kimberly rohan anp-bc, aocn nurse practitioner edward
TRANSCRIPT
Kimberly Rohan ANP-BC, AOCN Nurse Practitioner
Edward Cancer Center
Objective The nurse will be able to explain biomarkers and their implications to patient’s prescribed treatment plan
Biomarkers Use in Oncology Risk Assessment Diagnosis Prognosis and treatment predictions Pharmacodynamics and
Pharmokinetics Monitoring treatment response Recurrence
Risk Assessment Offer a quantitative way to determine when individuals
are predisposed to particular types of cancers KRAS, p53, erbB2 Colorectal, Esophageal,
Liver and Pancreatic
BRCA1, BRCA2 Breast and Ovarian
Methylation of tumor suppressor genes p16, CDKN2Bm p14ARF
Brain Cancer
Mypermethylation of MYOD1, CDH1 and CDH13
Cervical Cancer
Hypermethylation p16, p14, RB1
Oral Cancer
Diagnosis Ascertain if Primary or Metastatic Tumor Identify tumor type Classify subtype of cancer
Prognosis and treatment predictions/decisions Correlate with good, intermediate or poor survival
outcomes (Veristrat) Guides in decision to pursue stem cell transplantation
or adjuvant chemotherapy (Oncotype Dx) Guides choice of specific drug regimen to utilize
according to tumor molecular genotype or phenotype
Examples Breast ER/PR
HER-2/neu
Colorectal EGFR KRAS UGT1A1
Gastric HER2/neu
GIST c-KIT
Leukemia/Lymphoma CD20 Antigen CD30 FIP1L1-PDGRFalpha PDGFR Philadelphia Chromosome (BCR/ABL) PML/RAR alpha TPMT UGT1A1
Lung ALK EGFR KRAS
Melanoma BRAF
Pharmacodynamics and Pharmacokinetics
Evaluates how a patient will metabolize or change the chemical structure of a drug
Assist in drug dosing Examples:
Thiopurine methyl-transferase (TPMPT) for Mercaptopurine
Dihydropyrimide dehydrogenase (DPD) deficiency for 5-fluorouracil
Monitoring Treatment Response Monitor Response to treatment/therapy
Elimination of BRC-ABL transcript Relapse of disease
CA 125 PSA
Apoptosis Cytochrome c Nucleosomes Cleaved cytokeratin-18 E-cadherin
Melanoma Protein marker – S100-beta
Recurrence Oncotype Dx
Early stage (1 or 2) Node negative ER + Invasive
Panel of 21 genes Recurrence score
Low Intermediate High
When
Diagnosis Relapse Metastatic Disease
Meaning
Urinalysis
Personalized Care
• Surgery • Combination
• Chemotherapy • Targeted
Therapy • Immunotherapy
• Radiation
Tumor Genomics
Performance Status Markers
Cost and Reimbursement Genetic Testing $200-$2000 Molecular Testing Oncotype $4,380 Foundation Medicine Testing Veristrat
Resources http://www.cancer.gov/cancertopics/factsheet/Therap
y/targeted www.cancercare.org www.cancer.org www.nccn.org
http://www.nccn.org/professionals/biomarkers/default.asp
Adjuvant Online Breast Colon Lung
Case Study - Breast 41 year old female Stage IA (T1bN0M0) invasive ductal carcinoma of the right breast grade 3, tumor size was 8 HER-2 non-amplified ER positive at 24% PR negative Ki-67 high at 72%
Genetic Testing Summary and Plan: Ms. B was referred for genetic counseling due to a personal history of breast cancer at age 41. Her family history is not highly suspicious for a hereditary cancer syndrome; however, genetic testing on Ms. B for BRCA1/2 mutations is indicated based on her personal history. At the conclusion of the counseling session Ms. B decided to proceed with BRCA1/2 genetic testing (sequencing and BART). Blood and paperwork were sent to Myriad genetic labs for insurance pre-determination. Myriad handles billing for BRCA1/2 genetic testing. If Ms. B’s responsibility for the cost of genetic testing is more than $375 Myriad will contact Ms. B directly so she can decide if she wishes to proceed with BRCA1/2 testing.
Genetic Testing Results Genetic Testing Result: No mutation was found in the BRCA1 or BRCA2 genes using both comprehensive and BART technology. These results were discussed with Ms. B by phone on 2/20/14. Summary and Plan: These results indicate that it is unlikely that Ms. B has a BRCA1/2 gene mutation. The limitations of the testing were previously discussed with Ms. B including the small chance that a mutation in a gene other than BRCA1/2 might be the cause of cancer in Ms. B. While I do not recommend any additional genetic testing on Ms. B at this time, I encourage Ms. B to contact me on an annual basis to see if there have been any updates in genetic testing that would apply to her or to inform me if there are any changes to the family history.
Discussion I went over her Oncotype Dx results with her and her husband in
detail. We also used the adjuvant online program in our discussion. Her risk of recurrence is high and adjuvant chemotherapy is recommended. Different regimens used were discussed in detail including TC and dose dense AC followed by Taxol (both dose dense and weekly) as well as potential side effects. There was discordance of the Oncotype Dx ER score (which was negative) compared IHC done which was positive @ 24%. I explained to them that results may differ using other methods or reported by other labs. As IHC staining is still considered standard for reporting hormone receptor status, she would still be considered hormone receptor positive (intermediate positive) and a candidate for endocrine therapy.
She had not been keen on pursuing chemotherapy and endocrine therapy but was more open to this after our discussion and wanted some time to think about this further and discuss with her family and friend who is an oncologist. Print outs on the drugs discussed were given to them as well. She has an appointment with the genetics counselor this Thursday. She is aware as she has undergone a lumpectomy that post-op RT will be recommended as well.
Treatment Plan 4 cycles of TC Radiation Hormonal Therapy – Tamoxifen
Case 2 - Lung Final Diagnosis: A, B- EBUS-guided fine needle aspiration, 11R right hilar lymph node, direct smears and cell block preparation: -Suboptimal for evaluation. -Negative for malignant cells. -Specimen consists of predominantly bronchial epithelial cells and blood with only scant lymphoid tissue present within the cell block preparation. C, D- EBUS-guided fine needle aspiration, 7 subcarinal lymph node, direct smears and cell block preparation: -Adequate for evaluation. -POSITIVE for malignant cells. -Consistent with metastatic poorly-differentiated adenocarcinoma.
Immunohistochemical stains do show positive staining for cytokeratin 7, TTF-1, and Napsin-A within the tumor cells. P63 shows background cytoplasmic staining. Immunohistochemical stains for cytokeratin 20 and cytokeratin 5 are negative. Overall, the clinical, cytologic and immunohistochemical findings are most consistent with metastatic poorly-differentiated adenocarcinoma with staining profile consistent with a lung primary.
ALK Result: nuc ish(ALKx2)(3'ALK sep 5'ALKx1)[40/50] 80% of 50 nuclei had a separation of the 3'ALK and 5'ALK signals. The normal cutoff when 50 nuclei are analyzed is <50.0% for one 3'ALK, one 5'ALK and one 3'ALK/5'ALK signal. Interpretation: The result is abnormal and indicates 80% of nuclei had a rearrangement of the ALK locus. Rearrangement of the ALK gene at 2p23 has been observed in a subset of non small Cell lung carcinomas. Lung carcinomas with ALK rearrangements may be sensitive to directed ALK inhibitors.
EGFR No EGFR mutation was detected. This result does not rule out the possibility of a mutation below the detectable limit of the assay.
Discussion She has biopsy proven stage IIIA disease. She has
bulky subcarinal nodes. Standard treatment therefore is definitive concurrent chemoradiation.
She also appears to be EML4-ALK rearrangement positive which will not change her treatment plan for stage IIIA disease at this time.
Treatment Plan Definitive Chemo/RT Follow – if recurrence or progression
Crizotinib
Case – 3 Lymphoma Left deep cervical lymph node, excision: -Follicular lymphoma, low grade, grade 1-2 of 3 (WHO). Immunoperoxidase stains were performed to further evaluate the lymph node. CD3 highlights small lymphocytes within interfollicular regions. CD20 is positive within follicles. Bcl-6 is positive within germinal center cells. Bcl-2 is positive within germinal center B cells. CD21 highlights the follicular dendritic network. Cyclin D1 is negative within the lymphoid infiltrate. Ki-67 is positive in less than 20% of cells. Flow cytometry immunophenotyping was performed on the submitted tissue. Lymphocyte are predominantly B cells. B cells show lambda surface immunoglobulin light chain restriction. The monotypic B cells are CD19 positive, CD20 positive, CD10 positive, and CD5 negative. T cells show no significant antigen deletion with the markers assayed.
Bone Marrow Biopsy Final Diagnosis: Peripheral blood smear, bone marrow aspiration, touch preparation and biopsy: -Focally hypercellular bone marrow showing features consistent with involvement by the patient's previously diagnosed follicular lymphoma. Specimen type: Bone Marrow Reason for referral: Lymphoma Test performed: Chromosome Analysis Laboratory analysis Number of cells counted: 20 Number of cells analyzed: 20 Number of cells karyotyped: 20 ISCN Band level: 375 Banding Method: G-Banding ---------------------------------------------------------- Chromosome results: 46,XX[20]
Treatment Plan Bendamustin/Rituxan
Non-seminoma testicular cancer consistent with stage IS disease (T2, N0, M0, S1): 1/23/2012 AFP, SERUM, TUMOR MARKER: 10.2 (H) Received chemotherapy 2/8/2014 AFP, SERUM, TUMOR MARKER: 2.0 Follow AFP every 3 months
Future- 2030 “For common cancers, multiple targets and their interactions will be understood. Treatment combinations will be tailored to the individual patient's molecular profile” (ASCO, Shaping the Future of Oncology Brochure)
