Effect of concomitant use of pitavastatin with neoadjuvant chemotherapy protocols in breast cancer patients: A randomized controlled clinical trial

Samar A Dewidar, Omar Hamdy, Ahmed Eltantawy, Mohamed El-Mesery, Amal M El Gayar, Moetaza M Soliman, Samar A Dewidar, Omar Hamdy, Ahmed Eltantawy, Mohamed El-Mesery, Amal M El Gayar, Moetaza M Soliman

Abstract

Introduction: Preclinical studies have demonstrated the possible anticancer effects of statins, but the synergistic effect of concomitant statin use with standard chemotherapy protocols in patients with breast cancer has not yet been investigated.

Aim: The current study aimed to evaluate the efficacy of concomitant pitavastatin use with neoadjuvant chemotherapy protocols in patients with breast cancer.

Methods: This study was a randomized controlled clinical trial. A total of 70 adult female patients with pathologically-proven invasive breast cancer were randomized to receive or not receive pitavastatin (2 mg) oral tablets once daily concomitantly with standard neoadjuvant chemotherapy protocols for 6 months. The primary outcomes of this study were changes in tumor size and changes to the Ki67 index. In addition, secondary outcomes were changes in cyclin D1 and cleaved caspase-3 serum levels. This study was registered at ClinicalTrials.gov (Identifier: NCT04705909).

Results: Patients in the pitavastatin group showed significantly higher median (IQR) reductions in tumor size [-19.8 (-41.5, 9.5)] compared to those in the control group [-5.0 (-15.5, 0.0), p = 0.0009]. The change in Ki67 from baseline to the end of therapy was similar between the two groups (p = 0.12). By the end of therapy, the cyclin D1 levels in the pitavastatin group were significantly decreased [median (IQR) change of - 10.0 (-20.2, -2.9) from baseline], whereas the control group showed an increase in cyclin D1 levels [14.8 (4.1, 56.4)]. The median (IQR) caspase-3 was elevated in the pitavastatin group 1.6 (0.2, 2.2), and decreased in the control group (-0.2 (-1.1, 0.0), p = 0.0002).Subgroup analysis of the pitavastatin group revealed that patients with positive human epidermal growth receptor 2 (HER2) had higher median (IQR) reductions in Ki67 [-35.0 (-70.0, -12.5)] than those with negative HER2 [2.5 (-15.0, 10.0), p = 0.04]. All patients who achieved a complete pathological response (n = 9) exhibited an HER2-neu positive receptor at baseline.

Conclusion: Concomitant use of pitavastatin with standard neoadjuvant chemotherapy protocols may improve neoadjuvant chemotherapy responses in patients with breast cancer.

Keywords: Caspase-3; Cyclin D1; Hormone receptor; Ki67; Statins; Synergistic action; Tumor response; Tumor size.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2022 The Author(s).

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Flow diagram of patients screening, recruitment, and follow up. * The standard neoadjuvant chemotherapy protocol (doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel).
Fig. 2
Fig. 2
Ki67 (A), tumor size (B), cyclin D1 levels (C), and caspase-3 levels (D) before and after therapy in pitavastatin and control groups. * Significant difference (p ≤ 0.05), and ns. non-significant.
Fig. 3
Fig. 3
Type of pathological response achieved in study patients according to baseline HER2 receptors (A) and the molecular tumor types (B).

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