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. 2015 Mar 3;112(5):809-18.
doi: 10.1038/bjc.2015.8. Epub 2015 Feb 3.

Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase

D Di Gioia  1 , P Stieber  2 , G P Schmidt  3 , D Nagel  2 , V Heinemann  1 , A Baur-Melnyk  3
Affiliations

Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase

D Di Gioia et al. Br J Cancer. .

Abstract

Background: Follow-up care in breast cancer is still an issue of debate. Diagnostic methods are more sensitive, and more effective therapeutic options are now available. The risk of recurrence is not only influenced by tumour stage but also by the different molecular subtypes. This study was performed to evaluate the use of whole-body imaging combined with tumour marker monitoring for the early detection of asymptomatic metastatic breast cancer (MBC).

Methods: This analysis was performed as part of a follow-up study evaluating 813 patients with a median follow-up of 63 months. After primary therapy, all patients underwent tumour marker monitoring for CEA, CA 15-3 and CA 125 at 6-week intervals within an intensified diagnostic aftercare algorithm. A reproducible previously defined increase was considered as a strong indicator of MBC. From 2007 to 2010, 44 patients with tumour marker increase underwent whole-body magnetic resonance imaging and/or an FDG-PET/CT scan. Histological clarification and/or imaging follow-up were done.

Results: Metastases were detected in 65.9% (29/44) of patients, 13.6% (6/44) had secondary malignancies besides breast cancer and 20.5% (9/44) had no detectable malignancy. Limited disease was found in 24.1% (7/29) of patients. Median progression-free survival of MBC was 9.2 months and median overall survival was 41.1 months. The 3- and 5-year survival rates were 64.2% and 40.0%, respectively.

Conclusions: A reproducible tumour marker increase followed by whole-body imaging is highly effective for early detection. By consequence, patients might benefit from earlier detection and improved therapeutic options with a prolonged survival.

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Figures

Figure 1
Figure 1
Study design for an intensified aftercare algorithm for breast cancer patients using tumour marker monitoring combined with whole-body imaging. Since 2007, 44 patients met inclusion criteria. Twenty-eight patients showed tumour recurrence at initial exam, 6 had a secondary malignancy besides breast cancer and 10 patients showed no malignancies. In one patient, a liver metastasis was detected 6 months later in follow-up. In 2 patients with no evidence of disease, no follow-up could be acquired.
Figure 2
Figure 2
Biochemical course of tumour markers and findings by whole-body imaging. (A) A 47-year-old patient with history of breast cancer (1998) and axillary local recurrence in June 2007. Metastases to the bone were detected in February 2009. At time of tumour marker increase, CT scan shows multiple bone metastases. One osteolytic metastasis is shown here at the fifth thoracic vertebral body. (B) A 53-year-old patient with history of breast cancer (2003) and primary diagnosis of ovarian cancer in September 2008. Fluorodeoxyglucose positron emission tomography/CT showed an increased uptake in the right ovary region susceptive of ovarian cancer. The patient was treated by resection and chemotherapy. The ovarian cancer was pathologically confirmed. (C) A 58-year-old patient with history of breast cancer (2001) and a tumour marker increase in July 2007, but no detectable malignancy whether in WB-MRI nor in FDG-PET/CT at the time of initial examination; liver metastasis were finally detected in follow-up imaging after 6 months. Whole-body-MRI at initial tumour marker increase did not show any morphologic suspected lesion in the whole body. After 6 months (control MRI), the axial T2-w fat saturated sequence shows a new focal metastatic lesion in segment 4a. Computed tomography-guided biopsy confirmed metastasis. (D) An 81-year-old patient with history of breast cancer (January 1995) and tumour marker increase in October 2009. In whole-body imaging, no correlate could be found. But, at time of tumour marker increase, the patient changed her medication for hypertension. After a while, CEA levels decreased to the individual baseline.
Figure 3
Figure 3
Relapse-free survival curves are presented by breast cancer subtype (N=28).
Figure 4
Figure 4
Overall survival from time of first distant metastasis according to breast cancer subtype.
See this image and copyright information in PMC

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