Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer
Authors/Creators
- 1. Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia. mnedel30@tutanota.com.
- 2. Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences "Vinča", National Institute of Republic of Serbia, University of Belgrade, Mike Petrovića Alasa 12-14, 11351, Belgrade, Serbia.
- 3. Institute of Pathology, Faculty of Medicine, University of Belgrade, Doktora Subotića 1, 11000, Belgrade, Serbia
- 4. Department for Pathology and Cytology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia.
- 5. Department of Neurobiology, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000, Belgrade, Serbia
Description
Background: ATP-binding cassette (ABC) transporters are responsible for the efflux of a wide variety of anti-cancer agents and have been implicated in the chemoresistance of various solid tumors. Chemoresistance is a major cause of therapeutic failure, especially in the highly aggressive triple-negative breast cancer (TNBC) in which, unlike estrogen receptor-expressing (ER+) BC, both endocrine and targeted treatments are ineffectual. We aimed to investigate the level and frequency of expression of the three most important ABC transporter, ABCG2, ABCC1, and ABCB1, according to breast cancer subtype.
Methods: We evaluated ABCG2, ABCC1, and ABCB1 protein expressions in 124 primary breast tumors (78 samples were classified as TNBC, while 46 were classified as ER+) by immunohistochemistry and correlated it to clinicopathological characteristics and outcome.
Results: All three transporters had significantly higher expression and were more frequently expressed in TNBC compared to ER+ tumors (p < 0.0001). ABCG2 and ABCC1 had a very high level of expression in TNBC that was significantly greater compared to ABCB1 (p < 0.0001). ABCB1 expression was associated with TNBC metastatic spread (p = 0.03). In contrast, TNBC patients with high ABCG2 expression level had significantly longer disease-free interval (p = 0.03) and overall survival (p = 0.007).
Conclusion: ABCG2, ABCC1, and ABCB1 expression in breast cancer is subtype-specific and associated with triple-negative tumors. The expression of ABCB1 may be useful as a marker of metastatic spread. Moreover, unexpectedly, our results showed a beneficial effect of ABCG2 expression on TNBC clinical behavior. These findings could have implications for the implementation of future TNBC treatment strategies.
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Additional details
Related works
- Is identical to
- http://link.springer.com/journal/12282 (URL)
- Is part of
- 1340-6868 (ISSN)
- Is required by
- 33420675 (PMID)
Funding
- Ministry of Education, Science and Technological Development
- Molecular determinants for tumor marker design 173049
- Ministry of Education, Science and Technological Development
- Identification of predictive molecular markers for cancer progression, response to therapy and disease outcome 41031