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Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).
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OBJECTIVE: To assess independent prognostic factors described in the literature. Thus, to identify different risk groups. METHODS: Review of the records with a diagnosis of primary vulvar squamous cell carcinoma (January/1992-January/2012). INCLUSION CRITERIA: depth of stromal invasion (DSI) >1mm, pathological tumor size >2 cm, and pathological tumor-free margin ≥ 8 mm. Patients who underwent neoadjuvant therapy due to locoregionally advanced vulvar cancer were excluded. All the patients underwent radical, both local and regional, surgery. Adjuvant radiation therapy was administered to all patients with positive nodes. Features of lymph nodes, tumor size, age, grade, lymphovascular space invasion (LVSI), DSI, type of radical surgery, pathological margin distance and stage were evaluated by univariate and multivariate analysis. RESULTS: 194 patients were included. Median age: 67 years. Median follow-up: 62 months. 5-year OS and DFS: 65.5% and 58.2%. Positive lymph nodes were found in 91 (46.9%) patients. After a multivariate analysis, the number of positive lymph nodes, extra-nodal growth, pathologic tumor size and DSI proved to be independent prognostic factors. A high risk group for failure to survive (5y-OS 24%) was identified: tumor size ≥ 6-7.9 cm and DSI >4mm or ≥ 8 cm irrespective of DSI; and extra-nodal growth or ≥2 positive lymph nodes irrespective of tumor size and DSI. CONCLUSIONS: A new high-risk group was identified based on different cutoff values for tumor size, extra-nodal growth and number of positive lymph nodes. This could be very important in the tailored treatment of a specific group of patients with bulky primary tumors and a poorer prognosis.
