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

Fohlin,Helena; Bekkhus,Tove; Sandström,Josefine; Fornander,Tommy; Nordenskjöld,Bo; Carstensen,John; Stål,Olle

doi:10.3892/mco.2020.2014

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
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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
Published online on: March 9, 2020 https://doi.org/10.3892/mco.2020.2014
Pages: 415-420
Copyright: © Fohlin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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