mTOR Levels and Metastasis in Luminal Breast Cancer: Implications for Prognosis and Treatment

Articles in Press

Document Type : Research Articles

Authors

1 Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

2 Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

3 Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia.

4 Hasanuddin University Hospital, Makassar, Indonesia.

Abstract

Background: Breast cancer (BC) is the most common cancer in women, with metastasis being the leading cause of mortality. The PI3K/PTEN/Akt/mTORC1 signaling pathway plays a crucial role in cancer cell proliferation, angiogenesis, and invasion, with mammalian target of rapamycin (mTOR) serving as a key regulator. Activation of mTOR is associated with tumor growth and resistance to therapy in luminal and human epidermal growth factor receptor 2 positive (HER2-positive) BC subtypes. This study aims to explore the relationship between serum mTOR levels and metastasis in luminal, HER2-positive and HER2-negative BC subtypes to assess the potential of mTOR as a predictive biomarker and therapeutic target. Methods: This preliminary cross-sectional study included BC patients with luminal HER2-positive or HER2-negative subtypes. Serum mTOR levels were measured using a Human ELISA kit. The optimal cut-off point for mTOR was determined using a Receiver Operating Characteristic (ROC) curve analysis. Statistical associations between mTOR levels and metastasis were performed using the Chi-square or Fisher’s exact test, and the prevalence ratio (PR) with a 95% confidence interval was calculated. Results: The ROC curve demonstrated an AUC of 0.996, with an optimal cut-off point for serum mTOR levels at 13.32 ng/mL, showing 100% sensitivity and 96.4% specificity for predicting metastasis. The mean mTOR level was 58.39±250.91 ng/mL, with 50% exhibiting elevated levels (≥13.32 ng/mL). Notably, mTOR levels were significantly higher in HER2-positive cases (113.59±381.87 ng/mL) compared to HER2-negative cases (17.45±14.83 ng/mL; p=0.040). Elevated mTOR levels were significantly associated with metastasis (p<0.001), with a PR of 0.037 (95% CI: 0.005-0.253). Conclusions: Increased serum mTOR levels (≥13.32 ng/mL) are significantly linked to the presence of metastasis, particularly in HER2-positive BC. These findings suggest serum mTOR as a promising biomarker for metastasis risk and a potential therapeutic target in luminal BC.

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Asian Pacific Journal of Cancer Prevention

Articles in Press, Accepted Manuscript
Available Online from 12 September 2025

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History

  • Receive Date: 24 February 2025
  • Revise Date: 16 June 2025
  • Accept Date: 06 September 2025

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