Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

1.
Corso
G
,
Maisonneuve
P
,
Santomauro
GI
,
De Scalzi
AM
,
Toesca
A
,
Bassi
FD
, et al
Ipsilateral breast tumor reappearance and contralateral breast cancer after primary breast cancer treatment: a comprehensive retrospective study of 15,168 patients
.
Oncology
.
2018
;
95
(
3
):
147
55
.
2.
Chang
HT
,
Hu
C
,
Chiu
YL
,
Peng
NJ
,
Liu
RS
.
Role of 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in the post-therapy surveillance of breast cancer
.
PLoS One
.
2014
;
9
(
12
):
e115127
.
3.
Corso
G
,
Maisonneuve
P
,
Massari
G
,
Invento
A
,
Pravettoni
G
,
De Scalzi
A
, et al
Validation of a novel nomogram for prediction of local relapse after surgery for invasive breast carcinoma
.
Ann Surg Oncol
.
2020
;
27
(
6
):
1864
74
.
4.
Sacchini
V
.
Restaging patients with locoregional relapse: is there any benefit? Commentary on “Radiological staging for distant metastases in breast cancer patients with confirmed local and/or locoregional recurrence: how useful are current guideline recommendations?” by Elfgen, Constanze et al
.
Ann Surg Oncol
.
2019
;
26
(
11
):
3415
7
.
5.
Di Lascio
S
,
Pagani
O
.
Oligometastatic breast cancer: a shift from palliative to potentially curative treatment?
Breast Care (Basel)
.
2014
;
9
(
1
):
7
14
.
6.
Harris
L
,
Fritsche
H
,
Mennel
R
,
Norton
L
,
Ravdin
P
,
Taube
S
, et al
American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer
.
J Clin Oncol
.
2007
;
25
(
33
):
5287
312
.
7.
Cardoso
F
,
Saghatchian
M
,
Thompson
A
,
Rutgers
E
;
TRANSBIG Consortium Steering Committee
.
Inconsistent criteria used in American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer
.
J Clin Oncol
.
2008
;
26
(
12
):
2058
9
; author reply 2060–1
.
8.
Khatcheressian
JL
,
Hurley
P
,
Bantug
E
,
Esserman
LJ
,
Grunfeld
E
,
Halberg
F
, et al
Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update
.
J Clin Oncol
.
2013
;
31
(
7
):
961
5
.
9.
Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators
.
JAMA
.
1994
;
271
(
20
):
1587
92
.
10.
Champion
L
,
Brain
E
,
Giraudet AL
,
Le Stanc
E
,
Wartski
M
,
Edeline
V
, et al
Breast cancer recurrence diagnosis suspected on tumor marker rising: value of whole-body 18FDG-PET/CT imaging and impact on patient management
.
Cancer
.
2011
;
117
(
8
):
1621
9
.
11.
Evangelista
L
,
Cervino
AR
,
Ghiotto
C
,
Al-Nahhas
A
,
Rubello
D
,
Muzzio
PC
.
Tumor marker-guided PET in breast cancer patients – a recipe for a perfect wedding: a systematic literature review and meta-analysis
.
Clin Nucl Med
.
2012
;
37
(
5
):
467
74
.
12.
Filippi
V
,
Malamitsi
J
,
Vlachou
F
,
Laspas
F
,
Georgiou
E
,
Prassopoulos
V
, et al
The impact of FDG-PET/CT on the management of breast cancer patients with elevated tumor markers and negative or equivocal conventional imaging modalities
.
Nucl Med Commun
.
2011
;
32
(
2
):
85
90
.
13.
Piva
R
,
Ticconi
F
,
Ceriani
V
,
Scalorbi
F
,
Fiz
F
,
Capitanio
S
, et al
Comparative diagnostic accuracy of 18F-FDG PET/CT for breast cancer recurrence
.
Breast Cancer (Dove Med Press)
.
2017
;
9
:
461
71
.
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