VOLUME 28 NUMBER 5 FEBRUARY 10 2010
JOURNAL OF CLINICAL ONCOLOGY
Breast Conservation Treatment With Radiation: An
Ongoing Success Story
Lawrence J. Solin, Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia, PA
See accompanying article on page 718
For women with early-stage invasive breast carcinoma, breast
conservation treatment with radiation achieves equivalent breast can-
cer mortality and overall survival compared with mastectomy. Pro-
spective randomized clinical trials have demonstrated no difference in
survival for these two local treatment approaches, with 20-year out-
comes reported in some studies.1-4 Nonetheless, the rate of mastec-
tomy among breast cancer patients is increasing.5-7
Breast conservation treatment with radiation has been rigorously
studied and validated in randomized clinical trials. The Early Breast
Cancer Trialists Collaborative Group meta-analysis and overview of
randomized trials of locoregional treatment included 10 reported
clinical trials with more than 7,000 women, in which patients were
randomly assigned after breast-conserving surgery (lumpectomy with
or without axillary lymph node staging) to receive radiation treatment
versus not, and eight reported clinical trials with more than 4,000
women, in which patients were randomly assigned to mastectomy
versus breast-conserving surgery plus radiation treatment.1 There was
no difference in breast cancer mortality or overall survival for patients
randomly assigned to mastectomy compared with breast-conserving
surgery plus radiation treatment. The addition of radiation treat-
ment after breast-conserving surgery was associated with a 21.7%
reduction in 10-year local recurrence (32.0% without radiation v
10.3% with radiation), a 5.4% reduction in 15-year breast cancer
mortality (35.9% v 30.5%, respectively; P .0002), and a 5.3% reduc-
tion in 15-year overall mortality (40.5% v 35.2%, respectively;
P .005). Thus, on the basis of randomized clinical trials with long-
term outcomes, the standard for breast conservation treatment in
contemporary practice includes breast-conserving surgery plus defin-
itive radiation treatment (including radiation to the whole breast).
Despite rigorous scientific validation and level I evidence sup-
porting breast conservation treatment with radiation, recent data in-
dicate that the rate of mastectomy is increasing.5-7 Although the
reasons for this increase in the rate of mastectomy are unclear, possible
reasons include a greater awareness of patients at high risk (for exam-
ple, a known or suspected mutation in BRCA1 or BRCA2), the grow-
ing utilization of breast magnetic resonance imaging (MRI), and the
lack of adequate patient counseling and education about the increas-
ingly complex menu of local treatment options. The use of breast MRI
has been associated with an increase in ipsilateral mastectomy
rates.6-10 For patients with breast cancer, the use of contralateral pro-
phylactic mastectomy, including bilateral mastectomy, is also increas-
ing and has been associated with the use of breast MRI.11,12
Journal of Clinical Oncology, Vol 28, No 5 (February 10), 2010: pp 709-717
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E D I T O R I A L
In this context, a model to predict the rate of local recurrence
after breast conservation treatment with radiation for the individual
patient could prove valuable as a source of information in the clinical
setting. In the current issue of Journal of Clinical Oncology, such a
model, IBTR! (ipsilateral breast tumor recurrence), is evaluated by
Sanghani et al.13 The IBTR! model uses clinical and pathologic factors
to predict the 10-year rate of local recurrence after breast conservation
treatment with radiation.13,14
The good news for patients is that the rate of local recurrence after
breast conservation treatment with radiation has been declining and is
relatively low in contemporary practice.13,15-20 For recently treated
patients, most studies estimate that the rate of local recurrence is
approximately 5% at 10 years (approximately 0.5% per year after
treatment). For such recently treated patients, low rates of local recur-
rence have been documented in retrospective institutional studies as
well as in randomized cooperative group studies, including studies by
the National Surgical Adjuvant Breast and Bowel Project. Although
the global rate of local recurrence after breast conservation treatment
is low, individual patients may be at greater or lesser risk for local
recurrence depending on individual risk factors. IBTR! may be useful
in this regard to estimate the 10-year risk of local recurrence for
individual patients and to reassure the individual patient about her
specific low risk of local recurrence. Decision aids have been shown to
improve the ability of physicians to counsel and educate patients and
to alleviate anxiety.21,22
The use of patient, tumor, and treatment factors for predicting
local recurrence has a long history and a large literature. Numerous
factors have been suggested but are not consistent from study to study.
The IBTR! model uses seven factors to predict the 10-year rate of local
failure; these are patient age, tumor size, tumor grade, margin status,
lymphovascular invasion, use of chemotherapy, and use of hormonal
therapy.13,14 These factors are reasonable choices for modeling local
recurrence risk.
One of the problems in developing a model such as IBTR! is that
the literature supporting various individual factors is largely retro-
spective in nature, and individual variables often cannot be controlled
in randomized clinical trials. For example, patient age is one of the
strongest factors correlated with local failure, but patient age, of
course, cannot be controlled in retrospective or prospective research
studies. Although patient age is one of the strongest and most repro-
ducible factors, it is possible that age represents a surrogate for unde-
fined biologic factors.
2010 by American Society of Clinical Oncology 709
 Editorials
The final margin (also called final margins) of resection is one of
the more interesting factors because it is one of the few factors that can
be controlled, at least to some extent, by physicians with the use of a
wider surgical excision or a re-excision. However, the term negative
margins refers to the minimum negative margin width on pathologic
evaluation of the lumpectomy specimen, the definition of which varies
from study to study. Different physicians variously define negative
margins as a minimum negative margin width of 1, 2, or even 5
mm. The National Surgical Adjuvant Breast and Bowel Project
definition of negative margins is no tumor cells on ink from the
lumpectomy specimen. In the setting of definitive radiation treat-
ment, the goal of lumpectomy is to debulk the primary tumor
burden to the point where radiation can control microscopic re-
sidual disease in the breast, not to excise surgically every last tumor
cell from the breast.
Adding either adjuvant systemic chemotherapy or adjuvant hor-
monal therapy has been correlated with improved local control in data
obtained from prospective randomized trials. However, the primary
end points for such randomized trials typically did not include local
control, but rather more appropriate end points for the study of
systemic therapy, such as overall survival or freedom from distant
metastases. Thus, the true value of systemic therapy to decrease local
recurrence is difficult to quantify based on secondary analyses from
such studies.
One factor not included in the IBTR! model is the use of a
radiation boost after whole-breast radiation. In two prospective
randomized trials, the addition of a radiation boost to the primary
tumor site after whole-breast radiation reduced the risk of local
recurrence compared with no boost.23,24 In the European Organisa-
tion for Research and Treatment of Cancer randomized trial, patients
were randomly assigned to receive whole-breast irradiation of 50
Gy plus a boost dose of 16 Gy versus no boost.23 According to proto-
col specifications, a microscopically complete excision (negative
margins of resection) was required. For the 5,318 patients ran-
domly assigned in the European Organisation for Research and
Treatment of Cancer study, the 10-year rate of local recurrence
was reduced from 10.2% without a boost to 6.2% with a boost
(P .0001), with a hazard ratio of 0.59 in favor of a boost. The benefit
of a boost in reducing local recurrence was maintained through 16
years of follow-up after treatment. Similar improvement in local re-
currence with a boost after whole-breast radiation was seen in a second
randomized clinical trial.24
More recent studies have evaluated the emerging role of bio-
logic factors associated with local recurrence after breast conserva-
tion treatment with radiation. Mamounas et al25 reported the value
of the 21-gene recurrence score assay for predicting locoregional
recurrence. For the 390 patients treated with lumpectomy, radia-
tion treatment, and adjuvant tamoxifen, the 21-gene recurrence
score assay showed an interaction with patient age when correlated
with the 10-year rate of locoregional recurrence. For patients age
less than 50 years, the 10-year rate of locoregional recurrence was
12.5% for a low recurrence score but significantly higher for an
intermediate or high recurrence score (27.7% and 26.5%, respec-
tively). In contrast, for patients age 50 years, all patients had a
low risk of locoregional recurrence (between 3.6% and 4.8%)
regardless of the recurrence score. The triple-negative subset has
been associated with an increased risk of local recurrence in some,
but not all, studies.26-30 Solin et al26 reported an 8-year rate of local
710 2010 by American Society of Clinical Oncology
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Copyright 2016 American Society of Clinical Oncology. All rights reserved.
recurrence of 8% for the patients with a triple-negative breast
carcinoma compared with 4% for the patients without a triple-
negative breast carcinoma (P .041). Other biologic parameters
that have been studied relative to local recurrence include breast
cancer subtype, HER2, COX-2, Bcl-2, CK19, wound-response sig-
nature, and gene expression profile.30-37
IBTR! has some similarities to Adjuvant!, which is a Web-based
tool that uses clinical and pathologic features to predict 10-year
survival outcomes and response to adjuvant systemic therapy for
individual patients.38-40 Adjuvant! has gained widespread accep-
tance in the medical oncology community for decision making for
adjuvant systemic therapy and for counseling and educating indi-
vidual patients.
The long-term success and acceptance of Adjuvant! by the
medical oncology community is attributable to its ongoing updates
and inclusion of newer factors, including systemic chemotherapy
regimens, hormonal therapy regimens, targeted therapies, and bi-
ologic parameters (for example, the 21-gene recurrence score as-
say). Similarly, the long-term value and acceptance of IBTR! will
depend on updating the model to keep pace with future develop-
ments as new factors are found to be associated with local recur-
rence. If maintained and updated on a regular basis, such a
predictive model for local recurrence will be valuable to help individ-
ual patients understand the low risk of local recurrence in contem-
porary practice after breast conservation treatment with radiation
and to provide a tool for physicians to facilitate joint decision
making with patients through discussion, education, and individ-
ualized counseling.
AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
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Is Seeing Believing?
Michael D. Brundage, Division of Cancer Care and Epidemiology, Queens University Cancer Research Institute, Kingston,
Ontario, Canada
See accompanying article on page 738
The literature is replete with evidence that patients with cancer
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relevant information to patients can be associated with improved
satisfaction with care, decreased patient anxiety, improved recovery
from treatment, improved compliance, and improved ability to par-
ticipate in health care decisions.1 Accordingly, educational tools, treat-
ment decision aids, and other interventions have been designed to
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estrogen receptorpositive breast cancer: Results from NSABP B-14 and NSABP
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DOI: 10.1200/JCO.2009.26.1164; published online ahead of print at
www.jco.org on January 4, 2010
facilitate the provision of information to patients. A recent update of a
Cochrane review of patient decision aids in oncology, for exam-
ple, identified 23 randomized trials of decision aids in a variety of
cancer settings and concluded that, across studies, persons randomly
assigned to decision aids were more likely to participate in decision
making and to achieve higher quality decisions.2 The effectiveness of
decision aids and other educational materials depends not only on the
accurate representation of clinically relevant outcomes, but also on pre-
sentation of the data in a way that patients can understand the outcomes.
2010 by American Society of Clinical Oncology 711