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

MERCOGLIANO MF; INURRIGARRO G; DE MARTINO M; VENTURUTTI L; RIVAS MA; CORDO RUSSO RI; PROIETTI CJ; FERNANDEZ E; FIGURELLI S; BARCHUK S; GIL DEZA E; ARES S; GERCOVICH F; ELIZALDE PV; SCHILLACI R

Buenos Aires

Congreso; LXII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2017

Sociedad Argentina de Investigaciones Clinicas

Invasive micropapillary carcinoma of the breast (IMPC) is a low-frequenttumor variant (~6% of all breast cancers) characterized by aninside-out formation of tumor clusters surrounded by stroma witha pseudopapillary arrangement and it has a poor clinical outcomethat does not correlate with the number of micropapillary features.Pathologists underreport IMPC because it is difficult to identify andthere are no biomarkers available. HER2-positive breast cancers(HER2+ BC) have an aggressive behavior. This subtype is treatedwith trastuzumab (TZ) but 40-60% of the patients do not respondto therapy due to resistance. We recently demonstrated that TNFα-induced mucin 4 (MUC4, membrane glycoprotein that promotesmetastasis dissemination) expression in HER2+ BC is a biomarkerof poor prognosis to adjuvant TZ.Here we studied the clinical significance of IMPC and MUC4expression in HER2+ BC patients.We retrospectively studied 86HER2+ BC patients treated with TZ in the adjuvant setting. We exploredthe association between IMPC and clinicopathological parametersat diagnosis and its prognostic value.IMPC, either as a pure entity or associated with invasive ductalcarcinoma (IDC), was present in 18.6% of HER2+ cases. It waspositively correlated with estrogen receptor expression and tumorsize, but inversely correlated with patient?s age. Disease-free survivalwas significantly lower in patients with IMPC (hazard ratio= 2.6;95%, confidence interval 1.1-6.1, P = 0.0340). MUC4 was stronglyexpressed in all IMPC cases tested. IMPC appeared as the histologicalbreast cancer subtype with the highest MUC4 expression withrespect to IDC, lobular and mucinous carcinoma (P