetics to make that diagnosis.
At what stage should patients with ovarian and endometrial cancer be tested for BRCA1/2 mutations?
Every newly-diagnosed patient with ovarian cancer should undergo genetic testing for BRCA1/2