301characterization of CTCs could contribute to personalized treatment selection
(Toss et al. 2014 ).
A clinical study has used CellSearch™ (Veridex) to prospectively assess CTC
status at baseline and after one cycle of a new line of systemic therapy, as well as
changes from baseline for their utility in predicting response, progression-free and
overall survival in metastatic breast cancer (Wallwiener et al. 2014 ). Increase of
CTCs was signifi cantly associated with progressive disease. Analysis of data
revealed that prognostic factors for shorter progression free survival included per-
sistent CTCs after one cycle, > = 3rd-line therapy, and triple-negative receptor sta-
tus. Presence of bone-and-visceral/local metastases in addition to these was
associated with shorter overall survival. Thus, serial monitoring of CTC number is
useful for determining prognosis and tailoring systemic treatment of metastatic
breast cancer.
Pharmacogenetics of Breast Cancer
Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of
tamoxifen metabolites. CYP450 2D6 and CYP3A5 genotype were determined from
paraffi n-embedded tumor samples and buccal cells (living patients) in tamoxifen-
treated women enrolled onto a North Central Cancer Treatment Group adjuvant
breast cancer trial (Goetz et al. 2005 ). In tamoxifen-treated patients, women with
the CYP2D6 4/4 genotype tend to have a higher risk of disease relapse and a
lower incidence of hot fl ashes.
Proteomics-Based Personalized Management of Breast Cancer
Nipple aspirate protein samples were taken from invasive ductal breast carcinoma
and also had an apparently normal contralateral breast. These can be examined by
2D GE and mass spectrometry as well as highly sensitive staining techniques that
can detect proteins in the picogram range. Among the differential expression pat-
terns of ductal fl uid proteins, some evidence of known and possibly new biomarkers
and drug targets for breast cancer has been observed. The patient-to-patient vari-
ability of these differences may refl ect variables in the disease structure and may
prove to be of clinical diagnostic and therapeutic signifi cance to individual patients.
For example, the presence or absence of known biomarkers detected in the differ-
ences in the fl uids can be used to determine the aggressiveness of the cancer (e.g.
the presence or level of Cyclin E) or signal the appearance of a cancer-related
genetic instability or hereditary component (e.g. the absence or level of BRCA1).
However, this approach requires clinical trials for comparison with the gold stan-
dards such as mammograms, ultrasound, biopsy, nipple lavage and aspirate cytol-
ogy, and serum biomarkers. The presence of known drug targets detected in the
differences in the fl uids may also be used in the future to indicate what drugs to use.
Personalized Management of Cancers of Various Organs