Palliation in advanced triple-negative breast cancer: brain, bone, pleura, skin and end of life

Brain metastases occur in about 29 percent of patients with metastatic triple-negative disease in a 433-patient single-centre series (cumulative incidence 17 percent at one year and 25 percent at two; median survival 7.3 months after diagnosis), and in the KEYNOTE-522 RCB analysis more than half of relapses after a pathological complete response or minimal residual disease were in the central nervous system. Local treatment follows the general breast cancer rules: stereotactic radiosurgery for a limited number of lesions, surgery for a large symptomatic lesion, whole-brain radiotherapy for widespread disease, with dexamethasone for oedema. Drug activity in the brain is emerging rather than proven: in ASCENT (12 percent of patients had stable brain metastases) progression-free survival was numerically longer with sacituzumab govitecan but overall survival was similar to chemotherapy; a 26-patient German real-world series found an intracranial disease control rate of 42 percent with sacituzumab govitecan and 88 percent with trastuzumab deruxtecan; and the DEBBRAH trial reported a median overall survival of 13.3 months with trastuzumab deruxtecan in seven patients with HER2-positive or HER2-low leptomeningeal disease. TUXEDO-4 (trastuzumab deruxtecan, HER2-low, active brain metastases) is recruiting.

Bone metastases are less common than in hormone-receptor-positive disease but are treated the same way: single-fraction palliative radiotherapy for pain, denosumab or zoledronic acid to reduce skeletal events, urgent imaging and radiotherapy or surgery for spinal cord compression. Malignant pleural effusion is drained, with talc pleurodesis or an indwelling pleural catheter for recurrence. Chest wall and skin recurrence, more frequent in triple-negative disease, is treated with radiotherapy and wound care. Hand-foot syndrome (73 percent of patients on capecitabine in CREATE-X), neutropenia and diarrhoea (grade 3 or higher in 51 and 10 percent on sacituzumab govitecan in ASCENT), stomatitis and eye symptoms (datopotamab deruxtecan) and interstitial lung disease (12.1 percent any grade, 0.8 percent fatal with trastuzumab deruxtecan in DESTINY-Breast04) are the drug toxicities that most often need supportive management. Early integrated palliative care is recommended by the ESMO metastatic breast cancer guideline; there is no triple-negative-specific supportive care trial.