315Tamoxin Therapy for ER-Positive Breast Cancer
For women with ER-positive early breast cancer, treatment with tamoxifen for 5
years substantially reduces the breast cancer mortality rate throughout the fi rst 15
years after diagnosis. In the worldwide Adjuvant Tamoxifen: Longer Against
Shorter (ATLAS) trial, women with early breast cancer who had completed 5 years
of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10
years or stop at 5 years in the control group (Davies et al. 2013 ). The results showed
that for women with ER-positive disease, continuing tamoxifen to 10 years rather
than stopping at 5 years produces a further reduction in recurrence and mortality,
particularly after 10 years. These results, taken together with results from previous
trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamox-
ifen treatment can reduce breast cancer mortality during the second decade after
diagnosis.
Triple Negative Breast Cancer
Subtypes of breast cancer are generally diagnosed based upon the presence or lack
of three receptors that are known to fuel most breast cancers: progesterone receptors
(PR), estrogen receptor (ER), and HER2. The most successful treatments for breast
cancer target these receptors. Unfortunately, none of these receptors are found in
women with triple negative breast cancer (TNBC), i.e. the offending tumor is
ER-negative, PR-negative and HER2-negative. Therefore, TNBCs generally do not
respond to receptor targeted treatments. However, this type of breast cancer is typi-
cally responsive to chemotherapy. Depending on the stage of its diagnosis, TNBC
can be particularly aggressive, and more likely to recur than other subtypes of breast
cancer. Metastatic TNBC (mTNBC) has a poor prognosis with median survival of
1 year as 30 % of patients suffer a recurrence after fi rst line treatment. Causative
BRCA1 mutations were detected in 9 % of TNBC patients, including patients with-
out signifi cant family histories and/or diagnosed at a later age (Rummel et al. 2013 ).
The mutation frequency in patients <60 years was 11.2–18.3 % in those patients
with signifi cant risk factors and 4.6 % in those without, while in patients >60 years,
the mutation frequency was 3.5–7.7 % in patients with risk factors, 2.3 % in those
without. Thus, evaluation of additional risk factors in both patients younger and
older than 60 years should improve the identifi cation of TNBC patients benefi ting
from genetic testing of BRCA1.
Whole genome sequencing (WGS) has revealed previously unreported muta-
tions in metastatic TNBC. Somatic genomic alterations in these advanced tumors,
particularly those that might guide targeted therapies, have been cataloged follow-
ing initial analyses of WGS and transcriptome sequencing data from prospective
metastatic mTNBC (Craig et al. 2012 ). In a sample of 14 tumors from ethnically
diverse metastatic TNBC patients, the researchers found signifi cant mutations and
other changes in more than a dozen genes through WGS performed on Life
Technologies’ SOLiD™ 4.0. The most frequently mutated gene among the tumors
Personalized Management of Cancers of Various Organs