Survival in pregnancy-associated breast cancer patients compared to non-pregnant controls.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. METHODS: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. RESULTS: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). CONCLUSIONS: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.

Papel de p38 MAPK en los efectos de la inhibición de la biosíntesis de colesterol en la progresión del ciclo celular en la línea promielocítica humana HL-60 / Role of p38 MAPK in the effects of cholesterol biosynthesis inhibition on cell cycle progression in HL-60 cells

Introducción. El colesterol es necesario para la proliferación y la correcta progresión del ciclo celular. La inhibición sostenida de la biosíntesis de colesterol inhibe la citocinesis y da lugar a la aparición de células poliploides, efectos que pueden implicar la participación de las vías de estrés. Objetivo. Estudiar el efecto de la inhibición terminal de la biosíntesis de colesterol sobre la vía de p38 MAPK y su papel en la progresión del ciclocelular. Metodología. La inhibición de la biosíntesis de colesterol en las células promielocíticas humanasHL-60 se llevó a cabo con SKF 104976. En determinados casos, junto a este inhibidor, se inhibieron las vías de p38 MAPK y ERK1/2empleando SB 203580 y PD 98059,respectivamente. El ciclo celular se estudió por marcaje con yoduro de propidio e incorporación de bromodesoxiuridina y análisis por citometría de flujo, y la expresión de proteínas se analizó por Western blot. Resultados. La inhibición de la biosíntesis de colesterol produjo la acumulación de células enG2/M y una activación transitoria de p38 MAPK, efectos que fueron revertidos por las lipoproteínas de baja densidad (LDL), demostrando que se debían a la deficiencia de colesterol. En aquellas condiciones, la adición de SB 203580 aceleró la replicación del ADN acompañada de un aumento de la poliploidía. Contrariamente, la adición de PD98059 inhibió la síntesis de ADN. Ni la inhibición de p38 MAPK ni la de ERK impidieron la división de las células previamente tratadas con SKF104976 tras suplementarlas con LDL, ni de las células previamente sincronizadas en prometafase con nocodazol. Conclusiones. La inhibición de la biosíntesis de colesterol activa la vía de p38 MAPK a fin de impedir la poliploidía pero no tiene efecto sobre la culminación de la mitosis (AU)

Introduction. Cells require cholesterol for proliferation and correct progression of the cell cycle. In the absence of cholesterol, the cells fail tounder go cytokines is and polynucleated cells are generated. These effects could be mediated by stress signal transduction pathways. Objective. To study the effects of cholesterol biosynthesis inhibition on the activity of p38MAPK and to evaluate the role of this pathway on cell cycle progression. Methodology. Human leukemia cells (HL-60)were incubated in the presence of SKF 104976, an inhibitor of cholesterol biosynthesis. In some cases inhibitors of p38 MAPK and ERK1/2, namely SB203580 and PD 98059, were added to the medium. Cell cycle progression was studied by flow citometry, both DNA content and bromodeoxyuridine incorporation into DNA, and protein expression of p38 MAPK was analyzed by western blot. Results. Inhibition of cholesterol biosynthesis led to accumulation of cells in G2/M and a transient activation of p38 MAPK. These effects were reversed by supplementing the medium with LDL. The addition of SB 203580 accelerated DNA replication, which was accompanied by an increase of polyploidy. By contrast, the addition of PD98059 inhibited DNA synthesis. Lastly, neither the inhibition of p38 MAPK nor ERK affected the division of cells treated with the cholesterol biosynthesis inhibitor following LDL provision, or mitosis completion from metaphase of cells previously synchronized with nocodazole. Conclusions. Cholesterol deficiency induces p38MAPK pathway activation in order to prevent polyploidy, but has no effect on mitosis completion (AU)