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distinct gene expression profi les and clinical features, and they comprise the
majority of BRCA1-associated tumors. Global gene expression profi ling has uncov-
ered previously unrecognized subsets of human breast cancer, including the “triple-
negative” or “basal-like” subset characterized by a lack of ER and progesterone
receptor (PR) expression, the absence of HER2 amplifi cation, and the expression of
basal epithelial markers. Triple-negative breast cancers are the most common sub-
type arising in patients harboring germline mutations in the breast cancer predispo-
sition gene breast cancer 1, early onset (BRCA1). Both BRCA1-associated and the
more common sporadic triple-negative tumors share similar gene expression pro-
fi les and both are refractory to commonly used chemotherapeutic agents and as a
result are associated with a relatively poor prognosis. The p53 family member p63
controls a pathway for p73-dependent cisplatin sensitivity specifi c to these “triple-
negative” tumors. A study shows that p63 is a survival factor in a subset of breast
cancers and provide a novel mechanism for cisplatin sensitivity in these triple-
negative cancers, and suggest that such cancers may share the cisplatin sensitivity
of BRCA1-associated tumors (Leong et al. 2007 ).
Targeted Therapy of Breast Cancer with AGTR1 Antagonists To identify addi-
tional opportunities for targeted therapy, a study searched for genes with marked
overexpression in subsets of tumors across a panel of breast cancer profi ling studies
comprising 3,200 microarray experiments (Rhodes et al. 2009 ). In addition to pri-
oritizing ERBB2, the researchers found AGTR1, the angiotensin II receptor type I,
to be markedly overexpressed in 10–20 % of breast cancer cases across multiple
independent patient cohorts. Validation experiments confi rmed that AGTR1 is
highly overexpressed, in several cases more than 100-fold. AGTR1 overexpression
was restricted to estrogen receptor-positive tumors and was mutually exclusive with
ERBB2 overexpression across all samples. Ectopic overexpression of AGTR1 in
primary mammary epithelial cells, combined with angiotensin II stimulation, led to
a highly invasive phenotype that was attenuated by the AGTR1 antagonist losartan.
Similarly, losartan reduced tumor growth by 30 % in AGTR1-positive breast cancer
xenografts. Taken together, these observations indicate that marked AGTR1 overex-
pression defi nes a subpopulation of ER-positive, ERBB2-negative breast cancer
that may benefi t from targeted therapy with AGTR1 antagonists, such as losartan.
NQO1 Enzyme-Based Test for Response to Anthracycline Chemotherapy NQO1
enzyme was shown in a Helsinki University study to protect cells against oxidative
stress, and patients having one variant of the protein, NQO12, had worse survival
chances when they were treated with an anthracycline-based chemotherapy com-
pared with an alternative therapy. Women in the study who possessed a double copy
of the NQO12 variant in their genome had only a 17 % survival rate while those
with only a single copy or without the variant had a survival rate of 75 %. DNA
Repair Company has licensed the exclusive North American rights to a test from
Helsinki University and plans to use a variant of the NQO1 enzyme to create per-
sonalized medicine tests.
Preoperative Endocrine Prognostic Index (PEPI Score) is a predictive measure-
ment that could help many women diagnosed with early-stage breast cancer avoid
10 Personalized Therapy of Cancer