Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype

Abstract

The characteristics of brain metastases (BM) that develop after breast-conserving therapy (BCT) for early-stage breast cancer (BC) remain incompletely defined. We examined 1,434 consecutive patients with stage I/II invasive BC who received BCT from 1997 to 2006, 91% of whom received adjuvant systemic therapy, according to BC subtype. Median follow-up was 85months. Overall 5-year cumulative incidence of BM was 1.7%; 0.1% for luminal A, 3.3% for luminal B, 3.2% for luminal-HER2, 3.7% for HER2, and 7.4% for triple negative (TN). Women who developed BM were more likely at BC diagnosis to be younger (P<.0001) and have node-positive (P<.0001), grade 3 (P<.0001), hormone receptor-negative (P=.006), and HER2-positive (P=.01) tumors. Median time from BC diagnosis to BM was 51.4months (range, 7.6-108months), which was longer among luminal versus non-luminal subtypes (P=.0002; median, 61.4 vs. 34.5months). Thirty-four percent of patients who developed distant metastases (DM) eventually developed BM. Median time from DM to BM was 12.8months but varied by subtype, including 7.4months for TN, 9.6months for luminal B, and 27.1months for HER2. Eighty-one percent of all BM patients presented with neurologic symptoms. Median number of BM at diagnosis was two, and median BM size was 15mm, with TN (27mm) and luminal B (16mm) exhibiting the largest median sizes. In conclusion, the risk of BM after BCT varies significantly by subtype. Given the large size and symptomatic presentation among luminal B and TN subtypes, earlier BM detection might improve quality of life or increase eligibility for non-invasive treatments including stereotactic radiosurgery. Women with DM from these two BC subtypes have a high incidence of BM with a short latency, suggesting an ideal target population for trials evaluating the utility of MRI screening.