BACKGROUND: Predictive factors of survival benefit from taxane over non-taxane based adjuvant chemotherapy regimens are needed. Recent studies have suggested that “intrinsic” breast cancer subtypes may differ in their responsiveness to specific chemotherapeutics. Tumor samples from GEICAM 9906 study (Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone [FEC] or FEC Followed by Paclitaxel [FEC-P] for Early Breast Cancer, JNCI 100:805, 2008) were gene expression profiled using the RT-qPCR PAM50 clinical test in order to identify potential predictive markers of taxane clinical benefit. METHODS: 793 formalin-fixed paraffin-embedded tumors were studied and classified into intrinsic subtypes (Luminal A & B, HER2−enriched, Basal-like, and Normal) using the PAM50 test. The assay also provided gene expression scores for the standard protein biomarkers usually measured by immunohistochemistry (ESR1/ER, PGR/PR, and ERBB2/HER2) and a meta-gene score for proliferation (proliferation signature) and for a luminal gene signature. Intrinsic subtypes, individual genes, or meta-genes were correlated with disease-free survival (DFS). Multivariable Cox regression analyses were performed to determine the significance of the interaction between treatment and intrinsic subtypes, single genes and meta-genes, adjusting for standard clinicopathological factors. RESULTS: A 8.7 years follow-up update of GEICAM 9906 trial confirmed a statistically significant advantage of FEC-P over FEC in terms of DFS (p=0.016) and OS (p=0.013). Exploratory analyses for prognostic factors showed that treatment arm (p=0.016), tumor size (p<0.0001), type of surgery (p=0.003), tumor grade (p=0.001), nodal status (p<0.0001), intrinsic subtypes (p<0.0001), ERBB2 (p=0.031), PGR (p<0.0001), Luminal meta-gene (p=0.006) and Proliferation meta-gene (p<0.0001) were associated with DFS. A Cox multivariate analysis using the backward and forward method showed that only the treatment arm (P=0.052), tumor size (p=0.0003), nodal status (p=0.001), intrinsic subtypes (p=0.045) and Proliferation (p=0.008) were prognostic for DFS. Concerning predictive factors, exploratory analyses were performed and interaction tests were calculated. Theses analyses showed that FEC-P was superior to FEC in low PGR expression (HR= 0.68, p=0.034) and not in high PGR group (HR=0.83, p=0.245); interaction test p=0.358. Similarly, FEC-P was superior in low ERBB2 expression (HR=0.67; p=0.005) and not in the high ERBB2 group (HR=0.92, P=0.707); interaction test p=0.256. Interestingly, superiority of FEC-P was observed for the low Proliferation Signature group (HR=0.58, p= 0.006) in contrast to the high proliferation group (HR=0.93, p=0.633); the interaction test showed an almost statistical significant difference (p=0.069). The FEC-P arm showed improved outcome in all genomic intrinsic subtypes, although no subtype alone reached statistical significance. CONCLUSION: Our study suggests that the PAM50 proliferation signature could be predictive of benefit for adding weekly paclitaxel to the adjuvant chemotherapy FEC regimen. These results need further validation in an independent study. The last two authors of this abstract have contributed equally to this study. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-04.
Background: The EndoPredict (EP) score is an RNA-based multigene test to predict the likelihood of distant recurrence in ER-positive (ER+), HER2-negative (HER2−) breast cancer (BC) patients treated with adjuvant endocrine therapy. Results from two large randomized phase III trials involving endocrine therapy only (n > 1700) demonstrated a prognostic power of the EP score beyond what can be achieved by combining the commonly used clinicopathological parameters (Filipits M, 2011). The performance of the EP in chemotherapy-treated patients has not been evaluated yet. Here, we analyzed the EndoPredict score in node-positive ER+/HER2− BC patients from the GEICAM-9906 trial, treated with adjuvant chemotherapy followed by hormonal therapy. Methods: Patients included in this study participated in the GEICAM/9906 trial and were either treated with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P) (Martin M, 2008). ESR1 and ERBB2 gene expression were assessed by qRT-PCR in 800 formalin-fixed paraffin embedded (FFPE) tumor samples out of 1246 patients included in the GEICAM/9906 trial. The EndoPredict score (including eight prognostic genes) was successfully determined in 555 out of the 566 ER+/HER2− patients. Patients were assigned into two categories (high/low), according to the predefined EP cut-off value (Filipits M, 2011). The primary endpoint for the analysis was distant metastasis. Metastasis rates were estimated using the Kaplan–Meier method. Multivariate analysis was performed using Cox regression. Interaction between treatment effects and EP was tested as well. Results: Twenty-five percent of patients (n = 141) were classified as EP-low-risk. Kaplan Meier analysis demonstrated that the metastasis-free survival (MFS) was 92% in the EP-low risk vs. 69% in the EP-high-risk group (absolute difference of 23%, HR 4.4 (2.3–8.4) p < 0.0001). Multivariate analysis showed that EP is an independent prognostic parameter after adjustment for age, grade, lymph node status and tumor size. EP was found to be prognostic in pre- (p = 0.0002, HR = 5.5 (2.2–13.6)) and postmenopausal (p = 0.0129, HR = 3.3 (1.3–8.2)) BC patients. There were not statistically significant differences in MFS between treatment arms (FEC vs. FEC-P) neither in the high nor in the low-risk groups. Interaction test between chemotherapy arm and EP score was not significant. Conclusions: The results of this study shows that the EndoPredict score is an independent prognostic parameter in node-positive, ER+/HER2− BC patients treated with adjuvant chemotherapy followed by hormonal therapy. EndoPredict was not found to be predictive of weekly paclitaxel efficacy. Novel predictive biomarkers are needed to identify the small subset of patients with ER+/HER2− tumors that actually benefit from weekly paclitaxel-containing regimens. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-11.
Endomyocardial fi brosis is a rare cause of restrictive cardiomyopathy which predominates in lowincome population living in tropical areas. It´s characterized by endomyocardial fi brous tissue deposition causing restrictive physiology with poor prognosis without proper management. We present a 40-yearold woman with right ventricular endomyocardial fi brosis complicated by pericardial effusion and a giant atrial thrombus. The use of multimodal imaging is very important for the diagnosis of this extremely rare pathology in our country.
Introduction: Classification by intrinsic subtypes by gene expression profiles of early-stage breast cancer (EBC) provides information of prognostic value and constitutes a tool to help in making therapeutic decisions. Several authors have proposed surrogated classifications based on immunohistochemistry results (IHC) in order to facilitate a classification with identical prognostic and predictive value. However, there is evidence that suggests a lack of correlation between these classifications. The aim of this study was to evaluate the correlation between classification by intrinsic subtypes in patients with EBC ER+/ HER2neg, obtained by PAM50 and the surrogated classification proposed by St. Gallen 2013. Methods: Samples from 12 centers from the spanish region of Castilla y León were analyzed by PAM50 (nCounterTM / Nanostring) at the University Hospital of Salamanca. The results obtained were compared with the surrogate classification of St.Gallen'13 from local reports. Tumors of patients pre and post-menopausal tests T1-2, N0-N1mi, grade I-II that met criteria for inclusion of the regional evaluation program through ProsignaTM were included. Results: Between August'15 and December'17, 264 samples were analyzed. All patients were classified by IHC as lum-A or lum-B. In total 113 cases were reclassified by PAM50 (43%). The change of LumA by IHC to Lum-B by PAM50 was 18%, while Lum-B by IHC to Lum-A by PAM50 was 58% (n = 89). In those cases considered Lum-B by IHC based only in a value of Ki67>14% (n = 93), 54% was reclassified to Lum-A. Conversely, when low expression (negative or <20%) of Progesterone Receptor (PR) was used as the single criterion of Lum-B by IHC (n = 44), PAM50 reclassified 33 cases as Lum-A (75%). Applying the Kappa test to analyze the concordance between the 2 tests, a coefficient of 0.203 (low agreement) was obtained, statistically significant (0.000). Conclusion: The surrogated classification by IHC of intrinsic subtypes in EBC ER+/HER2neg shows a low concordance with PAM50 analysis, and cannot be considered adequate. In particular, the presence of negative or <20% PR as the only criterion seems the least appropriate and should not be recommended for a surrogated classification of a tumor as Lum-B, overestimating the real risk of numerous patients. PAM50 allowed the reclassification in more than 40% of cases, especially csaes considered Lum-B by IHC. Citation Format: Rodriguez CA, Guillen C, Garcia M, Sancho M, Gomez A, Ludena D, Cruz JJ. Discordance between surrogated intrinsic subtypes defined by immunohistochemistry compared with PAM50 in ER positive / HER2 negative early breast cancer. Analysis of value of the status of the progesterone receptor and Ki67 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-07.
This abstract was withdrawn by the authors.
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