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

10 Applying Pharmacogenomics in Therapeutics
who received neoadjuvant chemotherapy with trastuzumab followed by adjuvant
trastuzumab had a higher event-free survival at three years (71% vs. 56%,
p < 0.05) versus patients who were not treated with neoadjuvant trastuzumab. 49
Additionally, patients who received neoadjuvant trastuzumab had a higher pathological
complete response in breast tissue (45% vs. 22%, p < 0.05). 49 These data
are consistent with the results from the GeparQuattro study, where a pathological
complete response was observed with an anthracycline–taxane-based neoadjuvant
chemotherapy with trastuzumab in locally advanced, HER2-positive breast
cancer. 50
Testing Availability and Recommendations
Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), chromogenic
in situ hybridization (CISH), a quantitative HER2 total expression, and
HER2 homodimer assay are several methods for detecting HER2. 51 Although FISH
assesses whether HER2 gene amplification has occurred, IHC evaluates the level of
HER2 protein in invasive breast cancer cells. Combining aspects of FISH and IHC
is CISH, which uses permanent staining and ready identification of invasive tissue to
selectively stain for the HER2 gene. This method has proven to be a better predictor
of HER2-expression status. 51 Although IHC, FISH, and CISH are indirect measures
of the HER2 gene, the HER mark assay provides a quantitative measurement of
HER2 total protein and HER2 homodimer levels. 51,52
Trastuzumab should only be used in patients with HER2-overexpressing
breast cancer. The American Society of Clinical Oncology/College of American
Pathologists recommend that HER2 testing be performed in all patients with invasive
(early stage or recurrence) breast cancer. 53 The National Comprehensive Cancer
Network Task Force Report provides guidelines about IHC and FISH cutoff scores
to determine HER2 status. 52
TOXICITY: ABACAVIR
Clinical Case
A 25-year-old male patient with a six-month history of acquired immunodeficiency
syndrome (AIDS) presents to the clinic today with fever and a maculopapular rash
on the trunk of his body for the past five days. He has no known drug allergies, and
his last viral load was 25,000 copies and CD4 count 110/mm 3 . His current antiretroviral
regimen is abacavir, zidovudine, and efavirenz. He is prescribed with
sulfamethoxazole–trimethoprim for Pneumocystis jiroveci pneumonia prophylaxis.
Background
Abacavir is a nucleoside reverse transcriptase inhibitor used for combination antiretroviral
therapy for treating human immunodeficiency virus (HIV) infections.
Despite its efficacy in treating HIV infections, abacavir has been associated with
treatment-limiting hypersensitivity reaction (HSR). Abacavir-induced HSR occurs