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Commentary

Shifting to a Biomarker Paradigm Across Cancer Care

Suzanne M. Mahon
CJON 2020, 24(6), 633-634 DOI: 10.1188/20.CJON.633-634

Precision medicine has revolutionized multiple facets of care across the cancer trajectory, from prevention through treatment. Sometimes referred to as personalized medicine, precision medicine uses information contained in an individual’s genes, as well as biomarkers and genetic alterations detected in tumor cells, to prevent, diagnose, and treat malignancy. It can provide valuable information about an individual’s risk for developing malignancy, facilitate an accurate diagnosis, inform or revise a plan of treatment, or offer information about prognosis.

Precision medicine has revolutionized multiple facets of care across the cancer trajectory, from prevention through treatment. Sometimes referred to as personalized medicine, precision medicine uses information contained in an individual’s genes, as well as biomarkers and genetic alterations detected in tumor cells, to prevent, diagnose, and treat malignancy. It can provide valuable information about an individual’s risk for developing malignancy, facilitate an accurate diagnosis, inform or revise a plan of treatment, or offer information about prognosis.

Pathogenesis

The foundation for personalized medicine starts with an understanding of pathogenesis. Cancer is caused by changes in DNA. Harmful alterations in DNA, referred to as pathogenic variants (formerly known as mutations) can affect how cells grow, divide, and function. Somatic, or acquired, pathogenic variants are the most common cause of cancer and may be induced by a variety of carcinogens, including tobacco use, ultraviolet radiation, chemical exposures, and aging. Somatic pathogenic variants are not found in every cell in the body, and they are not passed from parent to child.

Germline pathogenic variants are far less common and are associated with a hereditary predisposition toward developing cancer. The error occurs in either the egg cell or sperm cell, and it is passed directly at conception from a parent to a child. As the embryo develops into a fetus, the error from the initial egg cell or sperm cell is copied into every cell in the body. Because the pathogenic variant affects reproductive cells, it can be passed from generation to generation.

Each individual tumor has a unique combination of genetic alterations. Some of these changes may be the result of additional errors that occur as cancer cells divide, rather than the initiating event that led to the malignancy. Even within the same tumor and over time, cancer cells may have different and evolving genetic changes (Forman & Sotelo, 2019).

DNA sequencing techniques can identify germline and somatic pathogenic variants by comparing the sequence of DNA to sequencing in normal cells. To test for germline pathogenic variants, typically saliva or blood samples are evaluated. Acquired pathogenic variants, which drive tumor growth, are identified with biomarker testing of the tumor. Because new pathogenic variants can develop, repeat tumor sample testing may be warranted to confirm pathogenic variants. As an alternative to tumor specimen biopsies, liquid (blood product) biopsies may be used, particularly when tissue biopsies are not feasible. Liquid biopsies detect alterations in circulating tumor DNA, or small fragments of DNA released by malignant lesions.

Personalized Medicine and Oncology Care

Personalized medicine is not new in cancer care. In 1977, the U.S. Food and Drug Administration (FDA) approved tamoxifen as an adjuvant therapy for postmenopausal women with estrogen-driven breast cancer (Lukong, 2017). More than 40 years later, tamoxifen is still a personalized treatment used in all stages of estrogen receptor–positive breast cancers. It is an example of an early biomarker-driven treatment.

In 1998, trastuzumab and an immunohistochemistry assay for HER2 expression received approval by the FDA as a combined diagnostic drug tool (a biomarker assay that determines if a specific therapy will be effective, which must be used to prescribe the drug) to select treatment in breast cancer (Lukong, 2017). Tumors with HER2 expression can now be treated with trastuzumab, pertuzumab, lapatinib, and neratinib (National Comprehensive Cancer Network, 2020).

In 2004, Genomic Health released the Oncotype DX® Breast Cancer Assay to help guide decisions on whether the addition of chemotherapy is beneficial in women with early-stage breast cancer (Lukong, 2017). This assay analyzes 21 genes in a breast tumor with reverse transcriptase polymerase chain reaction to predict chemotherapy benefit, as well as the probability of recurrence and survival within 10 years of diagnosis. This is an example of a predictive biomarker; it helps identify individuals who may benefit—or not benefit—from specific treatments. The Oncotype DX Breast Cancer Assay also serves as a prognostic biomarker, identifying the likelihood of a clinical event, such as disease recurrence or progression.

As of November 2020, there are more than 70 FDA-approved targeted agents for the treatment of solid and hematologic malignancies based on biomarkers detected in the tumor (Abramson, 2018). The number of agents will continue to grow.

There is an emerging convergence of germline testing and tumor testing. For example, the relevance of germline BRCA1/2 pathogenic variants drives decisions about cancer prevention and early detection, including the possibility of risk-reducing surgery in individuals at an elevated risk for developing cancer. Germline and acquired pathogenic variants also provide insight into the efficacy of poly(ADP-ribose) polymerase inhibitor therapy in patients with breast, ovarian, or pancreatic cancer (Alldredge & Randall, 2019). Germline pathogenic variants can also be predictive biomarkers. For example, men with prostate cancer who carry pathogenic germline variants in BRCA2 and who are undergoing hormonal therapy are 27 times more likely to experience failure with hormonal therapy and progress to metastatic disease (AlDubayan, 2019).

A recent development in personalized medicine is tumor-agnostic, biomarker-driven therapy. A tumor-agnostic treatment involves an agent that treats any kind of cancer with a specific biomarker, regardless of the primary site (Yan & Zhang, 2018). Historically, most cancer treatments targeted a specific organ. Pembrolizumab was the first treatment approved for adults and children with microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (MMRd) metastatic tumors regardless of the organ site. MSI-H or MMRd tumors have difficulty repairing DNA damage and often develop large numbers of alterations in their DNA, which produce abnormal proteins that disrupt cellular function, leading to malignancy development.

Specific Cancer Diagnoses and Genetic Testing

In this issue of the Clinical Journal of Oncology Nursing, three articles feature a specific cancer diagnosis and the role of genomic biomarkers in supporting clinical decision making and establishing treatment plans. Martin (2020) provides an update about biomarker testing in lung cancer and associated targeted treatment options. For colorectal cancer, Schmitt (2020) reviews cellular signaling pathways and how molecular biomarkers guide treatment decisions. For advanced cutaneous melanoma, Friend (2020) reviews various biomarkers and their role in guiding treatment. In addition to this issue’s three diagnosis-specific review articles, the Genetics & Genomics department focuses on how tumor genomic testing can provide information not only about what might be the best treatment for a malignancy but also the potential germline risk for developing a malignancy (Mahon, 2020).

The Future

For all patients diagnosed with a malignancy, biomarker profiling is becoming a standard of care (El-Deiry et al., 2019). This profiling provides a more robust framework to determine risks associated with an individual’s malignancy and strategies for early detection. In addition, profiling can provide clinicians with clarity about potentially effective treatments, combination treatments, and treatment resistance, as well as offer a foundation for understanding prognosis. New agents and combination agent protocols are being approved based on biomarker testing results instead of the tumor site of origin. It is time to rethink how biomarker testing drives cancer care across the trajectory. This is the new paradigm in cancer care. The time has arrived.

About the Author(s)

Suzanne M. Mahon, DNS, RN, AOCN®, AGN-BC, FAAN, is a professor in the Department of Internal Medicine in the Division of Hematology/Oncology and a professor of adult nursing in the School of Nursing, both at Saint Louis University in Missouri. The author takes full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. Mahon can be reached at suzanne.mahon@health.slu.edu, with copy to CJONEditor@ons.org.

 

References 

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Alldredge, J., & Randall, L. (2019). Germline and somatic tumor testing in gynecologic cancer care. Obstetrics and Gynecology Clinics of North America, 46(1), 37–53. https://doi.org/10.1016/j.ogc.2018.09.003

El-Deiry, W.S., Goldberg, R.M., Lenz, H.-J., Shields, A.F., Gibney, G.T., Tan, A.R., . . . Marshall, J.L. (2019). The current state of molecular testing in the treatment of patients with solid tumors, 2019. CA: A Cancer Journal for Clinicians, 69(4), 305–343. https://doi.org/10.3322/caac.21560

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Martin, J.C. (2020). Genetic biomarkers: Implications of increased understanding and identification in lung cancer management. Clinical Journal of Oncology Nursing, 24(6), 648–656. https://doi.org/10.1188/20.CJON.648-656

National Comprehensive Cancer Network. (2020). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Breast cancer [v.6.2020]. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

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