PHC Scenarios for Clinical Decision Support (CDS)

Breast/Ovarian Cancer

Family history to assess risk: A 30 year old woman schedules a health maintenance examination with her physician. She is asked to provide family history information on how to access the form in a patient portal (personal health record or PHR). She clicks a button indicating a family history of breast cancer. The form asks context-specific prompting questions (what relationship are the affected individuals, age at diagnosis, bilateral disease, family history of other relevant cancersovarian, prostate, etc.). The woman indicates that her mother was diagnosed with breast cancer at age 43, her sister had breast cancer at age 38 and her maternal grandmother died of ovarian cancer at age 60. The program also prompts her to provide her ethnicity which is Ashkenazi Jewish and asks whether anyone in the family has been tested for a gene associated with breast or ovarian cancer to which she replies no. She indicates that she does not have a personal history of breast/ovarian cancer. An algorithm (such as BRCAPRO) calculates the likelihood of a BRCA1 or 2 mutation. The family history she has provided exceeds a defined threshold and a message about increased risk is provided to patient along with educational information that explains her risk and options she has to manage the risk.

Preemptive screening based on elevated risk: Based on a family health history that suggests the patient may be at a higher risk for breast/ovarian cancer, the provider is prompted to order a mammogram, despite the age of the patient, as the evidence-based guideline suggests that mammography should be initiated 10 years prior to the earliest age of cancer onset in the family. The message also notes a strong likelihood of a BRCA mutation. It recommends a referral for genetic counseling. The provider recommends both and the patient chooses to pursue mammography.

Genetic testing to determine treatment options: Following mammography, a suspicious lesion is identified in the left breast. Needle biopsy is suggestive of cancer, so surgery is performed. The lump is removed and the sentinel nodes are negative for breast cancer. Histologic examination shows an adenocarcinoma that is estrogen receptor and Her2-Neu positive. A portion of the tumor is sent for multigene analysis (either OncoType DX or Mammaprint). This analysis provides a low risk estimate for metastatic disease. In anticipation of a multidisciplinary conference to discuss treatment options, the patient has met with a genetic counselor and has agreed to be tested for a BRCA mutation. Given her ethnicity, a test was sent for the three Jewish mutations, rather than full sequencing of BRCA1 and 2. She is found to carry a mutation in BRCA2.

Her2/neu testing for Herceptin treatment: A 50 year old woman presents with locally advanced breast cancer. Before starting the chemotherapy regimen, the physician is prompted to order genetic testing for the Her2/neu gene, which has the largest impact on response to trastuzumab (Herceptin) dose and the patient is sent to the lab. Results indicate that the patient overexpresses Her2/neu. The results are then sent to the clinician, along with a notice to the patient that the results are ready. The clinical team decides that the patient should be put on combination therapy that includes doxorubicin, cyclophosphamide, and paclitaxel supplemented with trastuzumab to treat her breast cancer.

Pharmacogenomics

Anticoagulation therapy: A 75 year old man presents with atrial fibrillation. His cardiologist wishes to start the patient on Warfarin for chronic anticoagulation. He opens the electronic health record (EHR) and goes to the electronic prescribing portal and clicks on Warfarin. The program queries the EHR to obtain information about the patient that affects Warfarin dose (e.g., weight, age, gender, renal function, allergies and other medications that can affect Warfarin metabolism). If some factors are not available, the physician is prompted to supply the information. If the patient has been on Warfarin before, information about the previous stable dose is retrieved. The program then inquires about genetic testing for CYP2C9 and VKORC1, the two genes that have the largest impact on Warfarin dose. If this testing has been done, it is retrieved and the program uses an evidence based algorithm that accounts for all factors to determine a starting dose. If the genotype information is not available, the physician is prompted to order this test and the patient is sent to the lab. When the results are available the clinician is notified and the dose is calculated using the genetic and non-genetic factors.

Chemotherapy for colon cancer: A 50 year old man presents with metastatic colon cancer, and his oncologist begins him on a regimen of fluorouracil (5-FU). However after several courses of treatment, the cancer has not responded to the treatment. The oncologist would like to next try treatment with irinotecan, which has been shown to be effective when 5-FU treatment has failed. The antineoplastic agent, irinotecan (CPT-11), is metabolized by enzymes known to exhibit polymorphic activity. Individuals who are homozygous for the UGT1A*28 allele are at increased risk for neutropenia following initiation of irinotecan treatment. A reduced initial dose should be considered for patients known to be homozygous for the UGT1A*28 allele. Heterozygous patients may be at increased risk of neutropenia; however, clinical results have been variable and such patients have been shown to tolerate normal starting doses. After genetic testing using Genzyme’s UGT1A1 Molecular Invader Assay, the patient is shown to be heterozygous for the UGT1A*28 allele, and therefore at increased risk for neutropenia. After careful discussion between the oncologist and the patient, he begins treatment with the standard dosing regimen, but will be monitored very closely for any neutropenia related toxicity due to his heterozygous status.

HIV Resistance to Anti-retroviral Therapies: A 25 year old woman presents with HIV. Her primary care physician wishes to start the patient on anti-retroviral therapy, but before deciding on a specific pharmaceutical intervention, the physician would like more information about potential resistance of the patient’s strain of the virus to established interventions. The TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System is intended for use in detecting HIV genomic mutations (in the protease and part of the reverse transcriptase regions of HIV) that confer resistance to specific types of anti-retroviral drugs, as an aid in monitoring and treating HIV infection. The physician is prompted to order this test and the patient is sent to the lab. When the testing procedure as completed, the raw results are processed into a clinical finding, and sent to the clinician, along with a notice to the patient that the results are ready. The genotyping on the patient’s particular strain of HIV show that the virus is not resistant to current anti-retroviral therapy. The patient then consults with the clinician regarding these results, and the appropriate anti-retroviral therapy is selected.

Biosurveillance/Screening

Venous Thromboembolism: A 35 year old woman is admitted to the hospital following a cholecystectomy. The hospital operates an active surveillance system to prevent the development of Venous Thromboembolism (VTE). A number of factors are ascertained that can predispose to VTE including family history of VTE, history of cancer, medications (such as oral contraceptives), high-risk injuries or procedures (joint replacement) and two genetic factorsFactor V Leiden (FVL) and the Prothrombin G20210A mutation (PTM). The EHR obtains the information from the patient demographic area, electronic family history, medication list, problem list and the laboratory information system (LIS). The patient has a family history of VTE and she had previously been tested for FVL and PTM. She is heterozygous for the relevant mutation in each of the two genes. Based on the combination of family history and the genetic mutations, she is identified as being at high risk for VTE. The EHR then assesses whether or not VTE prophylaxis has been initiated (compression stockings, early ambulation, low molecular weight heparin, etc.). If it has not the attending physician is notified of the increased risk and is asked to initiate prophylaxis.

Suggested topics for additional scenarios:

Colorectal screening

Newborn screening