Brain metastases remain an unmet clinical need in breast oncology, being frequently found in HER2-overexpressing and triple-negative carcinomas. These tumors were reported to be highly cancer stem-like cell-enriched, suggesting that brain metastases probably arise by the seeding of cancer cells with stem features. Accordingly, we found that brain-tropic breast cancer cells show increased stem cell activity and tumorigenic capacity in the chick embryo choriallantoic membrane when compared to the parental cell line. These observations were supported by a significant increase in their stem cell frequency and by the enrichment for the breast cancer stem cell (BCSC) phenotype CD44+CD24−/low. Based on this data, the expression of BCSC markers (CD44, CD49f, P-cadherin, EpCAM, and ALDH1) was determined and found to be significantly enriched in breast cancer brain metastases when compared to primary tumors. Therefore, a brain (BR)-BCSC signature was defined (3–5 BCSC markers), which showed to be associated with decreased brain metastases-free and overall survival. Interestingly, this signature significantly predicted a worse prognosis in lymph node-positive patients, acting as an independent prognostic factor. Thus, an enrichment of a BCSC signature was found in brain metastases, which can be used as a new prognostic factor in clinically challenging breast cancer patients.
BackgroundBrazil is a middle-income country with inequalities in its healthcare system. The disparities between public and private services affect the diagnosis and treatment of patients with breast cancer. The aim of this study is to assess whether disease-free survival (DFS) and overall survival (OS) are different in public and private specialized centers.Patient and methodsA retrospective cohort study with 1,545 breast cancer patients diagnosed from 2003 to 2011 at Barretos Cancer Hospital—BCH (public group, N = 1,408) and InORP Oncoclinicas (private group, N = 137) was conducted. A 1:1 propensity score matching (PSM) analysis was used to adjust the differences between the groups’ characteristics (n = 137 in each group).ResultsThe median age at diagnosis was 54.4 years. Estimated DFS rates at 1, 5, and 10 years were 96.0%, 71.8%, and 59.6%, respectively, at BCH and 97.8%, 86.9%, and 78%, respectively, at InORP (HR: 2.09; 95% confidence interval [CI], 1.41–3.10; p < 0.0001). Estimated OS rates at 1, 5, and 10 years were 98.1%, 78.5%, and 65.4%, respectively, at BCH and 99.3%, 94.5%, and 91.9%, respectively, at InORP (HR: 3.84; 95% CI, 2.16–6.82; p < 0.0001). After adjustment by PSM, DFS and OS results in 1, 3, and 5 years remained worse in the public service compared to the private service.ConclusionPatients treated in a public center have worse DFS and OS after a follow-up period of more than 5 years. These results were corroborated after carrying out the PSM.
e12105 Background: The best sequence of anthracyclines and taxanes in the neoadjuvant chemotherapy of HER2-negative breast cancer is still unknown. The aims of this study were to assess the impact of the sequence order in the pathological complete response (pCR) rate, and in the disease free survival (DFS) and overall survival (OS). Methods: We retrospectively reviewed 235 HER2-negative breast cancer women treated with neoadjuvant chemotherapy from 2003 to 2011 at our cancer center. The patients were pooled in two groups: anthracycline-based followed by taxanes (AC-T) and the reverse sequence (T-AC). The chi-square test was performed to verify the homogeneity between the groups and to compare pCR rate among the treatment groups. Cumulative survival probabilities were calculated using the Kaplan-Meier method. Differences between survivals were tested using the log-rank test. Results: The AC-T (n = 161) and T-AC (n = 74) groups were balanced for age, staging, receptor profile and histologic grade. The follow-up was at least five years for each patient. The median age was 50.1 years. Most patients (97%) had stage III tumors and 72 (30%) had triple negative disease. pCR rate was higher in triple negative compared with luminal cases (16.3 vs. 7.3%; p = 0.049). Treatment sequence did not influence the occurrence of pCR (10.5 vs. 8.5%; p = 0.8) or median survival times (DFS: 87.9 vs. 64.1, p = 0.85; OS: 91.1 vs. 71.6 months, p = 0.15), in the AC-T and T-AC groups, respectively. Conclusions: The sequence of neoadjuvant taxane-anthracycline-based chemotherapy regimen in daily practice did not show difference in the evaluated clinical outcomes. The retrospective design and the low number of patients may limit the power of the study to detect statistically significant differences. Phase III trials should be stimulated in this context. [Table: see text]
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