Emma Perez, Genetic Counselor
A valid question that is often asked when discussing PRS implementation is “how will this information be used in clinical care in the absence of clinical guidelines for PRS”? One approach is to ensure PRS risk information is presented in a way that mirrors the risk numbers that current guidelines recommend. For example, 10 year-risk for an ASCVD event is currently a standard way of communicating risk of plaque-related cardiovascular disease, and guidelines recommend specific pathways for women based on their lifetime risk of breast cancer. Another way in which this information can be used is in shared decision making.
Shared decision making occurs when there is a decision to be made regarding a patient’s medical care but there isn’t a clear right or a wrong path. Because of this uncertainty, the limitations and benefits of different options are presented to the patient by the provider. Together they can make a decision that is in the patient’s best interest.
A high PRS indicates that you are at increased genetic risk of disease, but in the absence of clear guidelines of what to do to mitigate this risk, shared decision making can be used by providers to help guide the path forward. In prostate cancer, for example, the USPSTF(United States Preventive Services Task Force) recommends shared decision making between patient and physician to explore whether a Prostate Specific Antigen (PSA) test should be pursued. In addition to known risk factors such as race and family history, PRS can be another piece of information to incorporate into the decision making conversation.
Another example is a woman with a known PALB2 pathogenic mutation. Here, PRS information can be used to provide additional information to guide the patient with potential surgery and screening decisions. The NCCN (National Comprehensive Cancer Network) says that a risk-reducing mastectomy for carriers of a PALB2 P/LP variant may be considered. For someone with a PRS in the lower range, they may opt to continue their enhanced screening rather than pursue a double mastectomy, or maybe someone would feel more comfortable waiting a few years before deciding to have a mastectomy.
Lastly, if we consider coronary artery disease (CAD) risk assessment, the 10-year ASCVD risk score can put a patient in the “intermediate risk” range. If someone is in the intermediate range and has a risk enhancing factor such as a high PRS (O’Sullivan et al., 2022), a discussion with the patient is recommended around initiating a moderate intensity statin. During this discussion, the ASCVD score and the PRS together can guide the discussion.
In the three scenarios outlined above, of course family history plays a role in shared decision making, but PRS can be one more variable to base the shared decision making conversation.
Very recently, the use of PRS in shared decision making in the cancer setting has been discussed by Gallagher et al. in the context of PRS. I would certainly recommend giving it a read and Fig 1. beautifully depicts this shared decision making framework.