Breast cancer is the most common malignancy in women, with approximately 1.4 million new cases per year worldwide. Given the malignant biological behavioral characteristics of breast cancer, local recurrence with distant metastasis will mostly occur eventually.
Breast cancer metastasis is organ-selective, and the incidence of bone metastasis in advanced breast cancer is 65-70%, while the first symptom is bone metastasis in 27%-50% of patients. The vertebral body is the common site of bone metastasis of breast cancer, about 50%, followed by ribs, pelvis, skull and humerus.
Bone metastasis sites mainly present as osteolytic lesions. Pain is the first symptom of most bone metastases, with an incidence of >80%, and some of the lesions are very small. For breast cancer patients, if only bone metastases occur, the prognosis is relatively good.
Bone metastases from breast cancer often cause a series of bone-related events such as intractable bone pain, hypercalcemia, pathological fracture and functional impairment, which can seriously affect the quality of life and even lead to death.
I. Diagnosis of bone metastasis
1.Bone radionuclide scan is used for routine initial screening diagnosis of suspected bone metastases such as bone pain, fracture, elevated alkaline phosphatase and hypercalcemia in breast cancer.
2.MRI, CT and X-ray are used to confirm the diagnosis of bone metastasis.
3.PET/CT is better than bone scan for the follow-up of breast cancer bone metastases after treatment, but it is not routinely recommended clinically.
4.Bone biopsy is needed to obtain pathological diagnosis when necessary.
Treatment strategy
The goals of treatment for breast cancer bone metastases are to prevent and treat SREs, relieve pain, restore function, improve quality of life, control tumor progression and prolong survival.
Breast cancer bone metastasis is a systemic disease, and its treatment is also based on systemic treatment. Chemotherapy, endocrine therapy, targeted therapy and bisphosphonates can prevent and treat SREs.
Reasonable local treatment can better control the symptoms of bone metastases, among which surgery is an active means to treat single bone metastases and radiotherapy is an effective local treatment.
Radiation therapy Radiation therapy is an effective method of palliative treatment for breast cancer bone metastases, and its ability to prevent or alleviate symptoms or functional impairment brought about by bone metastatic lesions during the survival time of tumor patients.
The main role of radiation therapy for the treatment of breast cancer bone metastases is to relieve bone pain and reduce the risk of pathological fractures. The effectiveness of treatment can be greatly improved by combining with bisphosphonates and antitumor therapy drugs targeting molecular typing.
1. Main indications for extracorporeal irradiation.
Symptomatic bone metastases for pain relief and restoration of function; selective prophylactic radiotherapy for weight-bearing bone metastases, such as spine or femur metastases. Common dose and segmentation method: 300 cGy/session, 10 times; 400 cGy/session, 5 times; 800 cGy/session, single irradiation.
2.Radionuclide therapy.
Osteophilic radionuclides that can emit β-rays through veins and have suitable half-life are introduced into the body to concentrate and release rays at the site of bone metastasis, thus relieving pain and killing the tumor. Radionuclide therapy is effective in relieving the pain of widespread systemic bone metastases, but some radionuclides have a high incidence of bone marrow suppression after treatment. Clinical use should be fully considered to select appropriate cases and proper timing.
The effective rate of radiotherapy to relieve bone pain is 59%~88%. For patients before radiation therapy is apparently effective and for patients whose pain is not completely controlled by radiation therapy, pain medication and, if necessary, bisphosphonate therapy are still required depending on the patient’s pain level.
Surgical treatment surgical treatment can maximize the problem of bone strength loss, pathological fracture and tumor compression of nerves in patients with bone metastases from breast cancer, and can reduce pain, restore limb function and improve patients’ quality of life.
Patients with bone metastases should be closely followed up and observed to detect bone metastases at an early stage, make proper judgment on whether long bones with potential pathological fractures need surgery, and strive for effective surgical treatment before fracture and paraplegia.
III. Surgical treatment of bone metastases from breast cancer includes
1.Simple internal fixation.
2.Lesion removal plus internal fixation.
3.Local excision plus artificial joint replacement.
4.Decompression and reconstruction of spinal stability after spinal cord compression. Fixation therapy can be considered selectively for the treatment of pathological fractures or for patients with bone metastases from breast cancer with expected survival time >3 months after decompression due to spinal cord compression.
Prophylactic fixation therapy may be considered electively for patients with bone metastases from breast cancer who have an expected survival time > 3 months and who have
1. Femoral metastases >2.5 cm in length and diameter.
2. Bone metastasis in the femoral neck.
3. Bone cortical destruction > 50%.
Analgesic treatment pain medication is the main method to relieve the pain of breast cancer bone metastasis. The pain medication treatment of bone metastasis pain should follow the World Health Organization three-step cancer pain relief guideline.
1. Oral and non-invasive routes of administration are preferred.
2. Give the medication according to the steps.
3. Timely administration.
4. Individualized administration.
5.Pay attention to specific details.
Non-steroidal anti-inflammatory drugs are the basic drugs for pain management of bone metastasis pain medication. When the pain relief effect is not good or moderate to severe pain occurs, the combination of opioid analgesics is recommended.
The choice of opioid extended-release agents for timely dosing facilitates sustained relief of bone pain.
Persistent chronic pain is associated with sudden onset of pain in approximately 63% of patients with bone metastases. For frequent episodes of sudden pain, the pain can be relieved by increasing the dose of analgesic medication on time.
The main method of controlling sudden pain is to use a single dose of a fast-acting or short-acting analgesic, usually 5% to 10% of the daily dose.
Patients with refractory sudden pain may be considered for patient-controlled drug pump dosing.
Bisphosphonate clinical application bisphosphonates can inhibit osteoclast-mediated bone resorption, prevent and treat SRE, and also inhibit the spread of tumor cell infiltration.
IV. Indications.
1, hypercalcemia.
2.Bone pain.
The main purpose of using bisphosphonates in breast cancer bone metastases is to reduce the incidence of SREs.
4.Before intravenous bisphosphonates or subcutaneous denosumab injection, plasma calcium concentration, creatinine, phosphorus and magnesium levels should be monitored. Since hypophosphatemia and hypocalcemia are likely to occur during treatment, it is recommended that calcium, phosphorus and magnesium levels should be monitored more closely during the treatment process.
5. Both bisphosphonate and denosumab treatment may cause osteonecrosis of the jaw. ONJ has an incidence of 3 per 1,000 in breast cancer patients. Risk factors for the occurrence of ONJ include the patient’s baseline oral health status and oral manipulation during treatment. Therefore, patients should be recommended to undergo dental examination before intravenous bisphosphonates or denosumab, and dental procedures during treatment should be avoided if possible.
6. Daily calcium and vitamin D supplementation should be given at doses of 1200~1500 mg/d of calcium and 400~800 U of vitamin D3 during long-term bisphosphonate combination therapy.
7.Add zoledronic acid, or ibandronic acid, or pamidronate disodium, or denosumab to the systemic treatment of breast cancer bone metastases once a month, or once every 3 months after 12 consecutive doses for those with stable disease. Most studies have shown that continuous administration for 1.5 to 2 years can significantly reduce the incidence of SREs.
8.After the first bone metastasis exacerbated by SREs during the use of a certain type of bisphosphonate, it is possible to consider switching to another type of bisphosphonate, but more evidence is needed to support this.
9, the following circumstances can be considered to discontinue: adverse reactions monitored during use and clearly associated with bisphosphonates; tumor deterioration during treatment, the emergence of other organ metastases and life-threatening; when clinicians think it is necessary. However, relief of bone pain after other treatments is not an indication for drug discontinuation.
10. For isolated bone metastases, the optimal timing and duration of administration of bone modulators has not been determined.