The Effect of Supplemental Interval Training on a Stationary Bike on Treatment Response in Women with Early-Stage Triple-Negative Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by the uncontrolled proliferation of mammary gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the stage of the disease, the tumor’s growth rate (Ki-67 index), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of HER2 receptors on the cells (HER2-positive).

Triple-negative breast cancer is an aggressive form of breast cancer that lacks hormone receptors and HER2 receptors. Today, the standard of care is usually neoadjuvant combination therapy consisting of chemotherapy and immunotherapy (e.g., pembrolizumab), followed by surgery. Neoadjuvant means that this treatment is administered before surgery. The goal is to eliminate the tumor as completely as possible before surgery. This is called “pathological complete remission (pCR),” meaning no evidence of invasive cancer cells in the breast or the removed lymph nodes, and is considered a good prognostic sign.

The aim of this study is to investigate whether supplemental high-intensity interval training (HIIT) activates the immune system and improves blood flow in the tumor, thereby increasing the effectiveness of immuno-chemotherapy. As part of the study, patients will be randomly assigned to two groups. Both groups will receive the same therapy via infusion: the drugs paclitaxel plus carboplatin weekly for 12 weeks and pembrolizumab every 3 weeks (4 cycles), followed by epirubicin and cyclophosphamide every 3 weeks (4 cycles each) plus pembrolizumab every 3 weeks (4 cycles). The intervention group also receives supervised, twice-weekly HIIT cycling sessions over approximately 6 months (each lasting about 60 minutes, alternating between 30 seconds of interval exercise at approximately 90% of maximum power and 30 seconds of light pedaling, including warm-up and cool-down). In some cases, the sessions are conducted approximately one hour before the infusion. The study includes a blinded endpoint assessment, meaning the evaluation is conducted without knowing which group the patient belonged to. The primary endpoint is pathological complete remission following completion of neoadjuvant therapy and surgery. Secondary endpoints include, among others, tumor response as assessed by ultrasound (every 3 weeks), cardiopulmonary fitness (spiroergometry), biomarkers of the immune response, ocular vascular measurements (OCTA), quality of life, fatigue, tolerability, as well as progression-free survival and overall survival (up to 3 years).

Eligible participants are women aged 18 to 85 with newly diagnosed, histologically confirmed, and ultrasound-measurable triple-negative breast cancer (stages T1cN1–2 or T2–4N0–2), who are eligible for neoadjuvant immunochemotherapy with paclitaxel/carboplatin plus pembrolizumab, followed by epirubicin/cyclophosphamide plus pembrolizumab. Women of childbearing age must use adequate contraception. Patients with medical conditions that preclude physical activity, such as severe heart failure, are not eligible to participate in the study.