Abstract
The detection of circulating tumor cells (CTCs) in the peripheral blood of metastatic breast cancer (MBC) patients is an independent marker of prognosis. This large prospective multicenter study aimed to assess the impact of CTCs on overall survival (OS) and progression free survival (PFS) in patients with predefined molecular subgroups of MBC. To this end, 468 MBC patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HorR+/HER2−), (2) HER2-positive (HER2+), and (3) HorR-negative/HER2-negative (HorR−/HER2−) patients. CTC status (<5 CTCs/7.5 ml blood (CTC-negative) vs. ≥5 CTCs/7.5 ml blood (CTC-positive)) was determined using the CellCearch® system before patients started a new line of therapy. At baseline, 205 (42 %) patients were CTC-positive. On multivariate analysis, CTC-positivity was an independent prognostic factor for shorter PFS and OS. In HorR+/HER2− patients, median PFS [95 % CI] of CTC-negative versus CTC-positive patients was 8.60 [5.93–11.27] versus 4.33 [3.29–5.38] months (p < 0.001), in HER2+ patients 7.60 [5.40–9.79] versus 6.60 [4.20–9.00] months (p = 0.477) and in HorR−/HER2− patients 5.83 [5.09–6.78] versus 3.05 [1.81–4.29] months (p < 0.001), respectively. Median OS [95 % CI] of CTC-negative versus CTC-positive patients was as follows: not reached by either in the HorR+/HER2− subgroup (p < 0.001), not reached versus 18.07 [11.10–25.05] months (p = 0.001) in the HER2+ subgroup, and not reached versus 8.57 [4.07–13.07] months in the HorR−/HER2− subgroup (p = 0.001). In conclusion, our results strongly confirm the independent prognostic value of CTC enumeration in MBC patients. In contrast to recent reports, there was no association between primary tumor-based molecular subgroups and the impact of CTC status on OS. Hence, CTC status may help to identify patients who require aggressive therapy, especially among those with triple-negative MBC.
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Abbreviations
- CI:
-
Confidence interval
- CTC(s):
-
Circulating tumor cell(s)
- CTC−:
-
CTC-negative
- CTC+:
-
CTC-positive
- EpCam:
-
Epithelial cell adhesion molecule
- ER:
-
Estrogen receptor
- FDA:
-
Food and drug administration (USA)
- HER2:
-
Human epidermal growth factor receptor 2
- HorR:
-
Hormone receptor
- MBC:
-
Metastatic breast cancer
- OS:
-
Overall survival
- PFS:
-
Progression free survival
- PgR:
-
Progesterone receptor
- RECIST:
-
Response evaluation criteria in solid tumors
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Acknowledgments
We are grateful to the patients who participated in this study. We also wish to acknowledge the medical and nursing staff at the participating centers.
Conflict of interest
KP, BR and WJ has received funding from Veridex. The other authors declare that they have no conflict of interest.
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Markus Wallwiener, Andreas Daniel Hartkopf, Andreas Schneeweiss, and Tanja Natascha Fehm are joint authors.
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Wallwiener, M., Hartkopf, A.D., Baccelli, I. et al. The prognostic impact of circulating tumor cells in subtypes of metastatic breast cancer. Breast Cancer Res Treat 137, 503–510 (2013). https://doi.org/10.1007/s10549-012-2382-0
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DOI: https://doi.org/10.1007/s10549-012-2382-0