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CLINICAL INVESTIGATION Breast
PROGNOSTIC INDEX SCORE AND CLINICAL PREDICTION MODEL OF
LOCAL REGIONAL RECURRENCE AFTER MASTECTOMY IN BREAST
CANCER PATIENTS
SKYE HONGIUN CHENG, M.D.,*
#
CHENG-FANG HORNG, M.S.,
**
AND LEONARD R. PROSNITZ, M.D.
#
Departments of *Radiation Oncology,
Research,
Pathology,
Medical Oncology, and
Surgical Oncology, Koo Foundation Sun
Yat-Sen Cancer Center, Taipei, Taiwan;
Institute of Statistics and Decision Sciences and Departments of
#
Radiation Oncology,
**Medicine, and
Biostatistics and Bioinformatics, Duke University, Durham, North Carolina
Purpose: To develop clinical prediction models for local regional recurrence (LRR) of breast carcinoma after
mastectomy that will be superior to the conventional measures of tumor size and nodal status.
Methods and Materials: Clinical information from 1,010 invasive breast cancer patients who had primary
modied radical mastectomy formed the database of the training and testing of clinical prognostic and prediction
models of LRR. Cox proportional hazards analysis and Bayesian tree analysis were the core methodologies from
which these models were built. To generate a prognostic index model, 15 clinical variables were examined for
their impact on LRR. Patients were stratied by lymph node involvement (<4 vs. >4) and local regional status
(recurrent vs. control) and then, within strata, randomly split into training and test data sets of equal size. To
establish prediction tree models, 255 patients were selected by the criteria of having had LRR (53 patients) or no
evidence of LRR without postmastectomy radiotherapy (PMRT) (202 patients).
Results: With these models, patients can be divided into low-, intermediate-, and high-risk groups on the basis
of axillary nodal status, estrogen receptor status, lymphovascular invasion, and age at diagnosis. In the low-risk
group, there is no inuence of PMRT on either LRR or survival. For intermediate-risk patients, PMRT improves
LR control but not metastases-free or overall survival. For the high-risk patients, however, PMRT improves both
LR control and metastasis-free and overall survival.
Conclusion: The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast
cancer patients after mastectomy and for estimating the potential benets of PMRT. These models provide
additional information criteria for selection of patients for PMRT, compared with the traditional selection
criteria of nodal status and tumor size. 2006 Elsevier Inc.
Breast cancer, Mastectomy, Radiotherapy, Prediction model, Prognostic score.
INTRODUCTION
Postmastectomy radiotherapy (PMRT) clearly reduces the
frequency of local regional recurrence (LRR) in high-risk
breast cancer patients (1). It also seems to impact favorably
on survival (2). The delineation of patients at high risk for
LRR is controversial, however. Conventionally, the number
of involved axillary lymph nodes and the size of the primary
tumor are considered, and PMRT is generally recommended
for those with 4 or more involved axillary lymph nodes
and/or those with large primary tumors (T3 or greater)
(35). However, three randomized trials in which a survival
benet for PMRT was demonstrated included primarily
NoteAn online CME test for this article can be taken at
www.astro.org under Education and Meetings.
Reprint requests to: Skye H. Cheng, M.D., Koo Foundation Sun
Yat-Sen Cancer Center, Department of Radiation Oncology, No.
125, Lih-Der Road, Pei-Tou District, Taipei, Taiwan. Tel: (886)
2-28970011, ext. 310; Fax: (886) 2-28972233; E-mail: skye@
mail.kfcc.org.tw
Supported in part by research funds from Koo Foundation Sun
Yat-Sen Cancer Center and in part by a grant from the National
Health Research Institutes of Taiwan (Contract Project 1997, No.
DD01-86IX-CR601S).
AcknowledgmentsThe authors thank the members of the Breast
Cancer Team at Koo Foundation Sun Yat-Sen Cancer Center: Drs.
Po-Sheng Yang and Ben-Long Yu (Department of Surgery), Drs.
H.H. Lin and M.Y. Lee (Department of Pathology), Drs. Kwan-
Yee Chan and Christopher K.J. Lin (Department of Radiology),
Drs. Tran-Der Tan, Cheng-I Hsieh, and Nei-Min Chu (Department
of Medical Oncology), and Dr. Yu-Ling Chung (Department of
Radiation Oncology) for patient care; and Yen-Chun Lin, Yueh-
Yun Yu, Yi-Wen Chang, and An-Chen Feng in the Clinical Pro-
tocol Ofce for data collection, data entry, data quality control, and
outcome analysis.
Received April 2, 2005, and in revised form Nov 15, 2005.
Accepted for publication Nov 15, 2005.
Int. J. Radiation Oncology Biol. Phys., Vol. 64, No. 5, pp. 14011409, 2006
Copyright 2006 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/06/$see front matter
1401
patients with 13 positive lymph nodes (68). Thus, a
better denition of what constitutes a patient at high risk for
LRR and who would be expected to benet from PMRT
would be valuable.
Several other prognostic factors, such as estrogen recep-
tor (ER) status, age, lymphovascular invasion (LVI), and
extracapsular extension of tumor in axillary lymph nodes
have previously been identied as predictive for LRR after
mastectomy (911). The interaction between these factors,
however, is largely unknown.
The aim of this study was to develop more sophisticated
prediction models for LRR after mastectomy, by using
readily available clinical data in a fashion analogous to the
development of the International Prognostic Index for pa-
tients with non-Hodgkins lymphomas (12). To accomplish
this, both traditional Cox proportional hazards models and
Bayesian classication trees were used to estimate the prob-
ability of LRR after mastectomy for individual breast cancer
patients (1315).
METHODS AND MATERIALS
Treatment policies
Between April 1999 and December 2001, 1,143 patients under-
went modied radical mastectomy as initial treatment for newly
diagnosed invasive breast cancer at the Koo Foundation, Sun
Yat-Sen Cancer Center in Taipei, Taiwan. Adjuvant treatment
policies were as follows.
Postmastectomy radiotherapy. Before 1997, patients received
PMRT if they had involvement of 4 or more axillary lymph nodes
or a primary tumor 5 cm in size or a resection margin positive or
close. After 1997, patients with 13 axillary lymph nodes involved
were also candidates for PMRT if combined with another risk
factor, specically a primary tumor 3 cm, ER-negative status,
age 40 years, or the presence of LVI.
The technique for PMRT included radiation elds specically
directed to the ipsilateral chest wall and internal mammary chain
and supraclavicular lymph nodes with CT-based treatment plan-
ning. The heart was largely excluded from the radiation elds. The
central lung distance of the tangents elds was limited to a max-
imum of 3 cm. Internal mammary chain nodes were either included
in wide tangent elds if the included lung was acceptable or treated
with a separate photon/electron eld. The full axilla was excluded
from the radiation elds. The dose of radiation was 4550 Gy in 25
fractions (16).
Adjuvant systemic therapy. Before 2000, node-positive patients
were treated with one of four chemotherapy regimensAC (doxoru-
Table 1. Clinical characteristics of patients in the training and
test data sets
Characteristic
Training Test
P value* (n 506) (n 504)
Age (y)
35 44 44 0.88
3640 72 74
4150 194 181
50 196 205
Menstruation status
Premenopausal 312 299 0.45
Postmenopausal 194 205
Family history
No 451 453 0.87
1st or 2nd degree 52 49
Others 3 2
Histology
Favorable
26 24 0.36
Inltrating ductal 430 416
Other invasive 50 64
Pathological tumor size
(cm)
2.0 230 227 0.89
2.0 276 277
No. of axillary nodes
dissected
10 24 15 0.32
1019 226 211
2029 192 209
30 64 69
No. of axillary nodes
positive
0 248 250 0.76
13 144 142
49 70 61
9 44 51
Extracapsular extension
Negative 378 366 0.58
Positive 121 133
Unknown 7 5
Estrogen receptor status
Negative 137 154 0.29
102 111
137 110
130 129
Lymphovascular invasion
Absent 266 268 0.35
Focal 85 100
Prominent 155 139
Nuclear grade
1 93 77 0.37
2 158 168
3 249 259
Surgical margins
Negative 493 483 0.43
Close (2 mm) 7 14
Positive 1 2
Unknown 5 5
Adjuvant radiotherapy
Yes 137 123 0.33
No 369 381
Adjuvant hormonal therapy
Yes 363 362 0.98
No 143 142
(Continued)
Table 1. Clinical characteristics of patients in the training and
test data sets (Continued)
Characteristic
Training Test
P value* (n 506) (n 504)
Adjuvant chemotherapy
Yes 369 362 0.70
No 137 142
* Chi-square test.