Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

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).

An analysis of reported independent prognostic factors for survival in squamous cell carcinoma of the vulva: is tumor size significance being underrated?

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.

Tailoring the treatment of locally advanced squamous cell carcinoma of the vulva: neoadjuvant chemotherapy followed by radical surgery: results from a multicenter study.

OBJECTIVE: To determine the feasibility of performing neoadjuvant chemotherapy (NCH) followed by radical surgery in patients with locally advanced squamous cell carcinoma of the vulva. METHODS: Prospective and multicenter trial. Thirty-five patients with a diagnosis of previously untreated locally advanced squamous cell carcinoma of the vulva were given 4 schemes of cisplatin-based NCH and 1 NCH regimen with single bleomycin. Then, they underwent radical surgery of the vulva if clinical response was 50% or more. Age, NCH schemes used, toxicity, response to treatment, type of radical surgery performed, and clinical outcome were evaluated. RESULTS: Thirty-three patients completed the proposed schemes, and 30 were assessed for radical surgery. Finally, 27 patients underwent radical surgery (radical vulvectomy or radical local excision plus bilateral inguinofemoral lymphadenectomy). In 2 cases of persistent rectal involvement, posterior pelvic exenteration was performed. Moreover, 24 of 27 patients remain with no evidence of disease to date. Toxicity was acceptable. Median age was 62 years (range, 54-72 years). Median follow-up was 49 months (range, 4-155 months). CONCLUSIONS: The use of NCH in selected groups may increase surgical feasibility in initially inoperable patients, thus favoring organ preservation and less extensive resections. Adverse reactions were acceptable, and vulvoperineal deleterious effects that may occur after radiotherapy were consequently avoided.

Alcances de la tomografía computada con alta resolución en la patología pulmonar con correlación histopatológica / Computed tomography using high resolution in pulmonary pathology and its histopathology correlation

Se presentan los resultados de la evaluación de 980 pacientes utilizando Tomografía Computada con alta resolución (TCAR), demostrando que los cortes obtenidos son equivalentes a la superficie de corte macroscópica de la anatomía patológica. Se realizan como mínimo 3 cortes fijos en los exámenes de rutina. Se hace una revisión y puesta al día de la patología observada manteniendo la división técnica en patrones pulmonares, correlacionándolos con la histopatología. Se presenta un nuevo enfoque en la interpretación del criterio de los tumores. Se propone la utilización sistemática de esta metodología en todos los procesos pulmonares focales y difusos

Alcances de la tomografía computada con alta resolución en la patología pulmonar con correlación histopatológica / Computed tomography using high resolution in pulmonary pathology and its histopathology correlation

Se presentan los resultados de la evaluación de 980 pacientes utilizando Tomografía Computada con alta resolución (TCAR), demostrando que los cortes obtenidos son equivalentes a la superficie de corte macroscópica de la anatomía patológica. Se realizan como mínimo 3 cortes fijos en los exámenes de rutina. Se hace una revisión y puesta al día de la patología observada manteniendo la división técnica en patrones pulmonares, correlacionándolos con la histopatología. Se presenta un nuevo enfoque en la interpretación del criterio de los tumores. Se propone la utilización sistemática de esta metodología en todos los procesos pulmonares focales y difusos

Efectos de la heparina en la microcirculación durante la sepsis en ratas / Heparine action over the microcirculation in septic rats

Se realizó un estudio comparativo entre dos grupos de ratas con peritonitis, con el objeto de relacionar la acción de la heparina en la difusión de la sepsis y sus acciones sobre la microcirculación. El modelo experimental fue ciego desvascularizado y perforado. Se realizaron cortes histológicos de riñón, pulmón, corazón, higado y suprarrenales, observándose en las ratas no heparinizadas peritonitis difusa y trombosis en la microcirculación con gérmenes. En el grupo de ratas heparinizadas se observaron abscesos bien delimitados en la cavidad con menor impacto funcional en los diferentes parénquimas. No se observó en este grupo fenómeno de coagulación intravascular diseminada

Efectos de la heparina en la microcirculación durante la sepsis en ratas / Heparine action over the microcirculation in septic rats

Se realizó un estudio comparativo entre dos grupos de ratas con peritonitis, con el objeto de relacionar la acción de la heparina en la difusión de la sepsis y sus acciones sobre la microcirculación. El modelo experimental fue ciego desvascularizado y perforado. Se realizaron cortes histológicos de riñón, pulmón, corazón, higado y suprarrenales, observándose en las ratas no heparinizadas peritonitis difusa y trombosis en la microcirculación con gérmenes. En el grupo de ratas heparinizadas se observaron abscesos bien delimitados en la cavidad con menor impacto funcional en los diferentes parénquimas. No se observó en este grupo fenómeno de coagulación intravascular diseminada

Pólipos rectocolónicos: diagnóstico, tratamiento, revisión histológica y deguimiento / Rectocolonic polyps: diagnosis, treatment, histologic review and follow-up

Se efectúa un estudio restrospectivo sobre 499 pólipos rectocolónicos extirpados entre 1976 y 1989. Se tuvo en cuenta edad, sexo, localización topográfica, tamaño y forma e histología de pólipos extirpados. Se reexaminaron histológicamente 303 especímenes, ya que se descartaron 147 pólipos hiperplásicos y 49 por tratarse de material no aprovechable. La revisión histológica mostró importantes diferencias con el exámen primitivo. En los adenomas tubulares disminuyó la displasia moderada de 9,7 a 4,5%. No se halló displasia severa en este grupo. En los tubulovellosos se redujo la displasia severa de 6,3 a 3,1%. En 3 casos se halló seudoinvasión carcinomatosa en este grupo y también se encontró un carcinoma focal contra 3 hallazgos de invasión neoplásica en el estudio anterior. En los adenomas vellosos aumentaron las displasias leves y disminuyeron las severas. De los 15 pólipos informados como vellosos con adenocarcinoma se ocluyeron seis, 3 por seudoinvasión y 3 como afectados por displasia moderada. Se destacan los hallazgos de la revisión que mostró las mayores diferencias en las lesiones de alto grado de riesgo y la tendencia a una disminución en ese grado

Pólipos rectocolónicos: diagnóstico, tratamiento, revisión histológica y deguimiento / Rectocolonic polyps: diagnosis, treatment, histologic review and follow-up

Se efectúa un estudio restrospectivo sobre 499 pólipos rectocolónicos extirpados entre 1976 y 1989. Se tuvo en cuenta edad, sexo, localización topográfica, tamaño y forma e histología de pólipos extirpados. Se reexaminaron histológicamente 303 especímenes, ya que se descartaron 147 pólipos hiperplásicos y 49 por tratarse de material no aprovechable. La revisión histológica mostró importantes diferencias con el exámen primitivo. En los adenomas tubulares disminuyó la displasia moderada de 9,7 a 4,5%. No se halló displasia severa en este grupo. En los tubulovellosos se redujo la displasia severa de 6,3 a 3,1%. En 3 casos se halló seudoinvasión carcinomatosa en este grupo y también se encontró un carcinoma focal contra 3 hallazgos de invasión neoplásica en el estudio anterior. En los adenomas vellosos aumentaron las displasias leves y disminuyeron las severas. De los 15 pólipos informados como vellosos con adenocarcinoma se ocluyeron seis, 3 por seudoinvasión y 3 como afectados por displasia moderada. Se destacan los hallazgos de la revisión que mostró las mayores diferencias en las lesiones de alto grado de riesgo y la tendencia a una disminución en ese grado