Clinical Application of Vagus Nerve Stimulation Combined With Immunoregulatory T Cells in Alleviating Aromatase Inhibitor-Induced Pain

Inclusion Criteria:

1. Female participants aged over 18 years;
2. Patients with pathologically confirmed stage I-III primary breast cancer;
3. Patients who have recovered from systemic symptoms related to surgery, radiotherapy, or chemotherapy;
4. Patients with estrogen receptor- and/or progesterone receptor-positive breast cancer who are receiving aromatase inhibitor therapy and have aromatase inhibitor-related musculoskeletal pain, with a score greater than 3 on the Worst Pain item of the Brief Pain Inventory (BPI-WP);
5. Patients who have received aromatase inhibitor therapy for more than 30 days and are expected to continue treatment for more than 1 year;

6. Patients who voluntarily agree to participate in this study and sign the informed consent form.

   For participants receiving combined IL-2 treatment, the following additional criterion applies:

7. Pain relief rate of less than 50% after taVNS treatment and a lower peripheral blood Treg count than before treatment.

Exclusion Criteria:

1. Patients with advanced breast cancer;
2. Patients with other significant organ dysfunction, such as major cardiovascular disease, diabetes mellitus, or hyperthyroidism;
3. Patients with other cancers;
4. Patients with a history of fracture or surgery around the painful joint area within the past 6 months;
5. Patients currently receiving corticosteroids or opioid therapy;
6. Patients with contraindications to vagus nerve stimulation;
7. Patients who are unable to communicate normally, such as those with cognitive impairment or hearing impairment;

8. Patients who have participated in another clinical trial within the past 1 month.

   For participants receiving combined IL-2 treatment, the following additional exclusion criteria apply:

9. Severe cardiac or renal disease, or hematologic disease;
10. Previous IL-2-related toxic reaction or allergy;
11. Use of other biologic agents or immunosuppressive drugs within the past 1 month;
12. Any other condition that the investigator considers unsuitable for study participation.