INVASIVE MICROPAPILLARY CARCINOMA OF THE BREAST OVEREXPRESSES MUC4 AND IS ASSOCIATED WITH POOR RESPONSE TO TRASTUZUMAB IN HER2-POSITIVE BREAST CANCER

MERCOGLIANO, MARÍA FLORENCIA; INURRIGARRO, GLORIA; DE MARTINO, MARA; VENTURUTTI, LEANDRO; RIVAS, MARTÍN ALFREDO; CORDO RUSSO, ROSALÍA; PROIETTI, CECILIA JAZMÍN; FERNÁNDEZ, ELMER A.; FIGURELLI, SILVINA; BARCHUK, SABRINA; GIL DEZA, ERNESTO; ARES, SANDRA; GERCOVICH, FELIPE G.; ELIZALDE, PATRICIA V.; SCHILLACI, ROXANA

CABA

Congreso; Reunión conjunta de sociedades de biociencias, LXII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Invasive micropapillary carcinoma of the breast (IMPC) is a low-frequent tumor variant (~6% of all breast cancers) characterized by an inside-out formation of tumor clusters surrounded by stroma with a pseudopapillary arrangement and it has a poor clinical outcome that does not correlate with the number of micropapillary features. Pathologists underreport IMPC because it is difficult to identify and there are no biomarkers available. HER2-positive breast cancers (HER2+ BC) have an aggressive behavior. This subtype is treated with trastuzumab (TZ) but 40-60% of the patients do not respond to therapy due to resistance. We recently demonstrated that TNFα-induced mucin 4 (MUC4, membrane glycoprotein that promotes metastasis dissemination) expression in HER2+ BC is a biomarker of poor prognosis to adjuvant TZ.Here we studied the clinical significance of IMPC and MUC4 expression in HER2+ BC patients.We retrospectively studied 86 HER2+ BC patients treated with TZ in the adjuvant setting. We explored the association between IMPC and clinicopathological parameters at diagnosis and its prognostic value.IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2+ cases. It was positively correlated with estrogen receptor expression and tumor size, but 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 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 (P