Impact of treatment response to neoadjuvant chemotherapy on brain metastasis patterns and breast cancer prognosis

Abstract

Background: Brain metastases (BM) are a major cause of mortality in breast cancer. While pathologic complete response (pCR) after neoadjuvant chemotherapy is associated with favorable survival outcomes, its impact on BM development and prognosis remains unclear. Methods: We retrospectively analyzed 1,244 patients with early-stage breast cancer who underwent neoadjuvant chemotherapy followed by surgery. Clinicopathological features, BM incidence, and survival outcomes were assessed. Propensity score matching (PSM) was applied to adjust for baseline differences. Gene expression profiling was performed in BM samples from pCR and non-pCR patients. Results: Of these, 437 (35.1 %) patients achieved pCR and 52 (4.2 %) developed BM. In TNBC, non-pCR patients had a significantly higher BM rate (9.2 % vs. 3.3 %, P = 0.026), whereas no differences were observed in other subtypes. Patients with BM who achieved pCR were more likely to present with single brain lesion (42.9 % vs. 10.5 %, P = 0.016), undergo craniotomy (71.4 % vs. 31.6 %, P = 0.010), and less frequently had extracranial metastases (28.6 % vs. 73.7 %, P = 0.003). Median overall survival after BM was longer in the pCR (42 vs. 4 months, P = 0.002), and this benefit remained significant after PSM (43 vs. 10 months, P = 0.033). Transcriptomic analysis identified distinct molecular profiles, with upregulation of RPL27A and CTLA4 in pCR BM and non-pCR BM. Conclusions: pCR was associated with lower metastatic burden and improved survival following BM diagnosis. Molecular differences between pCR and non-pCR BM suggest distinct mechanisms of metastatic evolution, suggesting the need for tailored surveillance and preventive strategies.