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Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer

  • Authors:
    • Helena Fohlin
    • Tove Bekkhus
    • Josefine Sandström
    • Tommy  Fornander
    • Bo Nordenskjöld
    • John Carstensen
    • Olle Stål
  • View Affiliations / Copyright

    Affiliations: Regional Cancer Center Southeast Sweden, SE‑581 85 Linköping, Sweden, Department of Clinical and Experimental Medicine and Oncology, Linköping University, SE‑581 83 Linköping, Sweden, Department of Oncology, Karolinska University Hospital, Karolinska Institute, SE‑171 77 Stockholm, Sweden, Division of Health and Society, Department of Medical and Health Sciences, Linköping University, SE‑581 83 Linköping, Sweden
    Copyright: © Fohlin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 415-420
    |
    Published online on: March 9, 2020
       https://doi.org/10.3892/mco.2020.2014
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Abstract

Over the last few decades, improved and more individualized treatment has contributed to the increased survival rate of patients with breast cancer. However, certain patients may receive excessive treatment resulting in undesired side effects. In a previous study, it was demonstrated that systemically untreated patients with estrogen receptor (ER)‑positive/progesterone receptor (PR)‑negative tumors with high Ras‑related protein Rab‑6C (RAB6C) expression levels (RAB6C+) had prolonged distant recurrence‑free survival compared with that of patients exhibiting low RAB6C (RAB6C‑)‑expressing tumors. The aim of the present study was to investigate whether RAB6C predicts the effectiveness of tamoxifen treatment. The present study used a dataset comprising 486 female patients with ER+ tumors from a randomized study conducted by the Stockholm Breast Cancer Study Group between November 1976 and August 1990. The patients were considered as low‑risk if their tumor size was ≤30 mm and their lymph node status was negative. Patients were followed up until distant recurrence, mortality or when 25 years after randomization was achieved, whichever occurred first. For patients with ER+/PR‑/RAB6C+ tumors, prolonged distant recurrence‑free survival could not be observed if the patients were treated with tamoxifen [hazard ratio (HR), 1.82; 95% confidence interval (CI), 0.69‑4.79; P=0.23], whereas patients with ER+/PR‑/RAB6C‑ tumors had 75% reduced distant recurrence risk (HR, 0.25; 95% CI, 0.09‑0.70; P=0.008). In the ER+/PR+ subgroup, patients with RAB6C‑ and RAB6C+ tumors benefited from tamoxifen treatment, though it was most evident in the RAB6C+ group (HR, 0.27; 95% CI, 0.13‑0.58; P=0.001). The results of the present study indicated that, for patients with ER+/PR‑ tumors, those with low RAB6C expression benefited from tamoxifen treatment, whereas no benefit was observed in patients with high RAB6C levels.
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1 

Sant M, Chirlaque Lopez MD, Agresti R, Sánchez Pérez MJ, Holleczek B, Bielska-Lasota M, Dimitrova N, Innos K, Katalinic A, Langseth H, et al: Survival of women with cancers of breast and genital organs in Europe 1999-2007: Results of the EUROCARE-5 study. Eur J Cancer. 51:2191–2205. 2015.PubMed/NCBI View Article : Google Scholar

2 

Fredholm H, Magnusson K, Lindström LS, Garmo H, Fält SE, Lindman H, Bergh J, Holmberg L, Pontén F, Frisell J and Fredriksson I: Long-term outcome in young women with breast cancer: A population-based study. Breast Cancer Res Treat. 160:131–143. 2016.PubMed/NCBI View Article : Google Scholar

3 

Nordenskjöld A, Fohlin H, Fornander T, Löfdahl B, Skoog L and Stål O: Progesterone receptor positivity is a predictor of long-term benefit from adjuvant tamoxifen treatment of estrogen receptor positive breast cancer. Breast Cancer Res Treat. 160:313–322. 2016.PubMed/NCBI View Article : Google Scholar

4 

Gan L, Zuo G, Wang T, Min J, Wang Y, Wang Y and Lv G: Expression of WTH3 in breast cancer tissue and the effects on the biological behavior of breast cancer cells. Exp Ther Med. 10:154–158. 2015.PubMed/NCBI View Article : Google Scholar

5 

Cancer Genome Atlas Network: Comprehensive molecular portraits of human breast tumours. Nature 490: 61-70, 2012.

6 

Haverty PM, Fridlyand J, Li L, Getz G, Beroukhim R, Lohr S, Wu TD, Cavet G, Zhang Z and Chant J: High-resolution genomic and expression analyses of copy number alterations in breast tumors. Genes Chromosomes Cancer. 47:530–542. 2008.PubMed/NCBI View Article : Google Scholar

7 

Tian K, Wang Y and Xu H: WTH3 is a direct target of the p53 protein. Br J Cancer. 96:1579–1586. 2007.PubMed/NCBI View Article : Google Scholar

8 

Rutqvist LE and Johansson H: Stockholm Breast Cancer Study Group: Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer. Acta Oncol. 46:133–145. 2007.PubMed/NCBI View Article : Google Scholar

9 

Khoshnoud MR, Löfdahl B, Fohlin H, Fornander T, Stål O, Skoog L, Bergh J and Nordenskjöld B: Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen. Breast Cancer Res Treat. 126:421–430. 2011.PubMed/NCBI View Article : Google Scholar

10 

Jerevall PL, Jansson A, Fornander T, Skoog L, Nordenskjöld B and Stål O: Predictive relevance of HOXB13 protein expression for tamoxifen benefit in breast cancer. Breast Cancer Res. 12(R53)2010.PubMed/NCBI View Article : Google Scholar

11 

Thakkar JP and Mehta DG: A review of an unfavorable subset of breast cancer: Estrogen receptor positive progesterone receptor negative. Oncologist. 16:276–285. 2011.PubMed/NCBI View Article : Google Scholar

12 

Dowsett M, Houghton J, Iden C, Salter J, Farndon J, A'Hern R, Sainsbury R and Baum M: Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol. 17:818–826. 2006.PubMed/NCBI View Article : Google Scholar

13 

Bartlett JM, Brookes CL, Robson T, van de Velde CJ, Billingham LJ, Campbell FM, Grant M, Hasenburg A, Hille ET, Kay C, et al: Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: A prospectively powered pathology study in the Tamoxifen and Exemestane adjuvant multinational trial. J Clin Oncol. 29:1531–1538. 2011.PubMed/NCBI View Article : Google Scholar

14 

Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, et al: Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials. Lancet 378: 771-784, 2011.

15 

Bardou VJ, Arpino G, Elledge RM, Osborne CK and Clark GM: Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 21:1973–1979. 2003.PubMed/NCBI View Article : Google Scholar

16 

Viale G, Regan MM, Maiorano E, Mastropasqua MG, Dell'Orto P, Rasmussen BB, Raffoul J, Neven P, Orosz Z, Braye S, et al: Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol. 25:3846–3852. 2007.PubMed/NCBI View Article : Google Scholar

17 

Bostner J, Skoog L, Fornander T, Nordenskjöld B and Stål O: Estrogen receptor-alpha phosphorylation at serine 305, nuclear p21-activated kinase 1 expression, and response to tamoxifen in postmenopausal breast cancer. Clin Cancer Res. 16:1624–1633. 2010.PubMed/NCBI View Article : Google Scholar

18 

Young J, Ménétrey J and Goud B: RAB6C is a retrogene that encodes a centrosomal protein involved in cell cycle progression. J Mol Biol. 397:69–88. 2010.PubMed/NCBI View Article : Google Scholar

19 

Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, et al: Proteomics. Tissue-based map of the human proteome. Science. 347(1260419)2015.PubMed/NCBI View Article : Google Scholar

20 

Bhat S, Kabekkodu SP, Varghese VK, Chakrabarty S, Mallya SP, Rotti H, Pandey D, Kushtagi P and Satyamoorthy K: Aberrant gene-specific DNA methylation signature analysis in cervical cancer. Tumour Biol. 39(1010428317694573)2017.PubMed/NCBI View Article : Google Scholar

21 

Bhat S, Kabekkodu SP, Jayaprakash C, Radhakrishnan R, Ray S and Satyamoorthy K: Gene promoter-associated CpG island hypermethylation in squamous cell carcinoma of the tongue. Virchows Arch. 470:445–454. 2017.PubMed/NCBI View Article : Google Scholar

22 

Salavaty A, Motlagh FM, Barabadi M, Cheshomi H, Esmatabadi MJD, Shahmoradi M and Soleimanpour-Lichaei HR: Potential role of RAB6C-AS1 long noncoding RNA in different cancers. J Cell Physiol. 234:891–903. 2018.PubMed/NCBI View Article : Google Scholar

23 

Tian K, Wang Y, Huang Y, Sun B, Li Y and Xu H: Methylation of WTH3, a possible drug resistant gene, inhibits p53 regulated expression. BMC Cancer. 8(327)2008.PubMed/NCBI View Article : Google Scholar

24 

Shan J, Mason JM, Yuan L, Barcia M, Porti D, Calabro A, Budman D, Vinciguerra V and Xu H: Rab6c, a new member of the rab gene family, is involved in drug resistance in MCF7/AdrR cells. Gene. 257:67–75. 2000.PubMed/NCBI View Article : Google Scholar

25 

Shan J, Yuan L, Budman DR and Xu HP: WTH3, a new member of the Rab6 gene family, and multidrug resistance. Biochim Biophys Acta. 1589:112–123. 2002.PubMed/NCBI View Article : Google Scholar

26 

Fohlin H, Bekkhus T, Sandström J, Fornander T, Nordenskjöld B, Carstensen J and Stål O: RAB6C is an independent prognostic factor of estrogen receptor-positive/progesterone receptor-negative breast cancer. Oncol Lett. 19:52–60. 2020.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Fohlin H, Bekkhus T, Sandström J, Fornander T, Nordenskjöld B, Carstensen J and Stål O: Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer. Mol Clin Oncol 12: 415-420, 2020.
APA
Fohlin, H., Bekkhus, T., Sandström, J., Fornander, T., Nordenskjöld, B., Carstensen, J., & Stål, O. (2020). Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer. Molecular and Clinical Oncology, 12, 415-420. https://doi.org/10.3892/mco.2020.2014
MLA
Fohlin, H., Bekkhus, T., Sandström, J., Fornander, T., Nordenskjöld, B., Carstensen, J., Stål, O."Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer". Molecular and Clinical Oncology 12.5 (2020): 415-420.
Chicago
Fohlin, H., Bekkhus, T., Sandström, J., Fornander, T., Nordenskjöld, B., Carstensen, J., Stål, O."Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer". Molecular and Clinical Oncology 12, no. 5 (2020): 415-420. https://doi.org/10.3892/mco.2020.2014
Copy and paste a formatted citation
x
Spandidos Publications style
Fohlin H, Bekkhus T, Sandström J, Fornander T, Nordenskjöld B, Carstensen J and Stål O: Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer. Mol Clin Oncol 12: 415-420, 2020.
APA
Fohlin, H., Bekkhus, T., Sandström, J., Fornander, T., Nordenskjöld, B., Carstensen, J., & Stål, O. (2020). Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer. Molecular and Clinical Oncology, 12, 415-420. https://doi.org/10.3892/mco.2020.2014
MLA
Fohlin, H., Bekkhus, T., Sandström, J., Fornander, T., Nordenskjöld, B., Carstensen, J., Stål, O."Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer". Molecular and Clinical Oncology 12.5 (2020): 415-420.
Chicago
Fohlin, H., Bekkhus, T., Sandström, J., Fornander, T., Nordenskjöld, B., Carstensen, J., Stål, O."Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor‑positive/progesterone receptor‑negative breast cancer". Molecular and Clinical Oncology 12, no. 5 (2020): 415-420. https://doi.org/10.3892/mco.2020.2014
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