Effect of Ruai-Sanyin formula maintenance therapy after completion of standard adjuvant treatment on survival in women with early-stage triple negative breast cancer: A multicenter prospective cohort study

Background Ruai-sanyin formula (RASYF) is composed of a variety of anticancer herbs. It is widely used in the treatment of triple negative breast cancer (TNBC) and has proved to inhibit tumor growth and lung metastasis in animal models, but there is no evidence for clinical application in the real world. Methods We conducted this prospective cohort study at 5 research centers in China from November 2016 to December 2018. RASYF was set as an exposure factor. TNBC patients within 3 months after completion of standard adjuvant treatment were included. The exposed group received RASYF treatment, while the non-exposed group received observation. The primary end point was disease-free survival (DFS). Secondary end points included, overall survival (OS), distant disease-free survival (DDFS), relapse-free survival (RFS), QLQ-BR23 assesses quality of life in patients and adverse events. Results A total of 613 eligible patients with operable TNBC were enrolled, of which 588 were included in the Full Protocol Set. At a median follow-up of 48 months, DFS time was longer in those assigned to RASYF compared with observation (3-year DFS, 89.6% vs. 83.5%, [HR = 0.61, 95%CI (0.39-0.95)]; P = 0.03). Similar outcomes were observed for RFS (3-year RFS, 92.1% vs. 85.9%, HR = 0.55, [95% CI, 0.34-0.91]; P = 0.02). However, there was no statistically significant difference in OS and DDFS between the groups. In exploratory subgroup analysis, RASYF benefits were greater in patients with age under the 40 (3-year DFS, 88.4% vs. 76.1%, [HR = 0.45, 95%CI (0.21-0.95)]; P = 0.03). And RASYF is helpful to the improvement of postoperative quality of life. Comparing to the observation group, RASYF increased the mean CFB of BR23 scores in body image (12.34 vs. 8.76, P = 0.03)，sexual function (11.79 vs. 9.23, P P= 0.04), and decreased the scores of systemic therapy side effects (-12.41 vs. -9.24, P = 0.01). Safety analysis showed that RASYF caused major adverse reactions including impaired liver function (4.0%) and stomach pain (6.1%), but the overall security is controllable. Conclusion RASYF supplementation for 2 years after standard adjuvant chemoradiotherapy has certain clinical significance in preventing recurrence and metastasis and improving the quality of life of patients with early TNBC. Trial registration ClinicalTrials.gov: NCT03332368 Registered 6 November, 2017 (retrospectively registered)