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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 In this context, a model to predict the rate of local recurrence
conservation treatment with radiation achieves equivalent breast can- after breast conservation treatment with radiation for the individual
cer mortality and overall survival compared with mastectomy. Pro- patient could prove valuable as a source of information in the clinical
spective randomized clinical trials have demonstrated no difference in setting. In the current issue of Journal of Clinical Oncology, such a
survival for these two local treatment approaches, with 20-year out- model, IBTR! (ipsilateral breast tumor recurrence), is evaluated by
comes reported in some studies.1-4 Nonetheless, the rate of mastec- Sanghani et al.13 The IBTR! model uses clinical and pathologic factors
tomy among breast cancer patients is increasing.5-7 to predict the 10-year rate of local recurrence after breast conservation
Breast conservation treatment with radiation has been rigorously treatment with radiation.13,14
studied and validated in randomized clinical trials. The Early Breast The good news for patients is that the rate of local recurrence after
Cancer Trialists Collaborative Group meta-analysis and overview of breast conservation treatment with radiation has been declining and is
randomized trials of locoregional treatment included 10 reported relatively low in contemporary practice.13,15-20 For recently treated
clinical trials with more than 7,000 women, in which patients were patients, most studies estimate that the rate of local recurrence is
randomly assigned after breast-conserving surgery (lumpectomy with approximately 5% at 10 years (approximately 0.5% per year after
or without axillary lymph node staging) to receive radiation treatment treatment). For such recently treated patients, low rates of local recur-
versus not, and eight reported clinical trials with more than 4,000 rence have been documented in retrospective institutional studies as
women, in which patients were randomly assigned to mastectomy well as in randomized cooperative group studies, including studies by
versus breast-conserving surgery plus radiation treatment.1 There was the National Surgical Adjuvant Breast and Bowel Project. Although
no difference in breast cancer mortality or overall survival for patients the global rate of local recurrence after breast conservation treatment
randomly assigned to mastectomy compared with breast-conserving is low, individual patients may be at greater or lesser risk for local
surgery plus radiation treatment. The addition of radiation treat- recurrence depending on individual risk factors. IBTR! may be useful
ment after breast-conserving surgery was associated with a 21.7% in this regard to estimate the 10-year risk of local recurrence for
reduction in 10-year local recurrence (32.0% without radiation v individual patients and to reassure the individual patient about her
10.3% with radiation), a 5.4% reduction in 15-year breast cancer specific low risk of local recurrence. Decision aids have been shown to
mortality (35.9% v 30.5%, respectively; P .0002), and a 5.3% reduc- improve the ability of physicians to counsel and educate patients and
tion in 15-year overall mortality (40.5% v 35.2%, respectively; to alleviate anxiety.21,22
P .005). Thus, on the basis of randomized clinical trials with long- The use of patient, tumor, and treatment factors for predicting
term outcomes, the standard for breast conservation treatment in local recurrence has a long history and a large literature. Numerous
contemporary practice includes breast-conserving surgery plus defin- factors have been suggested but are not consistent from study to study.
itive radiation treatment (including radiation to the whole breast). The IBTR! model uses seven factors to predict the 10-year rate of local
Despite rigorous scientific validation and level I evidence sup- failure; these are patient age, tumor size, tumor grade, margin status,
porting breast conservation treatment with radiation, recent data in- lymphovascular invasion, use of chemotherapy, and use of hormonal
dicate that the rate of mastectomy is increasing.5-7 Although the therapy.13,14 These factors are reasonable choices for modeling local
reasons for this increase in the rate of mastectomy are unclear, possible recurrence risk.
reasons include a greater awareness of patients at high risk (for exam- One of the problems in developing a model such as IBTR! is that
ple, a known or suspected mutation in BRCA1 or BRCA2), the grow- the literature supporting various individual factors is largely retro-
ing utilization of breast magnetic resonance imaging (MRI), and the spective in nature, and individual variables often cannot be controlled
lack of adequate patient counseling and education about the increas- in randomized clinical trials. For example, patient age is one of the
ingly complex menu of local treatment options. The use of breast MRI strongest factors correlated with local failure, but patient age, of
has been associated with an increase in ipsilateral mastectomy course, cannot be controlled in retrospective or prospective research
rates.6-10 For patients with breast cancer, the use of contralateral pro- studies. Although patient age is one of the strongest and most repro-
phylactic mastectomy, including bilateral mastectomy, is also increas- ducible factors, it is possible that age represents a surrogate for unde-
ing and has been associated with the use of breast MRI.11,12 fined biologic factors.

Journal of Clinical Oncology, Vol 28, No 5 (February 10), 2010: pp 709-717 2010 by American Society of Clinical Oncology 709

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The final margin (also called final margins) of resection is one of recurrence of 8% for the patients with a triple-negative breast
the more interesting factors because it is one of the few factors that can carcinoma compared with 4% for the patients without a triple-
be controlled, at least to some extent, by physicians with the use of a negative breast carcinoma (P .041). Other biologic parameters
wider surgical excision or a re-excision. However, the term negative that have been studied relative to local recurrence include breast
margins refers to the minimum negative margin width on pathologic cancer subtype, HER2, COX-2, Bcl-2, CK19, wound-response sig-
evaluation of the lumpectomy specimen, the definition of which varies nature, and gene expression profile.30-37
from study to study. Different physicians variously define negative IBTR! has some similarities to Adjuvant!, which is a Web-based
margins as a minimum negative margin width of 1, 2, or even 5 tool that uses clinical and pathologic features to predict 10-year
mm. The National Surgical Adjuvant Breast and Bowel Project survival outcomes and response to adjuvant systemic therapy for
definition of negative margins is no tumor cells on ink from the individual patients.38-40 Adjuvant! has gained widespread accep-
lumpectomy specimen. In the setting of definitive radiation treat- tance in the medical oncology community for decision making for
ment, the goal of lumpectomy is to debulk the primary tumor adjuvant systemic therapy and for counseling and educating indi-
burden to the point where radiation can control microscopic re- vidual patients.
sidual disease in the breast, not to excise surgically every last tumor The long-term success and acceptance of Adjuvant! by the
cell from the breast. medical oncology community is attributable to its ongoing updates
Adding either adjuvant systemic chemotherapy or adjuvant hor- and inclusion of newer factors, including systemic chemotherapy
monal therapy has been correlated with improved local control in data regimens, hormonal therapy regimens, targeted therapies, and bi-
obtained from prospective randomized trials. However, the primary ologic parameters (for example, the 21-gene recurrence score as-
end points for such randomized trials typically did not include local say). Similarly, the long-term value and acceptance of IBTR! will
control, but rather more appropriate end points for the study of depend on updating the model to keep pace with future develop-
systemic therapy, such as overall survival or freedom from distant ments as new factors are found to be associated with local recur-
metastases. Thus, the true value of systemic therapy to decrease local rence. If maintained and updated on a regular basis, such a
recurrence is difficult to quantify based on secondary analyses from predictive model for local recurrence will be valuable to help individ-
such studies. ual patients understand the low risk of local recurrence in contem-
One factor not included in the IBTR! model is the use of a porary practice after breast conservation treatment with radiation
radiation boost after whole-breast radiation. In two prospective and to provide a tool for physicians to facilitate joint decision
randomized trials, the addition of a radiation boost to the primary making with patients through discussion, education, and individ-
tumor site after whole-breast radiation reduced the risk of local ualized counseling.
recurrence compared with no boost.23,24 In the European Organisa-
tion for Research and Treatment of Cancer randomized trial, patients AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
were randomly assigned to receive whole-breast irradiation of 50 The author(s) indicated no potential conflicts of interest.
Gy plus a boost dose of 16 Gy versus no boost.23 According to proto-
col specifications, a microscopically complete excision (negative
1. Clarke M, Collins R, Darby S, et al: Effects of radiotherapy and of
margins of resection) was required. For the 5,318 patients ran- differences in the extent of surgery for early breast cancer on local recurrence
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was reduced from 10.2% without a boost to 6.2% with a boost
ized trial comparing total mastectomy, lumpectomy, and lumpectomy plus
(P .0001), with a hazard ratio of 0.59 in favor of a boost. The benefit irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233-
of a boost in reducing local recurrence was maintained through 16 1241, 2002
years of follow-up after treatment. Similar improvement in local re- 3. Veronesi U, Cascinelli N, Mariani L, et al: Twenty-year follow-up of a
randomized study comparing breast-conserving surgery with radical mastectomy
currence with a boost after whole-breast radiation was seen in a second for early breast cancer. N Engl J Med 347:1227-1232, 2002
randomized clinical trial.24 4. Schwartz GF, Veronesi U, Clough KB, et al: Proceedings of the Consensus
More recent studies have evaluated the emerging role of bio- Conference on Breast Conservation, April 28 to May 1, 2005, Milan, Italy. Cancer
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5. McGuire KP, Santillan A, Kaur P, et al: Are mastectomies on the rise? A
tion treatment with radiation. Mamounas et al25 reported the value 13-year trend analysis of the selection of mastectomy versus breast conservation
of the 21-gene recurrence score assay for predicting locoregional therapy in 5865 patients. Ann Surg Oncol 16:2669-2672, 2009
recurrence. For the 390 patients treated with lumpectomy, radia- 6. Katipamula R, Degnim AC, Hoskin T, et al: Trends in mastectomy rates at
tion treatment, and adjuvant tamoxifen, the 21-gene recurrence the Mayo Clinic Rochester: Effect of surgical year and preoperative magnetic
resonance imaging. J Clin Oncol 27:4082-4088, 2009
score assay showed an interaction with patient age when correlated 7. Morrow M, Harris JR: More mastectomies: Is this what patients really
with the 10-year rate of locoregional recurrence. For patients age want? J Clin Oncol 27:4038-4040, 2009
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pretreatment magnetic resonance imaging with time to surgery, mastectomy
12.5% for a low recurrence score but significantly higher for an
rate, and margin status. J Am Coll Surg 209:180-187, 2009
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10. Houssami N, Ciatto S, Macaskill P, et al: Accuracy and surgical impact of
regardless of the recurrence score. The triple-negative subset has
magnetic resonance imaging in breast cancer staging: Systematic review and
been associated with an increased risk of local recurrence in some, meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol
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710 2010 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

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11. Tuttle TM, Habermann EB, Grund EH, et al: Increasing use of contralateral estrogen receptorpositive breast cancer: Results from NSABP B-14 and NSABP
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recurrence score assay and risk of locoregional recurrence in node-negative, on January 4, 2010

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 facilitate the provision of information to patients. A recent update of a
often want a great deal of information. Many oncologists would agree Cochrane review of patient decision aids in oncology, for exam-
that appropriately informing the patient is a central tenet of quality ple, identified 23 randomized trials of decision aids in a variety of
medical care. Evidence in the literature shows that the provision of cancer settings and concluded that, across studies, persons randomly
relevant information to patients can be associated with improved assigned to decision aids were more likely to participate in decision
satisfaction with care, decreased patient anxiety, improved recovery making and to achieve higher quality decisions.2 The effectiveness of
from treatment, improved compliance, and improved ability to par- decision aids and other educational materials depends not only on the
ticipate in health care decisions.1 Accordingly, educational tools, treat- accurate representation of clinically relevant outcomes, but also on pre-
ment decision aids, and other interventions have been designed to sentation of the data in a way that patients can understand the outcomes. 2010 by American Society of Clinical Oncology 711

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