The “Previvors” of Hereditary Cancer: How Genetic Screening for Hereditary Cancer Risk Has Transformed Cancer Care

Written by: Allison Hess

Edited by: Helen Zheng, Felix Yuan, and Ashika Gullapalli

Ilustrated by: Kayla Kupietzky

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Introduction 

Since the first genetic tests for mutations in the BRCA1/2 gene, associated with increased risk of breast and ovarian cancer, became clinically available in 1996, the use of genetic screening for hereditary cancer risk has become increasingly more common [1]. With the availability of such tests, a previously undefined patient population emerged in oncology whose lifetime risk of certain cancers was high due to hereditary risk factors but who had not been diagnosed with cancer themselves. This population, later dubbed “previvors” by the group Facing Our Risk of Cancer Empowered (FORCE), facing a unique set of clinical and social-emotional challenges, has shaped the field of oncology, preventative cancer care, and cancer research over the past two decades [2]. Previously only referred to using the medical term “unaffected carriers,” indicating that a patient carries a cancer-associated mutation but has not been affected by a personal diagnosis of cancer, many patients who adopted the term “previvor” (meaning survivor of cancer predisposition) feel it acknowledges the many ways these patients are affected by their diagnosis, even if they have not developed cancer [3]. As awareness of hereditary cancer syndromes increases and genetic testing becomes more accessible to many patients, the number of previvors continues to rise. This article will explore the science behind hereditary cancer risk and genetic screening, the unique clinical, social, and informational needs of “previvors,” and the impact of genetic screening and preventative medicine on the field of oncology.

The Science Behind Hereditary Cancer Risk

The complexity of clinical care and the diversity of experiences of previvors are largely driven by the science behind hereditary cancer risk. Over 500 documented genes have been determined to have cancer-related activity, with many more identified as having strong indications for a role in cancer [4]. Broadly speaking, the most common mutations associated with cancer risk occur in genes that fall into three categories: oncogenes, tumor suppressor genes, and DNA repair genes [5]. One helpful way to think about the role of these mutated genes in cancer development is to think about cell growth and division, like driving a car. In order to function, a car needs to be able to move, but it also critically needs to be able to stop—the same is true for the replication of our cells. 

Proto-oncogenes are genes that are not always active but, when “turned on,” stimulate the growth and division of our cells, which is analogous to pressing down on the gas pedal in a car. However, mutations in these genes can cause them to be converted to oncogenes, which can be thought of like a gas pedal that is stuck down, causing the car to move forward at dangerous speeds [6]. Tumor suppressor genes are the functional opposites of proto-oncogenes and oncogenes, encoding proteins that restrict cell growth and division and can even cause programmed cell death, or apoptosis [6]. These genes can be thought of as genetic “brakes” on cell growth and division, and mutations in these genes can also prevent the ability of a cell to slow down or stop these processes. Another set of genes, DNA repair genes, act as the mechanics responsible for repairing the car, correcting mistakes made during DNA replication, and preventing mutations from being passed down to the product cells [6]. When DNA repair genes are nonfunctional, other mutations that further impact cell growth and division can accumulate [6]. 

Because all cancer is caused by these mutated genes, all cancer is genetic [7]. However, only between 5 to 10 percent of cancer cases are hereditary, meaning the genetic mutations are passed down from parents to children [8]. Most mutations causing cancer are acquired spontaneously by individual cells either during errors in normal cell division processes or in response to environmental hazards that can cause DNA mutations, such as UV light or chemicals, rather than being passed down hereditarily [8]. In any of these cases, a single mutation does not cause cancer on its own, just like how a car with weak brakes can still eventually be brought to a stop by releasing the gas. A combination of several of these cellular control measures must fail for cancer to develop, which is why some people with hereditary cancer mutations do not develop cancer in their lifetimes. These hereditary mutations leave patients more vulnerable to subsequent mutation “hits,” as it will require fewer environmentally-triggered or random mutations to overcome cell cycle control measures, but these subsequent mutations also may never arise.

Benefits of Genetic Cancer Screening

This idea that cancer risk is determined by a combination of genetic factors and subsequent genetic “hits” that can be caused by environmental and behavioral risk factors that can potentially be mitigated means that identifying a patient’s genetic predisposition to cancer can be important for making informed decisions about their health. The NIH recommends testing for patients diagnosed with cancers associated with more prevalent mutations before the age of 50, as well as those with personal or family histories that suggest the possibility of a hereditary cancer syndrome [9]. In patients who have already been diagnosed with cancer, determining whether they have a hereditary cancer syndrome is important for making informed decisions about pursuing treatment options that may further increase their risk of developing other cancers [9]. For patients who have not been diagnosed with cancer but whose family or medical histories implicate hereditary cancer syndromes, correctly identifying a patient’s elevated risk of developing certain cancers before they emerge can be instrumental in promoting better long-term health outcomes through routine screening that can diagnose cancer earlier and engaging in preventative behavioral or medical measures to reduce their risk of developing certain cancers [10-11]. 

Previvors: Unique Challenges Faced and Clinical Management

Despite the advantages offered in preventing and treating cancer, when patients are made aware of their genetic cancer risk, previvors can also face unique challenges associated with their diagnosis. Although studies conducted on patient distress after a positive cancer-associated genetic test show that increases in anxiety and distress associated with diagnoses are usually transient in previvors, these studies were conducted with patients who received robust genetic counseling about the specific genes they were being tested for before their testing to make an informed decision about whether or not they wanted to know their cancer risk status [12, 13, 14]. Today, as larger genetic testing panels, including a wider pool of genes, become more available, it is increasingly difficult to counsel patients about the prognoses and treatment options for every mutation included, limiting their ability to anticipate the psychological risks associated with a positive test result and provide informed consent [14].

Additionally, although access to healthcare interventions such as increased cancer screening regimens and preventative therapies mitigating improving prognoses for these patients is commonly cited as the main benefit of genetic cancer screening, the reality of accessing this care is complicated for many previvors. Although the Affordable Care Act (ACA) requires insurers to cover several cancer screenings at no cost to patients, the type and frequency of cancer screenings recommended for many previvors far exceed the scope of those provided under the ACA [15]. This can force previvors to pay thousands of dollars a year out-of-pocket for cancer screening such as MRIs, engage in long appeals processes with their health insurers, which delay their care, or forgo some recommended screenings entirely [15]. Beyond access to recommended screening, previvors often face several significant health and family planning decisions after their diagnosis, such as whether to pursue risk-reducing surgeries (such as mastectomies for those with high risk of breast cancer) or in vitro fertilization (IVF) and preimplantation genetic testing if they plan to have biological children to prevent passing on cancer-associated genetic mutations to their children [16]. Though these choices grant previvors agency over their care, they can also be daunting in what is a complex information ecosystem surrounding cancer risk, preventative surgeries, and fertility care [17]. 

Current Utilization of Genetic Testing for Hereditary Cancer Risk

Genetic testing for hereditary gene mutations associated with increased cancer risk can be instrumental in informing the clinical care of patients who have already developed cancer. It may also improve prognoses and provide agency to previvors in making healthcare decisions. However, despite the potential benefits of genetic screening for hereditary cancer risk in improving patient outcomes and empowering previvors to make informed decisions about their health, many at-risk patients never access this testing, and improvements to support for previvors after testing in accessing follow-up care, social support, and in making decisions surrounding their diagnosis is critical to the wellbeing of this patient population [18]. 

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References

[1] Petrova, D., Cruz, M., & Sánchez, M.-J. (2022). BRCA1/2 testing for genetic susceptibility to cancer after 25 years: A scoping review and a primer on ethical implications. The Breast, 61, 66-76. https://doi.org/10.1016/j.breast.2021.12.005

[2] Facing Our Risk of Cancer Empowered. (n.d.). Our mission and impact. Facing Our Risk of Cancer Empowered. https://www.facingourrisk.org/about-us/mission-and-impact

[3] Mueller, B. (2020, September 30). What’s in a name: Previvorship & patient advocacy. Basser Center for BRCA. https://www.basser.org/resources/whats-name-previvorship-patient-advocacy

[4] Sondka, Z., Bamford, S., Cole, C. G., et al. (2018). The COSMIC Cancer Gene Census: Describing genetic dysfunction across all human cancers. Nature Reviews Cancer, 18(11), 696–705. https://doi.org/10.1038/s41568-018-0060-1

[5] Chung, D. C., & Rustgi, A. K. (1995). DNA mismatch repair and cancer. Gastroenterology, 109(5), 1685–1699. https://doi.org/10.1016/0016-5085(95)90660-6

[6] Chow, A. Y. (2010). Cell cycle control by oncogenes and tumor suppressors: Driving the transformation of normal cells into cancerous cells. Nature Education, 3(9), 7.

[7] Nowak, M. A., & Waclaw, B. (2017). Genes, environment, and “bad luck”: Explaining cancer risk in a statistical sense. Science, 355(6331), 1266–1267. https://doi.org/10.1126/science.aam9746

[8] Hart, S. N., Polley, E. C., Yussuf, A., Yadav, S., Goldgar, D. E., Hu, C., LaDuca, H., Smith, L. P., Fujimoto, J., Li, S., Couch, F. J., & Dolinsky, J. S. (2020). Mutation prevalence tables for hereditary cancer derived from multigene panel testing. Human mutation, 41(8), e1–e6. https://doi.org/10.1002/humu.24053

[9] National Cancer Institute. (n.d.). Genetic testing for inherited cancer risk. U.S. Department of Health and Human Services. Retrieved January 14, 2025, from https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing

[10] Singh, D. N., Daripelli, S., Elamin Bushara, M. O., Polevoy, G. G., & Prasanna, M. (2023). Genetic Testing for Successful Cancer Treatment. Cureus, 15(12), e49889. https://doi.org/10.7759/cureus.49889

[11] Lima, S. M., Nazareth, M., Schmitt, K. M., Reyes, A., Fleck, E., Schwartz, G. K., Terry, M. B., & Hillyer, G. C. (2022). Interest in genetic testing and risk-reducing behavioral changes: results from a community health assessment in New York City. Journal of community genetics, 13(6), 605–617. https://doi.org/10.1007/s12687-022-00610-2

[12] Hamilton, J. G., Lobel, M., & Moyer, A. (2009). Emotional distress following genetic testing for hereditary breast and ovarian cancer: a meta-analytic review. Health psychology : official journal of the Division of Health Psychology, American Psychological Association, 28(4), 510–518. https://doi.org/10.1037/a0014778

[13] Halbert, C. H., Stopfer, J. E., McDonald, J., Weathers, B., Collier, A., Troxel, A. B., & Domchek, S. (2011). Long-term reactions to genetic testing for BRCA1 and BRCA2 mutations: does time heal women's concerns?. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 29(32), 4302–4306. https://doi.org/10.1200/JCO.2010.33.1561

[14] Halbert, C. H., Stopfer, J. E., McDonald, J., Weathers, B., Collier, A., Troxel, A. B., & Domchek, S. (2011). Long-term reactions to genetic testing for BRCA1 and BRCA2 mutations: does time heal women's concerns?. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 29(32), 4302–4306. https://doi.org/10.1200/JCO.2010.33.1561

[15] Facing Our Risk of Cancer Empowered. (n.d.). High-risk individuals often struggle to get insurance coverage of health services. Facing Our Risk of Cancer Empowered. https://www.facingourrisk.org/privacy-policy-legal/advocacy/high-risk-individuals-often-struggle-to-get-insurance-coverage-of-health-servicesederal

[16] Dean, M., & Rauscher, E. A. (2017). "It was an Emotional Baby": Previvors' Family Planning Decision-Making Styles about Hereditary Breast and Ovarian Cancer Risk. Journal of genetic counseling, 26(6), 1301–1313. https://doi.org/10.1007/s10897-017-0069-8

[17] Boumis, J. K., & Dean, M. (2021, September 20). Understanding BRCA1/2 previvors’ information and support needs: Results from a community needs assessment. FORCE Blog. https://www.facingourrisk.org/blog/understanding-brca1-2-previvors-information-and-support-needs

[18] McGrath, D. (2023, August 1). Few people with cancer undergo testing for inherited gene mutations. Cancer Currents Blog. National Cancer Institute. https://www.cancer.gov/news-events/cancer-currents-blog/2023/germline-testing-cancer