III. Non-operable locally advanced breast cancer: Stage III (except T3N1M0) The standard treatment steps for non-operable locally advanced breast cancer are as follows Step 1: Neoadjuvant chemotherapy: anthracycline-based ± paclitaxel-based regimen. If disease progression occurs during preoperative neoadjuvant therapy, palliative breast radiotherapy may be used to improve local control. Step 2: After preoperative neoadjuvant chemotherapy has achieved some clinical efficacy, some patients may undergo surgery. The surgery is either “total mastectomy + grade I/II axillary lymph node dissection ± delayed breast reconstruction” or “lumpectomy + grade I/II axillary lymph node dissection. Step 3: Postoperative adjuvant chemotherapy with the same protocol as adjuvant chemotherapy for operable early invasive breast cancer. Step 4: Both surgical approaches carry a high risk of local recurrence, therefore, postoperative radiotherapy to the chest wall and supraclavicular lymph nodes is performed. Radiotherapy should also be administered if the internal breast lymph nodes are involved. Step 5: Estrogen receptor-positive patients receive endocrine therapy. Long-term tamoxifen use in postmenopausal patients can lead to an increased risk of endometriosis, so it is advisable for patients to undergo endocrine therapy with an annual gynecologic physical examination. Stage IV metastatic or recurrent breast cancer 1. Simple local recurrence Patients who underwent total mastectomy should undergo resection of local recurrent lesions after local recurrence, followed by radiotherapy of the affected area and then systemic chemotherapy or endocrine therapy. For recurrent lesions in the chest that cannot be removed, radiotherapy should be given if no previous radiotherapy has been received. Patients with local recurrence after breast-conserving surgery should undergo total mastectomy followed by systemic chemotherapy or endocrine therapy. Some recent studies have shown that for patients with locally recurrent metastatic breast cancer, local tumor remission and duration of local tumor control are better than radiotherapy alone when heated on top of radiotherapy, but there is no difference in overall survival rate. 2.Systemic disease For breast cancer patients with distant metastasis, the aim of treatment is to prolong survival time and improve quality of life, not to cure. Therefore, less toxic treatment options should be chosen. Endocrine therapy: Patients with positive estrogen receptors should undergo endocrine therapy. For postmenopausal patients who have received anti-estrogen therapy and those within 1 year of anti-estrogen therapy, aromatase inhibitors are the first-line treatment of choice. The preferred second-line treatment options are oophorectomy or luteinizing hormone-releasing hormone agonists (e.g., goserelin) in combination with endocrine therapy. Aromatase inhibitors are slightly more effective than tamoxifen if no anti-estrogen therapy has been received and if previous anti-estrogen therapy has been given for more than 1 year, but the difference is not significant. Endocrine therapy in postmenopausal patients includes: selective nonsteroidal aromatase inhibitors (anastrozole and letrozole), steroidal aromatase inactivators (exemestane), simple antiestrogenic agents (fluvastatin), progesterone analogs (megestrol), androgens (fluorometholone), and massive estrogens (ethinyl estradiol). For premenopausal patients who have never received endocrine therapy, ovariectomy or pharmacological (goserelin) ovarian suppression followed by endocrine therapy as postmenopausal; or tamoxifen therapy. Endocrine therapy for premenopausal breast cancer patients includes: luteinizing hormone-releasing hormone agonists (goserelin and luprolide), ovariectomy, progesterone analogs (megestrol), androgens (fluoxymesterone), and large amounts of estrogen (ethinyl estradiol). Chemotherapy: Patients with the following advanced breast cancers should receive chemotherapy: ① estrogen receptor negative ② foci not limited to bone or soft tissue ③ with symptomatic visceral metastases ④ hormone receptor positive but resistant to endocrine therapy. Compared with single-agent chemotherapy, combination chemotherapy usually has a higher objective remission rate and a longer time from remission to disease progression. However, combination chemotherapy is associated with greater toxicity and less survival benefit. The clinical standard of care is to apply first-line treatment regimens until disease progression. Bisphosphonate therapy for patients with bone metastases: For breast cancer patients with bone metastases, bisphosphonates (e.g., ibant phosphate or zolay phosphate) should be given in combination with calcium citrate and vitamin D therapy. Bisphosphonates should be given in addition to chemotherapy or endocrine therapy. In cases of osteolytic breast cancer metastases, zolay phosphate may be more effective than pamiphos. Bisphosphonates for bone metastases are palliative measures and treatment may result in fewer bone-related events and reduce the need for radiotherapy or surgery for bone pain. Iban phosphate or zolay phosphate may be given at a dose of 4 mg once every 3 to 5 weeks in combination with antitumor therapy. Bisphosphonate therapy requires concomitant calcium and vitamin D supplementation at doses of 1200-1500 mg/d of calcium and 400-800 IU/d of vitamin D3, respectively.