Brain as site of first recurrence after adjuvant therapy for early breast cancer: pooled analysis of 7 sequential studies

Data on the risk factors that increase the risk of brain metastases (BM) in breast cancer are lacking. Mining the prospectively collected data of adjuvant studies for BM at first recurrence may identify a population for preventive strategies. Pooled analysis of data from 7 sequential adjuvant studies by the Hellenic Cooperative Oncology Group investigated recurrence in CNS. A total of 5318 early breast cancer patients were included. After a median follow-up of 137.0 months (range 0-334.1), the 120-month invasive breast cancer-free survival rate was 73.2% (95% CI 72.0-74.4) and the 120-month overall survival rate was 78.3% (77.2-79.4). A total of 106 patients (2%) developed BM at first recurrence, and of those, 68 (64.2%) had BM only. In cause-specific Cox models, triple-negative subtype (HR 3.43; 95% CI 2.05-5.75) and four or more positive axillary nodes (2.52; 1.47-4.33) were independently associated with BM at first recurrence; AJCC stage III (3.41; 1.56-7.44) and hormone receptor negativity (2.08; 1.37-3.15) remained independently associated in alternative parameterization. Triple-negative breast cancer patients had a higher cumulative incidence of BM at 120 months (3.86%) compared with luminal A/B disease (1.27%) with a steep rise in the early years after adjuvant therapy. BM patients had significantly worse survival from first recurrence than patients with extracranial first recurrence (median 8.0 versus 31.2 months; HR 2.66; 95% CI 2.15-3.29), with HER2-positive patients having significantly longer breast metastasis-specific survival than other subtypes (median 13.0 versus 5.4 months; HR 0.56; 95% CI 0.36-0.86). The authors conclude that BM seem to occur rarely at first recurrence but carry a poor prognosis.