substudy of the National Surgical Adjuvant
Breast and Bowel Project (NSABP) B- 14 clinical trial in which patients with node-negative,
ER-positive tumors were randomly assigned
to receive tamoxifen or placebo without chemotherapy. 22 Using the standard reported
values of low risk (< 18), intermediate risk
( 18–30), or high risk (≥ 31) for recurrence,
among the tamoxifen-treated patients, cancers with a high-risk recurrence score had a
significantly worse rate of distant recurrence
and overall survival. 21 Inferior breast cancer
survival in cancers with a high recurrence
score was also confirmed in other series
of endocrine-treated patients with node-negative and node-positive disease. 23–25
The predictive utility of the 21-gene recurrence score for endocrine therapy has also
been evaluated. A comparison of the pla-cebo- and tamoxifen-treated patients from
the NSABP B- 14 trial demonstrated that the
21-gene recurrence score predicted benefit
from tamoxifen in cancers with low- or inter-mediate-risk recurrence scores. 26 However,
there was no benefit from the use of tamoxifen over placebo in cancers with high-risk
recurrence scores. To date, this intriguing
data has not been prospectively confirmed,
and thus the 21-gene recurrence score is not
used to avoid endocrine therapy.
The 21-gene recurrence score is primarily
used by oncologists to aid in decision-making
regarding adjuvant chemotherapy in patients
with node-negative and node-positive (with
up to 3 positive lymph nodes), HR-positive/
HER2-negative breast cancers. The predictive
utility of the 21-gene recurrence score for
adjuvant chemotherapy was initially tested
using tumor samples from the NSABP B- 20
study. This study initially compared adjuvant
tamoxifen alone with tamoxifen plus che-
motherapy in patients with node-negative,
HR-positive tumors. The prospective-
retrospective biomarker analysis showed that
the patients with high-risk 21-gene recur-
rence scores benefited from the addition
of chemotherapy, whereas those with low or
intermediate risk did not have an improved
freedom from distant recurrence with che-
motherapy. 27 Similarly, an analysis from the
prospective phase 3 Southwest Oncology
Group (SWOG) 8814 trial comparing
tamoxifen to tamoxifen with chemotherapy
showed that for node-positive tumors, che-
motherapy benefit was only seen in those
with high 21-gene recurrence scores. 24
Prospective studies are now starting to
report results regarding the predictive role of
the 21-gene recurrence score. The TAILORx
(Trial Assigning Individualized Options for
Treatment) trial includes women with node-negative, HR-positive/HER2-negative tumors
measuring 0.6 to 5 cm. All patients were
treated with standard-of-care endocrine therapy for at least 5 years. Chemotherapy was
determined based on the 21-gene recurrence score results on the primary tumor.
The 21-gene recurrence score cutoffs
were changed to low (0– 10), intermediate
( 11–25), and high (≥ 26). Patients with scores
of 26 or higher were treated with chemotherapy, and those with intermediate scores
were randomly assigned to chemotherapy or
no chemotherapy; results from this cohort
are still pending. However, excellent breast
cancer outcomes with endocrine therapy
alone were reported from the 1626 ( 15.9% of
total cohort) prospectively followed patients
with low recurrence score tumors. The 5-year
invasive disease-free survival was 93.8%, with
overall survival of 98%. 28 Given that 5 years
is appropriate follow-up to see any chemotherapy benefit, this data supports the recommendation for no chemotherapy in this
