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Despite recent advances in breast cancer therapy, women with similar types of
breast cancers may respond very differently to standard treatments. The emerging
fi eld of clinical proteomics has the potential to revolutionize breast cancer therapy.
The ultimate goal of clinical proteomics is to characterize information fl ow through
protein cascades for individual patients. After the protein networks have been elu-
cidated, drug therapies may be specially designed for each patient. Proteomic
technologies of laser-capture microdissection (LCM) and reverse-phase protein
arrays (RPPAs) enable scientists to analyze relative abundances of key cellular
signaling proteins from pure cell populations. Cell survival and apoptotic protein
pathways are currently being monitored with LCM and RPPAs at the NIH in phase
II clinical trials of metastatic breast and ovarian cancers. Ultimately, proteomics
will become an integral component of tracking and managing personalized breast
cancer therapy.
Predicting Response to Chemotherapy in Breast Cancer
Breast cancer patients have benefi ted from the use of targeted therapies directed at
specifi c molecular alterations. Some of the methods used to identify various path-
ways or overexpression of some genes for predicting response to therapy are:
Predicting Response to Trastuzumab Treatment Trastuzumab (TCH) is active
against the overexpressed HER2 oncogene in breast cancer, and several prospective,
randomized trials have shown that adjuvant TCH substantially reduces rates of
recurrence and death in patients with early-stage disease. Combined therapy of
TCH with anthracycline (AC-T)-based regimens has been associated with cardiac
toxicity. A randomized trial showed that addition of 1 year of adjuvant TCH signifi -
cantly improved disease-free and overall survival among women with HER2-
positive breast cancer (Slamon et al. 2011 ). The risk-benefi t ratio favored the
nonanthracycline TCH regimen over AC-T plus TCG, given its similar effi cacy,
fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia.
A DNA probe for the HER2 gene is used to predict whether a breast cancer
patient is a candidate for TCH treatment. Current medical practice requires that all
patients who are considered for TCH treatment be tested for HER2 amplifi cation or
overexpression. SPOT-Light ® HER2 CISH Kit (Life Technologies), which is
approved by the FDA, is based on chromogenic in situ hybridization (CISH), where
results are visualized under a standard bright-fi eld microscope, as opposed to FISH
tests, in which the results must be visualized using a fl uorescent microscope. This
specialized microscope frequently requires that the analysis is done at a reference
lab. In addition, HER2 CISH test results are quantifi able; removing the subjectivity
inherent in tests based on immunohistochemistry.
Genomic Predictor of Response to Taxane-Anthracycline Chemotherapy A
prospective multicenter study was conducted to test genomic predictors for chemo-
therapy containing sequential taxane and anthracycline-based regimens in patients
with newly diagnosed ERBB2 (HER2 or HER2/neu)-negative breast cancer (Hatzis
10 Personalized Therapy of Cancer