RESUMEN
BACKGROUND: Adherence to clinical practice guidelines improves outcomes for patients with breast cancer. However, their implementation may not be feasible in low- and middle-income countries. This study aimed to evaluate physicians' adherence, attitudes, and barriers towards the Colima Consensus, which is the Mexican national breast cancer clinical practice guideline. METHODS: A cross-sectional, 31-item survey was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants' characteristics, adherence, attitudes, and barriers. RESULTS: Of 439 respondents, 78% percent adhered to Consensus recommendations and 94% believed it was applicable to their clinical practice. Forty percent reported using the Consensus as their sole breast cancer guideline. This was associated with being a surgical oncologist (OR 3.3, 95% CI 2.0-5.3) and practicing at a public hospital (OR 2.1, 95% CI 1.2-3.7). The most common barriers to adherence were lack of resources and logistical problems. Regarding attitudes towards the Consensus, 90% considered it a good educational tool, 89% considered it a reliable source of information, and 90% thought it improved quality of care. CONCLUSIONS: We showed high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion of physicians using it as their only guideline. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local breast cancer guidelines and suggest a need for the creation of resource-stratified guidelines.
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Neoplasias de la Mama , Médicos , Humanos , Femenino , Neoplasias de la Mama/terapia , Estudios Transversales , México , Actitud del Personal de Salud , Adhesión a Directriz , Pautas de la Práctica en Medicina , Encuestas y CuestionariosRESUMEN
In triple-negative breast cancer (TNBC), only 30% of patients treated with neoadjuvant chemotherapy achieve a pathological complete response after treatment and more than 90% die due to metastasis formation. The diverse clinical responses and metastatic developments are attributed to extensive intrapatient genetic heterogeneity and tumor evolution acting on this neoplasm. In this work, we aimed to evaluate genomic alterations and tumor evolution in TNBC patients with aggressive disease. We sequenced the whole exome of 16 lesions from four patients who did not respond to therapy, and took several follow-up samples, including samples from tumors before and after treatment, as well as from the lymph nodes and skin metastases. We found substantial intrapatient genetic heterogeneity, with a variable tumor mutational composition. Early truncal events were MCL1 amplifications. Metastatic lesions had deletions in RB1 and PTEN, along with TERT, AKT2, and CCNE1 amplifications. Mutational signatures 06 and 12 were mainly detected in skin metastases and lymph nodes. According to phylogenetic analysis, the lymph node metastases occurred at an early stage of TNBC development. Finally, each patient had three to eight candidate driving mutations for targeted treatments. This study delves into the genomic complexity and the phylogenetic and evolutionary development of aggressive TNBC, supporting early metastatic development, and identifies specific genetic alterations associated with a response to targeted therapies.
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Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.
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Mutación , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/mortalidad , Adulto , Anciano , Trastornos por Deficiencias en la Reparación del ADN/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/patología , Persona de Mediana Edad , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Secuenciación del ExomaRESUMEN
The incidence of reported pseudoangiomatous stromal hyperplasia (PASH), as well as the variability and severity of clinical presentations, is increasing in the literature. In parallel, several authors posit the need for an improved classification of PASH to avoid possible variables associated with this diagnosis. Here, we present a 25-year-old woman with PASH accompanied by severe bilateral and symmetrical breasts enlargement, highlighting an uncommon clinical presentation of PASH as much as the careful interdisciplinary review and correlation of histology and all available imaging studies to confirm the definitive diagnosis.
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Human papillomavirus (HPV) has been implicated in breast carcinogenesis. Consecutive and non-selected mastectomy specimens from Mexican patients harboring breast carcinomas were sampled in order to look for the presence of HPV DNA. HPV-16 was detected in 6 (10%) of 60 breast carcinomas. Two of these also had HPV genome in adjacent non-neoplastic mammary-tissues. Seven cases had HPV DNA only in non-neoplastic tissue specimens. HPV DNA was also detected in 4 (25%) of 10 tumor-bed specimens without residual neoplastic lesions that were obtained from patients who underwent neoadjuvant chemotherapy or neoadjuvant chemotherapy/radiotherapy. HPV-positive tumors tended to be smaller in size, than HPV-negative tumors (p=0.047). Histological distributions of HPV-positive and -negative cases showed no significant difference. Although all the HPV-16 DNA were found integrated, its low viral load rendered it difficult to incriminate this virus in breast carcinogenesis. However, the possibility that HPV infection occurred during carcinoma development cannot be ruled out.
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Neoplasias de la Mama/virología , Carcinoma Ductal de Mama/virología , Carcinoma Lobular/virología , Carcinoma Papilar/virología , Papillomavirus Humano 16/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/epidemiología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/terapia , Carcinoma Papilar/epidemiología , Carcinoma Papilar/metabolismo , Carcinoma Papilar/terapia , Femenino , Humanos , Glándulas Mamarias Humanas/virología , México , Persona de Mediana Edad , Pezones/virología , Infecciones por Papillomavirus/epidemiología , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Carga ViralRESUMEN
Se describe el caso de una mujer de 77 años que presentó datos cerebrales de un probable carcinoma con primario de origen desconocido. En el estadio final de su evolución clínica presentó datos de abdomen agudo. Se efectúan consideraciones acerca del manejo de las neoplasias de origen desconocido que eventualmente dan metástasis a sistema nervioso central. Así mismo se presenta una revisión bibliográfica de las diferentes extirpes histológicas que metastatizan a cerebro y se comenta acerca de su pronóstico. Finalmente, se efectúan comentarios de los hallazgos histopatológicos.