Breast cancer is the most commonly diagnosed cancer globally and the leading cause of cancer-related deaths among women [1]. The cure for breast cancer becomes impossible when it develops into an advanced stage. Therefore, the key factors for enhancing clinical outcomes in breast cancer revolve around early detection, curative resection, and effective adjuvant or neoadjuvant therapy.
Substantial improvements have been made in systemic therapies for advanced breast cancer (ABC), including targeted therapy, hormonal therapy, and immunotherapy; however, chemotherapy remains the cornerstone for ABC and early breast cancers (EBC) as well. Adjuvant chemotherapy in EBC reduces recurrence risk and breast cancer mortality [2]. Nevertheless, chemotherapy is associated with numerous adverse events (AEs), including nausea, vomiting, mucositis, bone marrow suppression, alopecia, peripheral neurotoxicity, and fatigue.
Owing to concerns about AEs associated with chemotherapy, many patients hesitate to accept neoadjuvant or adjuvant chemotherapies. Some patients even allow their tumors to progress from EBC to ABC. Therefore, addressing and mitigating AE severity from chemotherapy constitutes crucial aspects of supportive care.
Various methods have been implemented to ameliorate AEs from chemotherapy, such as granulocyte colony-stimulating factor for leukopenia, 5-hydroxytryptamine receptor type 3 antagonist for emesis, and modifying the administration schedule from triweekly to weekly. Despite these efforts, fatigue remains a challenge with no good treatment.
A nationwide survey in Taiwan revealed that cancer-related fatigue (CRF) was among the most common symptoms for advanced cancers, including breast cancer [3]. Fatigue is a common AE from neoadjuvant or adjuvant therapy for ABC, either with chemotherapy alone [4, 5], in combination with a targeted therapy [6, 7], or with immunotherapy, where the incidence can exceed 35% [8, 9].
Astragalus polysaccharides (PG2, PhytoHealth Corp., Taiwan) injection has been approved as a pharmacotherapy for treating CRF in patients with advanced cancer in Taiwan. In a pivotal trial, PG2 improved CRF among patients with advanced cancer [10]. Subsequently, a phase 4 study further validated PG2 efficacy in improving fatigue scores for patients with advanced cancer, especially those with breast cancer [11].
Numerous translational and clinical studies have provided evidence of the synergistic effects of PG2 with anticancer therapies such as chemotherapy, target therapy, and immunotherapy [12]. Additionally, studies have highlighted PG2 immunomodulation effects [13].
In our study, we aimed to evaluate the efficacy of PG2 as a complementary treatment for patients with stage II/III EBC undergoing adjuvant chemotherapy with epirubicin and cyclophosphamide (EC) regimen. The goal was to investigate whether PG2 could reduce chemotherapy-induced fatigue (CIF), minimize toxicity, and enhance compliance to chemotherapy. The primary endpoint involved evaluating the change in the fatigue global score (FGS) using the brief fatigue inventory (BFI)-Taiwan [14] during the first four EC cycles. The secondary endpoints included chemotherapy dose reductions and delays, the incidence of grade 3/4 hematologic toxicities based on the Common Terminology Criteria for AE 4.03, Eastern Cooperative Oncology Group performance status, and health-related quality of life (HRQL) using the Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 (EORTC QLQ-C30 & BR23) [15], during the first four EC cycles.