RESUMEN
Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. Our retrospective study shows our experience with NGS of 324 genes in combination with protein expression in patients with advanced breast cancer (aBC). The primary purpose was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Between April 2018 and September 2019, 41 patients with aBC were offered a NGS test. The test was used to detect clinically relevant genomic alterations and to support further targeted therapy decisions. Hormone receptors, ERBB2 of tumors and PD-L1 was stained by immunohistochemistry. The data was recorded up to September 2019. After prior consent 41 results were available for further analysis. The most common BC subtypes were triple-negative (n = 16), HR+/ERBB2- (n = 15), and ERBB2+ (n = 9), with one missing data of the primary tumor. 27 patients had more than one genetic alteration. The most common alterations were PIK3CA (n = 14) and ERBB2 alterations (n = 11). Followed by ESR1 (n = 10), FGFR1 (n = 7) and PTEN (n = 7). 68% of the alterations were clinically relevant (tier I and II of ESCAT classification). The most common treatment recommendation was ERBB2-directed therapy (single or double blockade, trastuzumab emtansine and lapatinib) followed by alpelisib in combination with fulvestrant. Comprehensive genomic profiling combined with protein expression analysis in aBC allowed a guided personalized therapy for half of our patients. So far there are no well-defined tools allowing interpretations of genomic alterations detected by NGS in combination with protein expression and other factors.
Asunto(s)
Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de Neoplasias/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Fosfatidilinositol 3-Quinasa Clase I/genética , Receptor alfa de Estrógeno/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Persona de Mediana Edad , Mutación/genética , Proteínas de Neoplasias/genética , Receptor ErbB-2/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Estudios RetrospectivosRESUMEN
OBJECTIVE: The present study reviews our 5-year results with extensive, multivisceral cytoreduction in patients with FIGO stages IIIC and IV ovarian cancer. METHODS: During the five-year period from January 1995 to December 1999, 101 patients with primary epithelial ovarian cancer FIGO stages IIIC and IV had extensive multivisceral cytoreductive surgery at our department. Patients' history, surgery data, staging, recurrence and survival data were abstracted from the patients' records. RESULTS: Eighty-four (83%) patients had no gross residual disease after the complete surgical procedure. Mean follow-up was 46 months (range, 1-130). Eight patients died within 6 months postoperatively. Seventy-six of our one hundred one patients (75%) had disease progression or recurrence after a mean of 28 months (range, 4-110). Seventeen (17%) patients are alive without disease. Median survival was 47 months and five-year survival was 33% for all 101 patients. CONCLUSION: This series indicates that in the majority of patients with advanced ovarian cancer, primary surgery can lead to complete gross cytoreduction with substantial subsequent rates of disease-free and overall survival.
