Textbook of Personalized Medicine - Second Edition [2015]

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targeted to chromosome 17 and the HER2/TOP2 amplicon (Yeh et al. 2009 ). Results
were 97 % concordant for HER2 status, meeting the College of American
Pathologists/American Society of Clinical Oncology’s validation requirements for
HER2 testing. No case of complete polysomy 17 was detected even though multiple
breast cancer cases showed polysomies of other chromosomes. Therefore, aCGH is
an accurate and objective DNA-based alternative for clinical evaluation of HER2
gene copy number, and that polysomy 17 is a rare event in breast cancer. It is com-
mercially available as HerScan™ (Combimatrix Molecular Diagnostics).


HER2/neu-Derived Peptide Vaccine for Breast Cancer


HER2-positive breast cancers, which contain more receptors than is typical, are
found in 20–30 % of all breast cancer patients, are treated by trastuzumab and lapa-
tinib that latch on to these receptors and destroy them. However, some of these
patients develop resistance to these therapies or develop cancer metastasis, which
are hard to treat. Vaccination is an attractive alternative approach to provide HER-2/
neu-specifi c antibodies and may in addition concomitantly stimulate HER2-reactive
T-cells. A pilot clinical trial has shown that that HER2-pDNA vaccination in con-
junction with granulocyte-macrophage colony-stimulating factor (GM-CSF) and
interleukin-2 administration is safe, well tolerated and can induce long-lasting cel-
lular and humoral immune responses against HER2 in patients with advanced breast
cancer (Norell et al. 2010 ).
HER2/neu, a source of immunogenic peptides, is expressed in >75 % of breast
cancer patients. Clinical trials have been conducted with the HER2/neu E75 peptide
vaccine in breast cancer patients. Results show that most patients with various levels
of HER2/neu expression respond immunologically and seem to benefi t from vac-
cination (Benavides et al. 2009 ). E75 is predicted to bind to HLA-A3, and preclini-
cal data support this. Another trial has demonstrated that HLA-A3 patients respond
similarly to E75 vaccination as HLA-A2 patients, suggesting the potential use of the
E75 vaccine in up to 76 % of the population (Patil et al. 2010 ). Antigen Express is
developing a peptide immunotherapeutic for in patients with HER-2/neu positive
breast cancer, which is currently in phase II clinical trials.


Molecular Diagnostics in Breast Cancer


Molecular diagnosis of breast cancer is discussed in detail in another report (Jain
2015 ). Some of the tests that relevant to prognosis and personalized
management are:


BRACAnalysis (Myriad Genetics Inc) This test for hereditary breast and ovarian
cancers incorporates thorough full-sequence analysis for gene mutation detection.
Myriad and others have discovered and published information on an additional type
of mutation, known as a large rearrangement that has not been detectable by


Personalized Management of Cancers of Various Organs

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