Biomedical Engineering Reference
In-Depth Information
It is increasingly recognized that genomic or molecular basis of
cancer are important to whether a patient with cancer will derive
a greater benefit from a particular treatment. There are more and
more numbers of examples that demonstrate how our improved
understanding of cancer biology may lead to new treatments and
how the selective application of treatments based on the results of
the markers that correlate with greater benefit (Table 1.2). One such
example is the overexpression or amplification of human epidermal
growth receptor 2 (HER2; 3+ by protein or ≥ 2.0 FISH ratio by
gene amplification), which identifies patients who have a poorer
prognosis with standard chemotherapy and also a greater benefit
from anthracycline-based adjuvant chemotherapy (Chapter 4).
American Society of Clinical Oncology (ASCO) recommends that an
anthracycline should be strongly considered for patients with HER2-
positive breast cancer.
10
The recommendation is based on the Level
II evidence, that is, prospective therapeutic trials in which biomarker
utility is a secondary study objective in clinical trials (see Chapter
2).
Level I evidence is referred to as prospective controlled study
that is specifically designed to test marker or evidence from meta-
analysis. Please refer to the publications of Hayes
11,12
et al.
and Simon
11,12
et al.
for the tumor marker utility grading system in detail.
Recently, level II evidence has found that Akt phosphorylation at
Ser473 (pAkt-S473) predicts a disease-free survival benefit from the
addition of paclitaxel to adjuvant doxorubicin plus cyclophosphamide
chemotherapy in node-positive breast cancer.
13
Moreover, growing evidence has suggested that not all patients
derive same magnitude of benefit from chemotherapy in patients
with early stage I and II ER-positive and node-negative breast cancer.
Onco
DX assay developed by Genomic Health, Inc., and the
National Surgical Adjuvant Breast and Bowel Project (NSABP) can
predict a large chemotherapy benefit (specifically the combination
of cyclophosphamide, methotrexate, 5-fluorouracil or CMF regimen)
in patients with high-recurrence score tumors.
type
Patients with low-
recurrence score tumors have an excellent long-term survival with
adjuvant tamoxifen treatment and may not need to receive adjuvant
chemotherapy.
Many genetic factors correlate with the likelihood of severe
and life-threatening drug toxicities. For instance, dihydropyrimine
dehydrogenase (DPD) deficiency predispose patients to
5-fluorouracil (5-FU) toxicity as DPD is the initial and rate-limiting
14
