In advanced breast cancer, the incidence of bone metastasis is 65%~75%, and the first symptom of bone metastasis accounts for 27%~50%. The vertebral body is the common site of bone metastasis of breast cancer, accounting for about 50%, followed by ribs, pelvis, skull, humerus, femur, tibia-fibula and scapula, etc. Bone metastases are mainly manifested as osteolytic lesions. Pain is the first symptom of most bone metastases, with an incidence of >80%, and some of the lesions are small enough to cause pain. Bone radionuclide scan (ECT) is used for routine primary diagnosis of suspected bone metastases in breast cancer presenting with bone pain, fracture, elevated alkaline phosphatase, hypercalcemia, etc. MRI, CT and X-ray are the confirmatory imaging tests for bone metastases. Some studies have shown that PET/CT has similar sensitivity and higher specificity to ECT and can be used for follow-up of breast cancer bone metastases after treatment. If necessary, a bone biopsy is needed to obtain a pathological diagnosis.
The most common complications of breast cancer bone metastases are bone-related events (SREs), defined as increased bone pain or the development of new bone pain, pathological fractures, vertebral compression or deformation, crestal medullary compression, post-radiotherapy symptoms of bone, and hypercalcemia. Bone metastases from breast cancer are characterized by SREs that often severely affect the patient’s autonomic activity and quality of life, but bone metastases themselves are generally not directly life-threatening and patients without concomitant visceral metastases have relatively long survival.
The goals of treatment for breast cancer bone metastases are.
① prevention and treatment of SREs.
②relieve pain.
③ restoring function and improving quality of life.
④ control tumor progression and prolong survival.
Breast cancer bone metastasis, which has been treated as a systemic disease, therefore requires an individualized and comprehensive treatment plan based on the patient’s specific condition.
The treatment options available are.
(i) chemotherapy, endocrine therapy, and molecular targeted therapy for the treatment of the underlying primary tumor in metastatic breast cancer.
(ii) Bone modifying drug therapy (bisphosphonates, denosumab), mainly for the prevention and treatment of SREs.
(iii) surgical treatment for the aggressive treatment of single or limited bone metastatic lesions.
(iv) Radiotherapy, for local treatment, is preferred.
⑤ analgesia and other supportive treatments.
Chemotherapy, endocrine therapy and molecular targeted therapy
are the basic drug treatments for recurrent metastatic breast cancer. The selection of treatment plan for recurrent metastatic breast cancer takes into account the hormone receptor status (ER/PR) of the patient’s tumor tissue, HER-2 status, age, menstrual status, and whether the disease is progressing slowly. In principle, endocrine therapy can be preferred for patients with hormone-responsive breast cancer with slow disease progression, chemotherapy should be preferred for patients with recurrent metastases with rapid disease progression, and trastuzumab-containing regimens should be considered for patients with HER-2 overexpression. Based on the fact that breast cancer bone metastases generally do not pose a direct life threat and patients without combined visceral metastases have a relatively long survival, unnecessary and intense chemotherapy should be avoided as much as possible. Patients with breast cancer bone metastases, such as those with negative ER and PR, short disease-free postoperative interval, rapid disease progression, combined visceral metastases, and those who do not respond to endocrine therapy should be considered for chemotherapy.
Radiotherapy
Radiotherapy is an effective method for palliative treatment of breast cancer bone metastases. The main role of radiotherapy in the treatment of breast cancer bone metastases is to relieve bone pain and reduce the risk of pathological fracture. Radiation therapy includes external irradiation and radionuclide therapy.
Surgical treatment
Whether to choose surgical treatment and which surgical treatment method to choose are questions clinicians often face. Most importantly, early detection of bone metastases and assessment of the risk of potential pathologic fractures of the long bones and crest. Indications for surgery for breast cancer bone metastases: expected survival greater than 4 weeks, pathologic fracture or crestal medullary compression, bone lesions greater than 2.5 cm in diameter, and greater than 50% cortical destruction.
Analgesic treatment
NSAIDs are the basis of pain management for bone metastases. When pain relief is not effective or moderate to severe pain is present, a combination of opioid analgesics is recommended. Timely application of opioid extended-release agents is beneficial for sustained pain relief. The on-time dose of analgesics can be increased for frequent episodes of sudden pain. The main method of controlling sudden onset pain is to spare fast-acting or short-acting analgesics, and the single dose is usually 5% to 10% of the daily dose. For patients with refractory sudden pain, patient-controlled drug pump administration may be considered.
Clinical application of bisphosphonates
Bisphosphonates are stable analogs of pyrophosphonate molecules that inhibit osteoclast-mediated bone resorption, as well as osteoclast maturation, inhibit the function of mature osteoclasts, inhibit osteoclast aggregation at sites of bone resorption, and inhibit tumor cell spreading, infiltration, and adhesion to the bone matrix. Clinical studies have confirmed that bisphosphonates can effectively treat breast cancer bone metastases and reduce the incidence of SREs. Blood calcium, creatinine, phosphorus and magnesium levels should be tested before intravenous bisphosphonate or subcutaneous denosumab injection. Since hypophosphatemia and hypocalcemia are likely to occur during treatment, it is recommended that calcium, phosphorus, and magnesium levels should be monitored more frequently during treatment. Both bisphosphonate and denosumab treatment may cause osteonecrosis of the jaw, with an incidence of 3 per 1,000 in breast cancer patients; therefore, patients should be recommended to have a dental examination before bisphosphonate or denosumab injection, and dental procedures should be avoided during treatment if possible. Long-term treatment with bisphosphonates should be supplemented with calcium and vitamin D at doses of 1200-1500 mg of calcium and 3400-800 U of vitamin D daily.