Individualizing Colorectal Cancer Care through Genetics

July/August 2010, Vol 1, No 3 - Annual ONS Congress

San Diego, CA—Three nurse researchers from the Oncology Nursing Society (ONS) Cancer Genetics Special Interest Group shared how the results of genetic testing conducted within the care setting are individualizing—and improving—care for colorectal cancer (CRC) at a session at the Annual ONS Congress.

Beginning with an overview of the carcinogenesis of CRC, Carol Viele, RN, MS, a clinical nurse specialist at the University of California San Francisco (UCSF) Medical Center, detailed both its modifiable and non-modifiable risk factors. She stated that even though keeping good health habits, such as exercising regularly, avoiding tobacco, and minimizing alcohol use, can greatly reduce one’s CRC risk, other risk factors, such as advancing age, family history, and genetics, cannot be controlled. By accepting this latter fact, however, and learning more about patients’ genetic make-up, Ms Viele and the other presenters illustrated that healthcare professionals are improving patients’ prognosis, reducing treatment toxicity, and saving cost.

Karen Roesser, RN, MSN, oncology clinical nurse specialist at CIW Medical Center in Richmond, VA, detailed that by determining whether CRC patients have a genetic mutation leading to Lynch syndrome, clinicians can more actively screen for other cancers that are associated with the condition (including endometrial, ovarian, and stomach). Clinicians have been using certain tests, including microsatellite instability testing and immunohistochemistry testing, to better determine which patients may have the syndrome and should undergo further genetic testing.

The session’s third presenter most directly addressed how clinicians are individualizing CRC care in clinical practice. Pamela Viale, RN, MS, CS, ANP, an oncology nurse practitioner also practicing at UCSF, discussed several genetic mutations and how they impact decisions made in CRC care. Beginning with perhaps the most well known, Ms Viale explained that approximately 40% of CRC patients have a mutated KRAS gene that makes treatment with certain monoclonal antibodies unsuccessful. Specifically, the mutated KRAS gene means that 2 important drugs—panitumumab and cetuximab—used to target the epidermal growth factor receptor (EGFR) are ineffective in turning off the cell signaling system and limiting tumor growth. As a result, Ms Viale noted that practitioners must determine early on if a patient has the KRAS mutation to avoid treating the patient with ineffective drugs. She added that both the National Comprehensive Cancer Network (NCCN) guidelines and the American Society of Clinical Oncology professional opinion statement call for KRAS testing before beginning therapy with monoclonal antibodies. Similarly, Ms Viale noted that patients with the BRAF mutation have also shown to be unresponsive to anti-EGFR monoclonal antibodies and that the NCCN now recognizes testing for this mutation as a prudent treatment decision.

Ms Viale also covered findings pertaining to TP 53, a tumor suppressor gene that plays an important role in the growth and differentiation of CRC. Between 40% and 60% of CRC patients have the mutation, and its existence may help practitioners provide a more accurate prognosis. According to Ms Viale, one study found that patients with a mutated TP 53 have a poorer prognosis than those without in both stage II and stage III CRC when treated with surgery alone. Additionally, data have shown that TP 53 inhibits the body’s response to 5-fluorouracil therapy, although conflicting data have also surfaced.

In addition, Ms Viale also detailed how genetic information can reduce toxicity. The UGT1A1 enzyme inactivates the metabolite of the chemotherapy agent irinotecan. Patients with Gilbert syndrome, however, have decreased efficiency of UGT1A1, making them unable to adequately metabolize the drug and leading to increased neutropenia and diarrhea.

Ms Viale provided statistics from a survey conducted at the NCCN 2010 meeting on the prevalence of genetic testing in the treatment of CRC. Responses revealed that 51% of respondents test for the KRAS mutation before therapy is initiated, whereas 37% test for the mutation only when considering treatment with an anti-EGFR monoclonal antibody. Ten percent tested for an alteration of UGT1A1, 16% tested for UGT1A1 only after already treating the patient with irinotecan and experiencing problems, and 63% conducted no UGT1A1 testing. Thus, although the data showed that it is “standard practice now to test for the KRAS mutation,” the numbers revealed fewer clinicians are utilizing information from UGT1A1 tests.