Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor response to trastuzumab in HER2-positive breast cancer

ROXANA SCHILLACI; FLORENCIA MERCOGLIANO; GLORIA INURRIGARRO; MARA DE MARTINO; LEANDRO VENTURUTTI; MARTIN RIVAS; ROSALIA INES CORDO RUSSO; CECILIA J PROIETTI; ELMER FERNANDEZ; ISABEL FRAHM; SABRINA BARCHUCK; DANIEL HORACIO ALLEMAND; SILVINA FIGURELLI; ERNESTO GIL DEZA; SANDRA ARES; FELIPE GERCOVICH; EDUARDO CORTESE; MATIAS AMASINO; PABLO GUZMAN; JUAN CARLOS ROA; PATRICIA V ELIZALDE

BMC CANCER

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2017

1471-2407

AbstractBackground: Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant of low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor-2 which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC.Methods: We retrospectively studied 86 HER-2-positive breast cancer patients treated with trastuzumab in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry.Results IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression, tumor size and inversely correlated with patient?s age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio= 2.6; 95%, confidence interval 1.1-6.1, P = 0.0340). MUC4, a glycoprotein associated with metastasis dissemination, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression with respect to IDC, lobular and mucinous carcinoma.Conclusion: In HER2-positive breast cancer the presence of IMPC should be carefully examined. As IMPC is often not informed, because it is relative difficulty to identify or directly overlooked, we propose MUC4 expression as a useful biomarker to highlight its presence. Patients with MUC4-positive tumors with IMPC component should require more frequent monitoring and/or more aggressive therapies.