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

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-/RAB6Ctumors 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 RAB6Cand 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 + /PRtumors, those with low RAB6C expression benefited from tamoxifen treatment, whereas no benefit was observed in patients with high RAB6C levels.

Long Non-Coding RNAs Expression in Breast Cancer: CBR3-AS1 LncRNA as a Sensitive Biomarker

“…In another study, RAB6C-AS1 is reported as an inhibitor for proliferation, invasion, and metastasis and acts as a tumor suppressor similar to p53 (Fohlin et al, 2020). It is claimed that low expression of RAB6C-AS1 (Fohlin et al, 2020).…”

“…In another study, RAB6C-AS1 is reported as an inhibitor for proliferation, invasion, and metastasis and acts as a tumor suppressor similar to p53 (Fohlin et al, 2020). It is claimed that low expression of RAB6C-AS1 (Fohlin et al, 2020). They conclude that, ER+/PR-tumors with low RAB6C expression could have better outcome by tamoxifen treatment versus those with high RAB6C expression.…”

MiR-640 and MiR-525-5p as Relapse-Associated MicroRNAs in Systematically Untreated Individuals with Low-Risk Primary Breast Cancer

“…Freshly frozen tumor biopsies were collected from individuals (n = 180) who were diagnosed with low-risk primary breast cancer by pathological examination with no lymph node metastases and a tumor diameter ≤ 3 cm (Fohlin et al 2020)…”

Stratification of Estrogen Receptor-Negative Breast Cancer Patients by Integrating the Somatic Mutations and Transcriptomic Data

“…Due to the lack of reliable biomarkers, it is impossible to identify ER − tumors with a good prognosis (Teschendorff et al, 2007;Zhang et al, 2016). Several studies have revealed that different chromosomal and gene expression patterns are present in patients with different estrogen receptor statuses (Zhang et al, 2009;Fohlin et al, 2020). Thus, an accurate grouping of ER − breast cancer into clinically relevant subtypes is of particular importance for therapeutic decision making.…”