Effectiveness of tocotrienol-rich fraction combined with tamoxifen in the management of women with early breast cancer: a pilot clinical trial

Kalanithi Nesaretnam, Kanga Rani Selvaduray, Ghazali Abdul Razak, Sheela Devi Veerasenan, Patricia A Gomez, Kalanithi Nesaretnam, Kanga Rani Selvaduray, Ghazali Abdul Razak, Sheela Devi Veerasenan, Patricia A Gomez

Abstract

Introduction: Basic research has indicated that tocotrienols have potent antiproliferative and proapoptotic effects that would be expected to reduce the effect of breast cancer.

Methods: We conducted a double-blinded, placebo-controlled pilot trial to test the effectiveness of adjuvant tocotrienol therapy in combination with tamoxifen for five years in women with early breast cancer. Two-hundred-forty women, aged between 40-60 years, with either tumor node metastases (TNM) Stage I or II breast cancer and estrogen receptor (ER) positive tumors were non-randomly assigned to two groups. The intervention group received tocotrienol rich fraction (TRF) plus tamoxifen whilst the control group received placebo plus tamoxifen, for five years.

Results: During the five years of study, 8 patients died due to breast cancer while 36 patients developed local or systemic recurrence. Five-year breast cancer specific survival was 98.3% (95% confidence interval (CI): 95.9% to 100%) in the intervention group and 95%, (95% CI: 91.1% to 98.9%) in the control group, while 5-years disease free survival was 86.7% (95% CI: 80.6% to 92.8%) and 83.3% (95% CI: 76.6% to 90.0%), respectively. Risk of mortality due to breast cancer was 60% (HR: 0.40; 95% CI: 0.08 to 2.05) lower in the intervention group versus the controls following adjustment for age, ethnicity, stage and lymph node status but this was not statistically significant. Adjuvant TRF therapy was not associated with breast cancer recurrence (HR: 0.84; 95% CI: 0.43-1.65).

Conclusions: From the current study, there seems to be no association between adjuvant tocotrienol therapy and breast cancer specific survival in women with early breast cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT01157026.

Figures

Figure 1
Figure 1
Flow diagram of the progress through the phases of the parallel trials of two groups (enrolment, intervention allocation, follow-up, and data analysis).
Figure 2
Figure 2
Breast cancer-specific survival in intervention versus control group.
Figure 3
Figure 3
The α-tocopherol, α-, γ-, and δ-tocotrienol concentrations increased significantly after 5 years for the TRF-supplemented group. *P < 0.05.

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