Banu Arun, MD, discusses how the role of genetic testing is evolving in breast cancer with the development of new targeted agents.
Banu K. Arun, MD
As targeted therapies for actionable mutations move through the pipeline, the importance of genetic testing continues to increase in breast cancer, according to Banu Arun, MD.
In recent years, the FDA has approved 2 PARP inhibitors—olaparib (Lynparza) and talazoparib (Talzenna)—for patients with HER2-negative metastatic breast cancer harboring a germline BRCA mutation. Other hereditary genes that could potentially have a role in making treatment considerations going forward include PALB, ATM, and CHEK2 mutations.
In an interview with OncLive, Arun, co-medical director of breast medical oncology in The Clinical Cancer Genetics Program at The University of Texas MD Anderson Cancer Center, discussed how the role of genetic testing is evolving in breast cancer with the development of new targeted agents.
OncLive: What is the current role of genetic testing in breast cancer?
Arun: Germline testing for hereditary breast cancer has made its practice into 1 of the important tests for breast cancer treatment. There are already guidelines for hereditary genetic testing for BRCA1 and BRCA2. Most of us follow the NCCN guidelines; that criteria includes testing all patients before age 45 or all patients with triple-negative breast cancer before the age of 60. Outside those age ranges, there is also criteria for patients with family history of breast cancer, ovarian cancer, any individual with pancreas cancer or any individual with metastatic prostate cancer is eligible.
What are the implications of genetic testing?
There are multiple implications for genetic testing in breast cancer. First, for the patient with breast cancer, it can help to determine, for example, if there is a BRCA mutation, or the risk of contralateral breast cancer. At the time of deciding for surgery, the patient could opt for double mastectomy to prevent contralateral breast cancer. This approach should be discussed though in detail with the patient and her surgeon.
It also has therapeutic implications. Now that PARP inhibitors are FDA approved for metastatic breast cancer with germline BRCA mutations, physicians could use PARP inhibitors for their patients with metastatic BRCA-positive breast cancer. The response rate is about 60% for these agents. We also know the platinums induce an up to 60% response rate in patients who are BRCA mutation carriers for metastatic breast cancer. Therefore, platinums could be considered for treatment as well.
The other implications for patients besides treatment is also for screening. We know that ovarian cancer risk is up to 45% in BRCA1 and up to 25% in BRCA2 carriers. Doing preventable oophorectomy is recommended per the guidelines for patients in their late thirties or early forties.
There are also family implications. Once you find a mutation in the patient, each first-degree relative, has a 50% risk of carrying the mutation; ideally these family members should consider genetic testing (what we call predicative testing). If they are positive, then they would do risk management interventions, such as adding MRI to their breast screening, considering double mastectomy, ovarian screening, or oophorectomy. If it’s a BRCA2 mutation carrier, they should do pancreas screening, screening for melanoma, prostate screening, amongst others.
There are also other genes that are related to hereditary breast cancers such as PALB2 mutations, ATM, and CHEK2. Those tests can be ordered all together with BRCA1 and BRCA2 on panels. If patients are positive, it might not have immediate therapeutic implications at this time as we do not have sufficient data. For example, we don’t have enough data to recommend bilateral mastectomy, however, for unaffected family members, it can have screening implications, such as adding MRIs to the screening or screening for other cancers.
Could you highlight the importance of detecting a BRCA mutation in these patients?
Patients with BRCA1- and BRCA2-mutated metastatic breast cancer are eligible to be treated with PARP inhibitor therapies and targeted agents based on 2 prospective randomized trials comparing PARP inhibitors to standard-of-care chemotherapy. The response rate was almost doubled with PARP inhibitors, and the duration of response was statistically significantly prolonged by about 3 months in both of the studies. The FDA approved these agents for the treatment of patients with metastatic breast cancer with BRCA mutations. Also, platinums can be used in these patients as well. PARP inhibitors and platinums induce a up to 60% response rate.
What tests do you use for genetic testing in breast cancer?
There are several CLIA-certified companies that offer germline testing in the blood. These are commercially available tests covered by the patient’s insurance if they fit the criteria.
How frequently is genetic testing being used in breast cancer clinical trials?
There are multiple clinical trials looking at PARP inhibitors in combinations. This requires that the patients undergo germline genetic testing for BRCA mutations. Some of the trials also include other hereditary mutations, such as PALB2. Again, if patients are found to have those mutations, they may be eligible for clinical trials.
We, for example, are about to open a study with using PARP inhibitors plus other targeted agents for patients with metastatic breast cancer with BRCA mutations. The availability of these treatments as well as clinical trials will increase BRCA testing for patients with breast cancer.
What advice would you like to share with community oncologists in regard to genetic testing for patients with breast cancer?
My message would be to see whether the patient fits criteria for genetic testing for BRCA1 and BRCA2, usually using the NCCN guidelines and updates. For the other genes, I think they have to pay attention to family history. If they have a patient with, for example, breast and uterine cancer, and a family history of thyroid cancer, maybe the patient is a candidate for PTEN mutation testing. Some patients with breast cancer have family members with colon cancer and ovarian cancer, therefore checking for Lynch syndrome mutations might be helpful. Taking into account personal history of cancer, age of onset is important, as well as considering any family history of different types of cancer.