Development and verification of a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer.
OBJECTIVE
The aim of this study was to develop a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer.


METHODS
We retrospectively analyzed a training set of 105 patients with metastatic or recurrent breast cancer. Their chemotherapeutic response had been evaluated according to the World Health Organization (WHO)'s response criteria. Our model for predicting response using carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, and NCC-ST-439 was determined using the area under the receiver operating characteristic curve (ROC-AUC) and the overall misclassification rate (OMR) in a random cross-validation. The prediction model was then verified in a consecutive set of 64 patients. Their response had been evaluated using the response evaluation criteria in solid tumors (RECIST) criteria.


RESULTS
The best prediction model consisted of the serum CEA, CA15-3, and NCC-ST-439 levels, but the prediction formula varied according to the baseline CA15-3 level (elevated or normal). The overall ROC-AUC and OMR in the training set were 0.83 and 0.19, respectively. The overall ROC-AUC and OMR in the verification set were 0.72 and 0.28, respectively. When the verification set was stratified according to either the objective response or the predicted response, the time-to-progression, but not the overall survival, was significantly different.


CONCLUSIONS
Our model for predicting the response to first-line chemotherapy of patients with metastatic or recurrent breast cancer may be valid because it predicted the outcome of more than 70% of the patients in an independent verification set.
Yonemori
Kan
K
Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. kyonemor@ncc.go.jp
Katsumata
Noriyuki
N
Noda
Ayako
A
Uno
Hajime
H
Yunokawa
Mayu
M
Nakano
Eriko
E
Kouno
Tsutomu
T
Shimizu
Chikako
C
Ando
Masashi
M
Tamura
Kenji
K
Takeuchi
Masahiro
M
Fujiwara
Yasuhiro
Y
D000328:Adult; D000368:Aged; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D011237:Predictive Value of Tests; D017697:Premenopause
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; C056315:ST 439 antigen, human