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Preoperative CA 15.3 and prognosis in primary breast cancer

CA 15.3 preoperatorio en el pronóstico del cáncer de mama primario

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Abstract

CA15.3 is a breast cancer-associated antigen encoded by the MUC-1 gene. The clinical applications of CA 15.3 are the monitoring of response in advanced breast carcinoma and the early detection of recurrences. We have investigated the prognostic value of CA 15.3 in primary breast cancer. Preoperative serum CA 15.3 was measured in 478 patients with early breast cancer. Positive CA 15.3 was defined as > 30 U/ml. CA 15.3 positivity was correlated with patient outcome in terms of disease-free survival (DFS). Seven per cent of patients had elevated serum CA 15.3. A positive association was found between CA 15.3 positivity and tumour size. Twenty-one per cent of the patients with T3 and T4 tumours had high serum concentrations of CA 15.3; while only six per cent of patients with T1 and T2 tumours had elevated concentrations of CA 15.3 (p < 0.0001). There was no correlation between CA 15.3 serum levels and menopausal status, axilary lymph node status, estrogen receptor status, p53 and erbB-2 status, and CEA serum levels. With a median follow-up of 24 months, we found that elevated CA 15.3 levels predicted a poor clinical outcome. The probability of disease-free survival at two years was 73% in patients with high preoperative CA 15.3 compared with 90% in patients with normal CA 15.3 levels (logrank p = 0.003). The association of CA 15.3 with DFS was also analysed with a Cox analysis, and was found to be independent of tumour size. The multivariate analysis showed that poor disease-free survival was significantly associated with high CA 15.3 (p = 0.04), large tumour size (p = 0.001), estrogen receptor negative status (p = 0.008), overexpression of erbB-2 (p = 0.04), and overexpression of p53 protein (p = 0.03).

Preoperative serum CA 15.3 is significantly related to clinical outcome in patients with early breast cancer. High CA 15.3 indicates a poor prognosis and this is independent from tumour size. Whether the poor prognosis associated with CA 15.3 is related with the role of mucins in the adhesion of cancer cells needs to be investigated.

Resumen

El CA 15.3 es un marcador tumoral, producto del gen MUC-1, utilizado para la monitorización del tratamiento en cáncer de mama avanzado y la detección precoz de las recurrencias. Este estudio ha explorado el valor del CA 15.3 en el pronóstico del cáncer de mama primario.

Se determinaron los niveles séricos preoperatorios de CA 15.3 en el suero de 478 pacientes con cáncer de mama primario, correlacionándolos con la evolución de las pacientes, evaluada en términos de supervivencia libre de enfermedad.

Un 7% de las pacientes presentó elevación de CA 15.3 en el suero (> 30 U/ml). La elevación preoperatoria de CA 15.3 se correlacionó de manera muy significativa con el tamaño tumoral. El 21% de los pacientes con tumores T3 y T4 presentaron niveles elevados de CA 15.3, frente al 6% en el grupo de pacientes con tumores T1 y T2 (p < 0,0001). No hallamos correlación entre los niveles de CA 15.3 y el estado menopáusico, la afectación ganglionar axilar, la expresión en tejido tumoral de receptores estrogénicos, p53, o erbB-2, ni con los niveles séricos de CEA.

Los niveles elevados de CA 15.3 fueron un factor pronóstico desfavorable. Las pacientes con niveles altos de CA 15.3 tuvieron una supervivencia libre de enfermedad (SLE) significativamente peor que las pacientes con niveles normales de CA 15.3. A los 2 años la estimación de SLE era del 73% en las pacientes con CA 15.3 positivo y del 90% en las CA 15.3 negativo (log-rank, p = 0,03). El CA 15.3 tuvo, además, un valor pronóstico independiente en el análisis multivariante. El análisis de Cox de la SLE mostró la significación estadística de CA 15.3 elevado (p = 0,04) y de los siguientes factores: tamaño tumoral mayor (p = 0,001), receptores estrogénicos negativos (p = 0,008), sobreexpresión de erbB-2 (p = 0,04), y acÚmulo de p53 (p = 0,03).

La determinación preoperatoria de los niveles de CA 15.3 tiene valor pronóstico en las pacientes con cáncer de mama primario, y puede representar un factor de selección para tratamientos específicos dirigidos contra la mucina MUC-1.

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Correspondence to Ramón Colomera.

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Tornamiraa, M.V., Monteroa, S., Vargasb, C. et al. Preoperative CA 15.3 and prognosis in primary breast cancer. Rev Oncología 2, 316–319 (2000). https://doi.org/10.1007/BF02979595

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Key words

  • CA 15.3
  • breast carcinoma
  • disease-free survival
  • prognosis
  • mucin
  • MUC-1

Palabras clave

  • CA 15.3
  • cáncer de mama
  • supervivencia libre de enfermedad
  • pronóstico
  • mucina
  • MUC-1