Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer
Effect of Huaier Granule on Adjuvant Treatment for High-risk Early-stage Triple-negative Breast Cancer
This is a prospective, multicenter, randomized, parallel controlled, open-label study. The
 primary purpose of this study is to evaluate the efficacy of Huaier Granule on postoperative
 adjuvant therapy of high-risk early-stage triple-negative invasive ductal carcinoma. The
 Secondary purposes are to evaluate the safety of long-term use of Huaier granules as
 postoperative adjuvant treatment of high-risk early-stage triple-negative invasive ductal
 carcinoma, and the changes of quality of life score after treatment with Huaier granule.
Triple-negative breast cancer（TNBC） accounts for 10% to 20% of breast cancer. TNBC is more
 likely to show lymph node involvement at diagnosis, and biologically more aggressive. Women
 with TNBC have a higher rate of distant recurrence at early-stage and a worse 5-year
 prognosis than women of other molecular types. Although PARP inhibitors and immune checkpoint
 inhibitors are showing promise to patients with advanced TNBC, however, these targeted
 therapies and immunotherapy for TNBC can not increase the clinical benefits of early-stage
 patients.

 As adjuvant therapy for hepatocellular carcinoma after curative liver resection, a
 multicentre study demonstrated a significant prolongation of RFS and reduced extrahepatic
 recurrence in Huaier group. Retrospective studies have shown that Huaier granules can improve
 the rates of disease-free survival（DFS） and overall survival（OS）, and reduce the incidence of
 adverse events among operable patients with TNBC.

 In this study, 1072 high-risk early-stage triple-negative invasive ductal carcinoma
 participants (536 cases in the observation group and 536 cases in the control group) from 30
 research centers will be included. The block randomization was adopted, participants will be
 randomly divided into the experimental group (Huaier granule plus conventional
 treatment/visit) and control group (conventional treatment/visit only). All participants will
 be followed up for 5 years, including 2-year treatment follow-up and 3-year survival
 follow-up. During the treatment period, the participants will be followed up every 3 months,
 and the survival follow-up period will be followed up every 6 months.
Inclusion Criteria:

 1. Aged from 18 to 70.

 2. Histologically confirmed as breast invasive ductal carcinoma.

 3. Molecular typing of breast lesions is triple-negative breast cancer, when the patient
 had multicentric lesions at the same time, all invasive lesions were confirmed as
 triple-negative.

 4. Regional lymph node metastasis confirmed by postoperative pathology [except isolated
 tumor cells ( ITC )], or tumor response did not achieve pathological complete response
 (pCR) after neoadjuvant therapy [neoadjuvant chemotherapy completed at least four
 cycles, the breast has residual invasive cancer or axillary lymph node metastasis (
 except isolated tumor cells ) .]

 5. There was no local recurrence and distant metastasis of the tumor.

 6. The time of randomization is during the postoperative adjuvant therapy or within 60
 days after the end of the last postoperative adjuvant therapy.

 7. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1.

 8. Hepatic function and renal function: serum creatinine level ≤ 1.5 × upper limit of
 normal (ULN), aspartate aminotransferase (AST) concentration / alanine
 aminotransferase (ALT) concentration≤ 2.5 × ULN，total serum bilirubin concentration≤
 1.5 × ULN.

 9. Blood routine: neutrophil count ≥ 1.5*109 / L, platelet count ≥ 100*109 / L,
 hemoglobin concentration ≥ 90 g / L (without transfusion).

 10. The participants volunteered to join the study with good compliance and signed an
 informed consent form.

 Exclusion Criteria:

 1. Bilateral breast cancer.

 2. Complicated with severe cardiopathy, hepatopathy, nephropathy, endocrine system
 diseases. According to the researchers' judgement, the comorbidities can cause
 unacceptable safety risks and affect participants' compliance with research programs.

 3. Suffering from malignant tumors other than breast cancer (except cured basal cell
 carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years.

 4. Allergic to Huaier granule.

 5. Pregnant or lactating women, and those who planning a pregnancy during the study
 period.

 6. Participating in other clinical trials or participated in other clinical studies
 within 3 months.

 7. Patients with a poor compliance, or they are not appropriate for this study because of
 other reasons considered by the researchers.