choice of treatment is based mainly on HR
status (ie, the ER and/or PR) and HER2
is the mainstay of adjuvant chemotherapy,
regardless of nodal status.
and the anti-HER2 trastuzumab should be
offered, regardless of the nodal or HR status. HER2-positive disease is defined as a
finding of HER2 protein 3+ by immunohisto-chemistry (circumferential membrane staining that is complete, intense, and in >10%
of tumor cells) or as the presence of HER2
gene amplification by FISH defined as either
( 1) dual probe HER2/CEP17 ratio ≥ 2.0 with
an average HER2 copy number ≥4.0 signals
per cell; ( 2) dual probe HER2/CEP17 ratio
of ≥ 2.0 with an average HER2 copy number <4.0 signals/cell; ( 3) dual probe HER2/
CEP17 ratio < 2.0 with an average HER2
copy number > 6.0 signals/cell; or (4) single-probe average HER2 copy number ≥ 6 signals/cell.22 In ER-positive and/or PR-positive
breast cancer, endocrine (hormonal) therapy
should be used as adjuvant therapy for
almost all women, regardless of nodal or
HER2 status. Hormonal therapy is generally
given after completion of chemotherapy, if
chemotherapy is indicated.
HER2-negative breast cancer that is node
negative (N0), additional tests are recommended to determine the benefit of chemotherapy. The most widely used genomic
test in the United States is the 21-gene RS
assay, the Oncotype DX,20 as noted above.
ER-positive tumors. This assay helps predict
the benefit from adding chemotherapy to
hormonal therapy compared with hormonal
therapy alone. The subset of patients with a
high RS (defined as ≥31) benefit from chemotherapy.
negative breast cancer that is node-negative,
clinical judgment should always be exercised
in assessing the benefit from adding chemotherapy to endocrine therapy, and additional
factors should be considered in the decision
making regarding chemotherapy, such as
high histologic grade and young age (
younger than 50 years).
ER-positive and/or PR-positive, HER2-nega-
tive, and node-positive disease is less certain
and is being tested in a large randomized trial
with node-positive disease who have an RS
of 25 or lower to chemotherapy plus endocrine therapy or endocrine therapy alone.
CURRENT CHEMOTHERAPY OPTIONS
EVOLUTION OF ADJUVANT CHEMOTHERAPY
The first chemotherapy combination regimen
used on a large scale for breast cancer was the
CMF (cyclophosphamide, methotrexate, and 5-flu-
orouracil) regimen.23 Six cycles of CMF was the
gold standard of adjuvant chemotherapy in breast
cancer for decades, and it significantly improved
early and long-term results and conferred better
rates of relapse-free survival and overall survival
(OS) compared with no chemotherapy.24 Multiple
subsequent regimens were developed and contributed to improved outcome in breast cancer.