The Sequence 9/26-10/2
We May Need to Re-think Who Receives Genetic Testing for Breast Cancer, Frozen Embryo Transfers Linked with High Blood Pressure Risks in Pregnancy, Barriers to Receiving Exome Sequencing Testing
We may need to re-think who receives genetic testing for breast cancer
Healthcare professionals caring for patients with breast cancer can choose to follow any of various existing guidelines to inform them which patients to order genetic testing on. Insurance companies also use these guidelines to determine which genetic tests should be covered.
Guidelines published by the National Comprehensive Cancer Network, or NCCN, state that patients at high-risk for an inherited form of cancer should receive genetic testing. Some examples of what make a patient ‘high risk’ include a family history of breast cancer; those who are 45 or younger when they're diagnosed; and those with Ashkenazi Jewish ancestry. Guidelines published by The American Society of Breast Surgeons, however, recommend a different approach: Offer genetic testing to all patients who have a personal history of breast cancer.
So which guidelines should we follow?
That’s where this article by Michelle Andrews comes in. Andrews points out that it may make sense to only order genetic tests that will have clear impact on clinical care.
Don’t all genetic testing results have impact on clinical care?
No. Sure, there are some genetic variants that offer clear impact on treatment. Knowing whether breast cancer is inherited may help in facilitating the decision of which type of surgery to pursue, may help guide treatment decisions (for example patients who have BRCA1 or BRCA2 mutations may be good candidates for a certain type of drug called a PARP inhibitors), and inform who in the family may be at an elevated risk of developing breast cancer. However, many genetic tests will result in what we call variants of uncertain significance, or variants that may or may not be harmful. When these results are on the report, there is no immediate action that can be taken, and it is recommended the patient follow up on those variants in the future to see whether they are considered harmful in the future. Another uninformative result is a variant in a gene that we know can increase risk for breast cancer, but which has no clear guidance on what to do next. It may cause more stress for someone to decide whether to pursue a double mastectomy after knowing they have an increased risk for breast cancer (and/or breast cancer recurrence), but without any existing guidelines on whether a double mastectomy is recommended or not. Finally, and an extension of that last point, there aren’t enough genetic counselors and other genetic experts around to facilitate decision making for all of these patients.
The takeaway?
This is another article that comes down to the question: Just because we can, should we? If we begin doing genetic testing on all patients with a personal history of breast cancer, as opposed to those at high risk if an inherited cancer, we need to be sure there are clear guidelines out there for people to follow based on their results, and enough providers that can interpret them.
Frozen Embryo Transfers Linked with High Blood Pressure Risks in Pregnancy
Researchers examined the data from medical birth registries of nearly 2.4 million women to understand rates of high blood pressure in women who underwent IVF versus women who did not. They further broke down the data to understand the difference between hypertension rates in women who underwent IVF with frozen embryos vs. women who underwent IVF with fresh embryos.
Give me the rundown on in vitro fertilization (IVF)
In vitro fertilization (IVF) is the fertilization of an egg and a sperm to create an embryo outside the body, in a laboratory dish. Once the fertilized egg divides and becomes en embryo, the embryo can either be immediately placed into the woman’s womb for pregnancy, or it can be frozen for future use.
How is this relevant to genetics?
PGT! Preimplantation genetic testing (PGT) is the process of testing embryos after IVF prior to fertilization in the womb in order to test for genetic mutations. This is usually done when couples are at high-risk of having a child with a genetic condition based on their genetic carrier status. This can include testing the embryo for a single, specific gene mutation that mom or dad carries, or for an entire extra or missing chromosome (aka aneuploidy). By doing this, only the embryos without a genetic mutation or variation are transferred for fertilization. (See this post on the use of PGT in women with few embryos available).
How high was the risk for hypertension in the women who underwent IVF?
The team concluded that IVF using frozen embryos may be associated with a 74% higher risk of hypertensive disorders in pregnancy than those who used fresh embryos. This was after controlling for things like age of mother and other risk factors.
The risk for hypertension in women that used fresh embryos was similar to that of natural conception.
What's the takeaway?
Moving forward, it will be important to include the potential elevated risk of hypertension when using frozen embryos for IVF in conversations about reproductive choices.
Barriers to receiving exome sequencing testing
Although exome sequencing (ES) genetic testing has become a frequently ordered test in the pediatric setting, it is often a long process from the time the test is recommended by the ordering provider to the time the testing begins.
Researchers at Stanford Medicine studied pediatric patients who received ES genetic testing in order to understand the barriers faced. They looked at things like the amount of time between the provider requesting a prior authorization for testing from insurance and sample collection, the amount of time for insurance to make a decision about whether they would cover the test, and the amount of time it takes some individuals to schedule with a genetics provider qualified to order testing. They describe what factors correlate with a longer time between the test being ordered and the test beginning.
What is exome sequencing?
Exome sequencing is a test that tries to identify harmful changes in the DNA by sequencing the ~30,000 genes in the ‘exome’, or the portion of our DNA that codes for protein and has function.
So why does the process take so long?
One of the major barriers is insurance approval. Many times, insurance will consider ES unnecessary, questioning the judgment of providers ordering it and whether the patient will actually benefit from testing. The process of submitting a letter of medical necessity to insurance companies to prove benefit and then waiting for a preauthorization is one of the first reasons testing is delayed.
Another reason testing can be delayed is limited access to services. A limited and understaffed genetics workforce can be common in less densely populated areas. Nationally, genetics clinics have increasingly higher patient caseloads and longer appointment wait times than other subspecialties.
What exactly did the group find?
Of 115 cases analyzed, the average time from provider preauthorization request to sample collection took 104.4 days, and income was negatively correlated with the length of the insurance decision interval.
Another time-consuming step was scheduling a second appointment with the providers to obtain consent and draw the patient’s sample after insurance authorization, with the average amount of time being 48.1 days.
Are there ways to speed this up?
Prior authorization decisions by insurance companies can be made more quickly if adequate information and clinical reasoning for ordering testing is provided up front. This would decrease the need for excess communication with insurance companies. On the flip side, insurance companies could consider identifying areas of improvement and eliminating various obstacles to minimize the number of days it takes to approve a test.
The wait time between insurance approval and a second patient appointment could decrease first by more promptly communicating insurance authorization to the clinical team so that the clinic can begin scheduling the appointment. Then there’s the wait-time for the second genetics appointment. The date of the patient’s next appointment is dependent on several factors, such as the family’s availability, accessibility of the clinic, and the availability of the health care provider. If genetics clinics and staff become more widely available, that wait time will decrease.
What’s the takeaway?
The wait for prior authorization is only part of the delay. The rest, including the wait to schedule and undergo consent for testing and sample collection, comes down to accessibility of genetics providers and clinics.