305chemotherapy after surgery by identifying them as having little risk of a relapse
(Ellis et al. 2008 ). About 83 % of patients are cured of breast cancer, but 17 % are
resistant to current treatments. The PEPI score is derived from tumor characteristics
that are present after women with stage 2 and 3 breast cancer undergo 4 months of
anti-estrogen therapy before having breast surgery. The PEPI score considers the size
of the breast tumor, whether cancer is present in nearby lymph nodes, how fast tumor
cells are multiplying, and whether tumors lose their estrogen receptors. Women with
a PEPI score of 0 have almost nil risk of cancer recurrence during the 5-year follow-
up. They could safely avoid taking chemotherapeutic agents after surgery. Women
with PEPI scores of 4 or above are at very high risk of having their cancer recur and
should be given all appropriate post-surgical treatments.
Decreased Breast Density as a Biomarker of Response to Tamoxifen Increased
breast density on mammography is the leading risk factor for breast cancer, apart
from age. The International Breast Intervention Study I (IBIS-I), a trial of tamoxifen
for ER-positive breast cancer prevention conducted at the Cancer Research UK
Centre for Epidemiology, Mathematics and Statistics in London has shown that a
reduction in breast density of at least 10 % may predict who benefi ts from the breast
cancer preventive effects of tamoxifen. Those with reduced breast density after 12
to 18 months of treatment had a 52 % reduced risk of breast cancer. By contrast,
those women who did not have a decrease in breast density had only an 8 % risk
reduction.
Measurement of Estrogen Receptor mRNA to Predict Response to
Tamoxifen Quantifi cation of mRNA has historically been done by RT-PCR.
A robust method of detection of mRNA utilizing ISH has been described that is
linear and shows high specifi city with low background. AQUA method of quantita-
tive immunofl uorescence (QIF) has been tested for measuring mRNA in situ using
ESR1 alpha gene in breast cancer to determine its predictive value compared to ER
protein (Bordeaux et al. 2012 ). mRNA for ER (ESR1) and Ubiquitin C (UbC) were
visualized using RNAscope probes and levels were quantifi ed by quantitative ISH
(qISH) on two Yale breast cancer cohorts on tissue microarrays. ESR1 levels were
compared to ER protein levels measured by QIF using the SP1 antibody. Results
showed that ESR1 mRNA is reproducibly and specifi cally measurable by qISH on
tissue collected from 1993 or later. ESR1 levels were correlated to ER protein levels
in a non-linear manner on two Yale cohorts. High levels of ESR1 were found to be
predictive of response to tamoxifen in a manner different from value of ER.
Prediction of Response to Chemotherapy by Intrinsic Subtypes A 50-gene sub-
type predictor was developed using microarray and quantitative RT-PCR to improve
on current standards for breast cancer prognosis and prediction of chemotherapy
(Parker et al. 2009 ). It incorporates the gene expression-based intrinsic subtypes
luminal A, luminal B, HER2-enriched, which are generally considered types with a
poor prognosis. Breast cancer experts also typically identify a fi fth breast cancer
type known as normal-like. The 50-gene set also recognizes the normal-like type,
but instead of being a fi fth type of breast cancer, the normal-like classifi cation is an
Personalized Management of Cancers of Various Organs