Concordance of genomic alterations between primary and recurrent breast cancer.

There is growing interest in delivering genomically informed cancer therapy. Our aim was to determine the concordance of genomic alterations between primary and recurrent breast cancer. Targeted next-generation sequencing was performed on formalin-fixed paraffin-embedded (FFPE) samples, profiling 3,320 exons of 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer. Point mutations, indels, copy-number alterations (CNA), and select rearrangements were assessed in 74 tumors from 43 patients (36 primary and 38 recurrence/metastases). Alterations potentially targetable with established or investigational therapeutics were considered "actionable." Alterations were detected in 55 genes (mean 3.95 alterations/sample, range 1-12), including mutations in PIK3CA, TP53, ARID1A, PTEN, AKT1, NF1, FBXW7, and FGFR3 and amplifications in MCL1, CCND1, FGFR1, MYC, IGF1R, MDM2, MDM4, AKT3, CDK4, and AKT2. In 33 matched primary and recurrent tumors, 97 of 112 (86.6%) somatic mutations were concordant. Of identified CNAs, 136 of 159 (85.5%) were concordant: 37 (23.3%) were concordant, but below the reporting threshold in one of the matched samples, and 23 (14.5%) discordant. There was an increased frequency of CDK4/MDM2 amplifications in recurrences, as well as gains and losses of other actionable alterations. Forty of 43 (93%) patients had actionable alterations that could inform targeted treatment options. In conclusion, deep genomic profiling of cancer-related genes reveals potentially actionable alterations in most patients with breast cancer. Overall there was high concordance between primary and recurrent tumors. Analysis of recurrent tumors before treatment may provide additional insights, as both gains and losses of targets are observed.

Removal of primary tumor improves survival in metastatic breast cancer. Does timing of surgery influence outcomes?

BACKGROUND: Resection of intact primary tumor is controversial in metastatic breast cancer patients. The aim of this study is to review the impact of surgical resection of primary tumor on overall survival and to assess the role of timing of surgery on survival rates. METHODS: 208 patients with metastatic breast cancer diagnosed between 1982 and 2005 in the Hospital Clinico of Valencia (Spain) were analysed. Exclusion criteria were age >80, PS 3-4, Charlson score 3 or follow-up < 90 days. 123 of these underwent surgery and 85 did not. In order to assess the role of timing, the "surgery" cohort was divided into two sub-groups: "before" (n = 78) or "after" (n = 45) diagnosis of disseminated disease. RESULTS: In the surgery group, patients underwent mastectomy with axillary dissection (82.9%), without axillary dissection (8.9%) and conservative surgery (8.1%). After a median follow-up of 29.68 months, median OS in the "surgery" and the "non-surgery" groups were, 40.4 and 24.3 months. Removal of the primary tumor therefore had a significant positive impact on survival rates (p < 0.001). Benefits of surgery were observed mainly in patients with visceral disease (p = 0.005); no statistical differences were found in those with bone disease (p = 0.79). Univariate analysis for overall survival (OS) identified surgery, performance status, clinical T stage, hormone receptors and number and type of metastases as variables that impacted on survival. In the multivariate test, only resection of primary tumor and estrogen receptors maintained statistical significance, surgery having a protective effect with an HR 0.52 (95% CI 0.35-0.77). No differences in survival were found between the two sub-groups according to the timing of surgery: "before" vs "after"(p = 0.996). CONCLUSIONS: Resection of primary tumor should be considered not only as a palliative or preventive strategy but also as an approach that possibly contributes to the control of the disease in selected patients.

Esperanza de vida en la población usuaria del IMSS. como indicador de la acción de la seguridad social / Life expectancy in an IMSS user population as an indicator of social security action

Se construyó una tabla de vida para la población usuaria del Instituo Mexicano del Seguro Social, Delegación Jalisco, con el fin de conocer la esperanza de vida (EV) en esa población, sus diferencias en cuanto a grupo etáreo, sexo y variaciones de tendencia. Fue utilizado el método abreviado de Reed y Merrel, con datos obtenidos de los certificados de defunción de 1996. Se calculó una EV al nacer de 76.36 años para hombres y 79.7 para mujeres, cifras superiores a la nacional (70.8 años) y a la de Jalisco (72.17 años). Es notable una mejoría en la EV general, hay un cambio positivo de 3.31 puntos respecto al año de 1983. Concluimos que nuestra población está al borde de una transición demográfica consumada, con un incremento del grupo de 20 a 64 años, y que se requiere adoptar los servicios a la nueva estructura de salud poblacional. Por ello, el equipo de salud deberá estrechar su labor participativa con la población, teniendo a la seguridad social como base de la promoción y cuidado de la salud