The Human Genome Project determined the DNA sequence (order of base pairs) of the entire human genome. Humans are 99.9% identical at the level of base pair ordering, but the 0.1% difference contributes to disease risk. Upon completion of the human genetic blueprint, research turned to identifying and cataloguing genomic variation as well as determining the clinical relevance of variants.

On September 4, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pralsetinib (Gavreto™) for adult patients with metastatic, RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.

Patients who watch crime shows think that DNA testing is as simple as taking a cheek swab and getting the results in two minutes so the case is solved at the end of the 42-minute episode. The reality? DNA can be identified from buccal cells in a cheek swab, but results take several weeks to obtain and are not always a simple negative or positive.

Patients approach genetic testing, either for germline (inherited) or somatic (tumor) alterations, hoping it will provide valuable information about their cancer risk, prognosis, or treatment options. Next-generation sequencing makes it possible to test for panels of 40 or more genes simultaneously. By testing more genes, the possibility of finding an actionable, informative result improves, but so does the chance of having a result with one or more variants of unknown clinical significance.

With the massive paradigm shift in cancer therapy to precision medicine, the use of biomarkers and biomarker testing has also rapidly evolved to guide treatment selection. However, the terminology used in genomics is complex and inconsistent, and patient advocacy organizations recommend using a common taxonomy to prevent confusion among patients and providers alike. Nurses spend more time with patients and families than any other member of the healthcare team and can reinforce common language and terminology. As a nurse, here are the terms you need to understand.

Genetics testing is not just about one family member; the results have implications for an entire family. Results of genetic testing can be confusing, and families often need assistance understanding what it means for them. Genetics counseling before and after testing is very important to help individuals and families understand the results of genetic testing when they are received and over time. 

When referring patients for genetics counseling and possible testing for hereditary risk, oncology nurses can help relieve their trepidation and anxiety by explaining what to expect during the visit. See the sidebar for key indications for referral.

Further understanding of the human genome and the proliferation of genetic data has spurred significant advancement in the understanding of the way cancer impacts individuals. To share the crucial work in genetics, the National Institutes of Health (NIH), led by the National Institute for Cancer (NCI), has compiled survivor stories from patients who have benefited from cutting-edge genomic technology. Their stories illustrate and contribute to the ongoing successes brought on by NIH’s genomic efforts.

Although most cancers contain four to five driver mutations, those drivers remain unknown for about 5% of cancers, according to results of a series of studies examining genomes from 38 different cancer types. The international Pan-Cancer Analysis of Whole Genomes Consortium reported the findings in a collection of 23 articles published in Nature and other affiliated journals.

Genomic testing identifies germline or inherited DNA changes that increase a person’s cancer risk, and it also can identify or profile the somatic or acquired changes in a tumor that guide selection of appropriate targeted therapies. The latter type of genomic testing is an analysis of DNA sequence information.

Cancer occurs from mutations, or harmful changes from an alteration in a gene’s DNA sequence. Most mutations involve changes in the order of the base pairs, including substitutions, deletions, additions, or shifts. Mutations can be divided into broad categories based on the tissue where they occur.

According to findings from a new analysis published in JAMA Oncology, multigene testing should be expanded to all women with breast cancer and not just those with certain family histories or clinical factors.

Genetics versus genomics: Is there a difference? Does it even matter? There is, and it does. In our era of precision medicine, also referred to as individualized or genomic medicine, being able to differentiate the terms is a first step in establishing a foundational understanding of what they mean for cancer care from prevention to treatment.

Precision medicine has a been a hot topic in health care for years now, but costs and coverage issues have created challenges to get patients the genetic testing they need at an affordable cost. In a memo from October 29, 2019, the Centers for Medicare and Medicaid Services (CMS) proposed extending Medicare coverage to pay for genetic sequencing tests for certain hereditary types of ovarian and breast cancer.

On August 15, 2019, the U.S. Food and Drug Administration (FDA) granted accelerated approval to entrectinib (Rozlytrek^TM) for adults and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy.

During the  44th Annual ONS Congress in April 2019, some sessions featured a Continuing the Conversation event following the main session. As a speaker, this might have been the best part for me. It was filled with unexpected, wonderful surprises and great conversations with oncology nursing colleagues.

As part of the rising wave of precision medicine initiatives, the National Institutes of Health (NIH) launched the All of Us campaign in 2018. This one-of-a-kind research program aimed to collect data from more than one million Americans, including factors about lifestyle, environment, and biology, to understand impacts on health and well being. The information would help researchers to better understand the individual nature of health to ultimately inform decisions about delivering precision medicine.  

The future of cancer care is here: precision medicine has led to many of today’s newest cancer treatments and has made incredible progress since former President Barak Obama first announced the U.S. Precision Medicine Initiative (PMI) in 2015.

After recent a best-selling book-turned-movie detailed her story, Henrietta Lacks’ extraordinary impact on cancer research continues to become common knowledge to more people. However, many more are still unaware of how her story, struggle with cancer, and tumor cells changed the face of cancer care. For that reason, Representative Elijah Cummings (D-MD), along with a congressional delegation from both chambers, introduced legislation to both honor her role in history and improve access to medical research to traditionally underrepresented groups.

As genetic and genomic testing become more common—and complex—in cancer diagnosis and treatment decisions, more efficient and accessible ways of providing comprehensive genetic care are needed. In their article in the February 2019 issue of the Clinical Journal of Oncology Nursing, Pierle and Mahon discussed the findings from their literature review, specifically pertaining to genetics care services across the cancer continuum, patient and system barriers to accessing care, new service delivery models, and oncology nurses’ role in providing comprehensive cancer genetics care services.

According to researchers, only 43.8% of positive genetic variants detected in men with prostate cancer had corresponding recommendations for germline testing in National Comprehensive Cancer Network (NCCN) guidelines. The findings were published in JAMA Oncology.

Eighteen months after completing surgical debulking and chemotherapy for stage III high-grade serous ovarian cancer, 56-year-old Lily experienced a rising CA-125 level. At her oncologist’s recommendation, Lily started an aromatase inhibitor, but it did not stop the rising tumor marker. After she began experiencing symptoms of bloating and mild abdominal pain, Lily and her oncologist decided to proceed with second-line chemotherapy. As she left the office, Lily remarked that she did not complete genetic testing when she was originally diagnosed because she does not have any children or a family history of ovarian cancer and she was concerned that her insurance would not cover the testing.

New treatment options continue to emerge for diseases that until recently had limited, if any, treatment choices. Nurses are seeing more changes in the way treatment regimens come together, biosimilars are presenting viable options for patients, and genetic mutations, as opposed to disease sites, are at the forefront of drug development.  

Underserved communities largely have low rates of cancer genetic testing. Although the reasons vary, they can include lack of referrals, no or underinsurance, prohibitive cost, lack of trust, lack of knowledge, discrimination issues, or competing health needs.

Genomic testing—identifying variants, like mutations, in tumor cells to inform patient treatment options—occasionally comes with unanticipated results that clinicians have to address with their patients. Clinicians and patients alike are often hopeful that tumor genomic testing will identify a personalized cancer treatment. Indeed, many patients have benefited from being candidates for new targeted therapies identified through genomic testing. 

Every cancer diagnosis is as individualized and unique as the person receiving it. From family history to societal and economic background to a patient’s genetic make-up and composition, cancer affects each person with cancer differently. Initiatives like precision medicine are based in data that suggest that a personalized disease should have its own personalized treatment. As a subset of precision medicine, precision oncology assesses a patient’s unique genetic profile to help align targeted therapies to hit the right cancer subtypes. 

An S5 methylation test detected 100% of grade 2 cervical intraepithelial neoplasms or worse, compared to a 50% detection rate for Pap or human papillomavirus (HPV) tests, according to the results of a recent study reported in the International Journal of Cancer.

Multigene testing for hereditary breast and ovarian cancer has increased the detection predisposition genes beyond BRCA1 and BRCA2, according to study findings presented at the San Antonio Breast Cancer Symposium on December 7, 2018. 

On November 26, 2018, the U.S. Food and Drug Administration (FDA) granted accelerated approval to larotrectinib for adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, that are either metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or whose cancer has progressed following treatment.

Which Gene is Associated With Cowden Syndrome (Multiple Hamartoma Syndrome)?

A. APC 

B. VHL 

C. TP53 

D. PTEN

As researchers learn more about how combination therapy combats drug resistance and lessens the changes of tumor evasion of the immune system, immune checkpoint inhibitors are receiving approval for a broader range of indications. However, recent U.S. Food and Drug Administration (FDA) approvals have centered around hematologic malignancies and the emergence of two new biosimilars. 

My story, like many of your patients, is unfortunately not that uncommon: I’m a motherless daughter. I lost my mom to breast cancer when I was 26 years old; she lost her mother to the disease before she graduated high school. The BRCA1 mutation has been passed down in my family, and I, too, carry the mutation. Even though it was expected, I was devastated and desperately looking for resources to help manage my cancer risk. It was scary not knowing where to turn. I needed to know that I wasn’t alone. 

Radiation therapy can be an incredibly draining form of treatment for patients with cancer. Side effects such as fatigue can be debilitating for many before, during, and after treatment. Because symptom management is a crucial component to cancer care and central role of oncology nursing, ensuring that patients are able to mitigate their symptoms and side effects can help improve their quality of life. Recently, a team at the National Institute of Nursing Research (NINR) identified certain genes associated with fatigue in men being treated for prostate cancer.

On March 6, 2018, 23andMe—an at-home genetic testing company—announced their direct-to-consumer genetic test (DTCGT) would include DNA results for the three common founder BRCA mutations commonly seen in people with Ashkenazi Jewish ancestry. This was big news because DNA results for the BRCA mutations had been previously available on the 23andMe panel report until the U.S. Food and Drug Administration removed them in 2013.

Researchers have developed two new gene-based tests that detect DNA mutations that lead to bladder, endometrial, and ovarian cancers. The tests, which are not yet U.S. Food and Drug Administration approved, could be used to identify a new or relapsed cancer earlier, when it is easier to treat.

Although all cancers have a genetic basis, a subset result from an inherited (i.e., germline) mutation that puts a person at increased risk for certain cancers. Unfortunately, the signs of hereditary cancer are often overlooked or misunderstood. Here’s what oncology nurses need to know about BRCA mutations, one of the more common mutations you’ll see in practice.

Which Genetic Test Performed on Tumor Cells Has Prognostic and Predictive Uses? 

A. BRCA1 test 

B. CA 27.29 

C. Circulating tumor cells

D. Oncotype DX^® 

With hopes for more than 1 million participants, the National Institutes of Health (NIH) has launched the All of Us initiative, a radical precision medicine campaign to amass a collective gene pool data repository. The NIH is aiming to shrink our differences and expand on the similarities found in our genetic data. For some, compiling genetic data of an entire country’s citizens may sound very reminiscent of Big Brother from the book 1984. But the amount of information that could be shared and learned from such a massive health database is remarkable.

On April 30, 2018, the U.S. Food and Drug Administration (FDA) granted regular approval to dabrafenib (Tafinlar ^®) and trametinib (Mekinist^®) in combination for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.

Which of the following is gene that may play a role in tumor resistance to chemotherapy?

A. NRAS

B. APC

C. p53

D. VHL

April 25, 2018, marks National DNA Day. Why the hype? National DNA Day commemorates the successful completion of the Human Genome Project in 2003, and the discovery of DNA's double helix in 1953. Without DNA, understanding the diseases and treatments for cancer would be nearly impossible. Genetics and genomics play huge roles in treating malignancy, and it’s crucial to the care of patients with cancer for oncology nurses to understand genetics and genomics.

An international survey of 86 genetic testing labs showed inconsistent protocols and standards for analyzing the BRCA1 or 2 cancer susceptibility genes and their variations. The results were reported in NPJ Genomic Medicine.

Researchers for the PanCancer Atlas, a genomic data set reference tool, recently completed an analysis of molecular and clinical information from more than 10,000 different tumors spanning more than 33 cancer types. The PanCancer Atlas is the result of nearly a decade’s worth of work associated with the Cancer Genome Atlas—a multi-institutional program driven by the National Human Genome Research Institute and the National Cancer Institute (NCI). The results of the analysis were published as a set of 27 papers.