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indicator that a sample contains insuffi cient tumor cells to make a molecular
diagnosis and that a new sample needs to be taken.
The genetic test was highly sensitive and very predictive for chemotherapy
response. The test was more predictive than typically used clinical molecular mark-
ers such as estrogen receptor status, progesterone receptor status or HER2 gene
expression status. Luminal A was found to be not sensitive to the chemotherapy,
suggesting that patients with this good-prognosis type can forgo chemotherapy in
favor of hormone-based therapy. Among the poor-prognosis tumor types, basal-like
breast cancer was the most sensitive to the chemotherapy and luminal B the least.
Diagnosis by intrinsic subtype adds signifi cant prognostic and predictive infor-
mation to standard parameters for patients with breast cancer. The prognostic prop-
erties of the continuous risk score will be of value for the personalized management
of node-negative breast cancers. The subtypes and risk score can also be used to
assess the likelihood of effi cacy from neoadjuvant chemotherapy. This new genomic
test is broadly applicable for all women diagnosed with breast cancer. Their 50-gene
set can be assayed in preserved tumor samples left over from standard diagnostic
procedures, so that tumor samples from breast cancer cases going back a decade or
more can be studied. Since the patients in these cases have already been treated, the
researchers can quickly discover how well various therapies worked for each breast
cancer type. The genomic test technology will be distributed through University
Genomics, a company co-owned by Washington University, the University of Utah
and the University of North Carolina.
Subtyping Breast Cancer to Predict Response to Chemotherapy Breast cancers
are comprised of molecularly distinct subtypes that may respond differently to
pathway- targeted therapies now under development. Collections of breast cancer
cell lines mirror many of the molecular subtypes and pathways found in tumors,
suggesting that treatment of cell lines with candidate therapeutic compounds can
guide identifi cation of associations between molecular subtypes, pathways, and
drug response (Heiser et al. 2012 ). In a test of 77 therapeutic compounds, the authors
found that nearly all drugs showed differential responses across these cell lines, and
approximately one third showed subtype-, pathway-, and/or genomic aberration-
specifi c responses. These observations suggest mechanisms of response and resis-
tance and may facilitate efforts to develop molecular assays that predict clinical
response.
Prediction of Resistance to Chemotherapy in Breast Cancer
It is well known that some breast tumors acquire altered genes or chromosomes dur-
ing the course of treatment that make them resistant to many cancer drugs. With a
few exceptions, e.g. ER-sensitive HER2-positive cancer, no tests are done before
treatment begins to predict who is going to be resistant or sensitive to chemotherapy.
Most breast cancer patients are initially given the same drugs. In search of genetic
alterations that might explain disease recurrence despite treatment with adjuvant
10 Personalized Therapy of Cancer