Personalized medicine uses information about an individual’s genetic make-up to deliver the right screening, prevention, or treatment options at the right time to achieve the best medical outcome. Genetic counseling, risk assessment, and genetic testing to determine inherited predisposition for diseases are important and growing areas of personalized medicine that further this goal.
Critics have raised concerns that identifying and treating people who are at risk for disease necessarily leads to “over-medicalization” of health care and increases cost and the possibility of causing harm. Evaluating the risks and costs versus benefits of disease prevention and control, however, is complex and depends on the disease in question, available screening and risk-management options, individuals or populations who are most at risk, and their level of risk for the disease. Given our limited resources and focus on containing health care costs, we will move beyond a one-size-fits-all approach to health only when we are willing to carefully consider each of these variables, rather than discounting all risk assessment, screening and prevention as over-treatment.
Not all risk is the same
Risk changes over the course of a lifetime, depending on genetics, lifestyle and other factors. Preventive care and screening recommendations for people of average risk are based on studies of thousands of people in the general population—sometimes they are not adequate for people who have a higher risk for a particular disease. Personalized medicine allows us to identify people with higher-than-average risk and provide interventions that can improve their health outcomes. For example, the American Cancer Society recommends annual mammograms beginning at age 40 for women with an average risk for breast cancer. But women with BRCA mutations, who face a higher lifetime risk for breast cancer at a younger age, and tumors that may develop faster and more aggressively, need more frequent and rigorous screening that begins at an earlier age and involves annual MRI surveillance.
Not all diseases are the same
Diseases develop and behave differently and have different impact, morbidity, and mortality, which must be considered when weighing the cost and risks compared to the value of screening and prevention. Impact of a disease includes the number of people affected and the consequences of diagnosis and treatment on survival and quality of life. Basal cell skin cancer and ovarian cancer illustrate these differences.
Roughly 2.8 million people in the United States are diagnosed with basal cell skin cancer yearly, compared to about 22,000 ovarian cancer diagnoses. Basal cell cancers can be detected through skin exams, and almost all cases are cured. With no reliable detection or screening, ovarian cancer is most often found late, when the five-year cure rate is less than 50%. Ovarian cancer patients require extensive surgery, chemotherapy, and sometimes radiation, often with profound negative effects on quality-of-life. Although more people are affected by basal cell cancer, more people die of ovarian cancer. Screening and prevention recommendations for a common, detectable, and treatable disease like basal cell cancer require different considerations than those for a less common cancer (like ovarian cancer) that cannot be detected early, carries a poor prognosis, and is accompanied by aggressive treatment. It makes sense to focus efforts and apply technology to identify those in the highest risk category for deadly diseases such as ovarian cancer and prevent them whenever possible.
Not all interventions have the same risks or benefits for everyone
We can predict risk for some diseases like Huntington's, for which we have no effective or proven intervention. However, many diseases, such as breast cancer, have interventions that lower the risk for or improve the odds of detecting the disease at it’s earliest and most treatable stage. Each disease intervention option has unique risks, costs, and benefits that should be considered individually.
MRI is a sensitive tool that can detect breast cancers that are too small for a mammogram to find. But MRI screenings are expensive, and they often find suspicious but harmless breast changes, requiring a biopsy to assure that they are benign. For these reasons, experts don’t recommend screening breast MRI for women of average risk for breast cancer. Women at high risk have a greater likelihood of an abnormality being actual cancer, and that often tips the scales in favor of increased surveillance, even if that means a greater chance of needing a biopsy. Long-term research on high-risk women shows that MRI detects breast cancers at an earlier stage resulting in less extensive treatment.
Having a BRCA mutation raises the lifetime risk for ovarian cancer up to 50%, compared to 1.5% for women with average risk. Prophylactic bilateral salpingo-oophorectomy (removal of the ovaries and tubes) is the most effective way to reduce ovarian cancer risk, but like all surgery, the procedure has its own potential for risk and harms: complications from anesthesia, infection, and early menopause, which can be associated with long-term health and quality-of-life consequences. Surgery is also costly. On the other hand, research has shown that BSO improves survival in high-risk women. Given the costs, risks, and benefits of prophylactic surgery versus the consequences of an ovarian cancer diagnosis, this intervention offers more value to women at very high risk and less value to average risk women.
Research shows that prostate cancer screening using PSA increases detection of this cancer but may not improve survival for many men. PSA screening has risks and limitations including: many of the cancers found are not symptomatic and will not affect life-span or quality-of-life; PSA tests can yield many false-positive results leading to unnecessary biopsies; treatment of prostate cancer can lead to side effects in many patients. Given this, the United States Preventive Services Task Force (USPSTF) issued guidelines that recommended against PSA screening for men of average risk. However, recent research suggests that men with BRCA 2 mutations face a higher lifetime risk for more aggressive, younger-onset, prostate cancer than men in the general population. Applying personalized medicine to their guidelines, the USPSTF qualified that "This recommendation...does not consider PSA-based testing in men with known BRCA gene mutations who may be at increased risk for prostate cancer."
Not all information is clinically useful
Before BRCA mutations were identified, individuals with a strong family history of cancer had no way to know whether they had inherited a very high risk for cancer. Basing their risk on family history alone, these women sometimes pursued prophylactic surgery, even though their lifetime risk was no higher than the average woman’s. The availability of BRCA testing improves decision-making for high-risk women, giving them the opportunity to learn more about their personal risk and make evidence-based health care decisions.
The same advances that make BRCA genetic testing possible have also led to the development of other tests that may not be as useful. Genetic testing allows researchers to understand how diseases develop and design better options for screening, prevention and treatment. But not all genetic tests should be offered to the general public for decision-making purposes; particularly those that do not provide “actionable” information that people can use to improve their health or quality of life.
Informed decision-making
Given credible information, people are capable of weighing the costs, harms, and benefits of different medical interventions. Genetics experts can help to guide people through the maze of factors described in this blog to make personal informed decisions about their care.
BRCA is just the tip-of-the-personalized medicine iceberg. Genetic tests have been developed that can look at tumor cells to determine the best treatment or predict the likelihood of people having side-effects from a particular therapy. Granted, personalized medicine is not an exact science, and we are not yet able to apply it to all people and all diseases. But it makes sense to use evidence-based interventions to save and improve the quality of as many lives as we can. As a society, we need to continue to invest in the research, translation, and application of personalized medicine, risk assessment, and genetic testing to determine the best candidates for the best interventions at the best time.