Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

8 Applying Pharmacogenomics in Therapeutics
were 71.8% (28/39), 80.3% (49/61), and 90% (18/20) in homozygous EMs, heterozygous
EMs, and PMs, respectively, with no difference based on CYP2C19 genotype
(p = 0.252; Table 1.1). 8
Testing Availability and Recommendations
One genotyping test has been approved by the US Food and Drug Administration
(FDA) and is commercially available (AmpliChip CYP450, Roche Diagnostics;
www.roche.com) for CYP2C19 genotyping. This test requires a whole blood sample,
whereby DNA is extracted and then tested by a PCR-based microarray that
analyzes the presence or absence of CYP2C19*2 and *3 alleles. There are currently
no CYP2C19 testing recommendations for omeprazole. The clinical pharmacology
and drug–drug interaction sections in the prescribing information have been
revised regarding CYP2C19 PMs, but no recommendations for CYP2C19 testing are
documented. 37 Proton-pump inhibitor (PPI) use in patients who are on antiplatelet
therapy 38 have prompted professional organizations to publish expert consensus
statements. For managing therapy with thienopyridines and PPIs, the ACCF/ACG/
AHA states that CYP2C19 testing has “not yet been established.” 39
EFFICACY: TRASTUZUMAB
Clinical Case
JJ is a 58-year-old female who has just been diagnosed with Stage II breast cancer
after first noticing a “hard lump” during a breast self-examination. A mammogram
and ultrasound revealed a 3-cm mass. A biopsy was performed, which revealed
evidence of invasive ductal carcinoma in the right breast and axillary lymph nodes.
A CT scan showed no evidence of metastatic disease. JJ has no first-degree relatives
with breast cancer or other family members affected by early breast cancer. The
plan for JJ is a lumpectomy with complete axillary node dissection, start dose-dense
doxorubicin and cyclophosphamide (“AC regimen”) with a taxane, and possibly
trastuzumab thereafter. However, tumor marker results regarding estrogen receptor,
progesterone receptor, and human epidermal growth factor receptor type 2 (HER2)
statuses are pending.
Background
Trastuzumab is a humanized monoclonal antibody that binds to the extracellular
domain of HER2 and inhibits the proliferation and survival of HER2-dependent
tumors. 40,41 The significance of HER2 in cancers was discovered in the 1980s when
the rodent homolog neu was identified in a rat tumorigenesis model. 42 Trastuzumab
is indicated for HER2-overexpressing metastatic breast cancer, as adjuvant treatment
of HER2-overexpressing early breast cancer in combination with chemotherapy,
and for treatment of HER2-overexpressing metastatic gastric or gastroesophageal
junction adenocarcinoma in combination with cisplatin and 5-fluorouracil or
capecitabine.